Neurociências Cognitivas

COGNITIVE NEUROSCIENCES

❖ Definition
 Cognition: the process of knowing (what arises from awareness, perception, and
reasoning)
 Neuroscience: the study of how the nervous System is organized and works
❖ Objective
 To understand the relationship between neural structure and function and how
cognition and behaviour emerge from the neural processing infrastructure.

RESEARCH IN COGNITIVE NEUROSCIENCE

❖ To achieve this objective, we might consider 3 main steps:

 Adequately describe the structure of brain
▪ E.g., Brodman’s areas 44 and 45 in the frontal lobe, known as the Broca’s
area.
 Have a framework for conceptualizing brain function
▪ E.g., one of the brain functions is the speech production which is associated
to the Broca’s area
 Be able to measure relevant neurophysiological events and adequately characterize
and conceptualize behaviour (take electrophysiological measures while a person is
reading aloud – speech production – and observe what is happening at brain level
while it occurs)
▪ E.g., we could install an EEG cap to a person and as him/her to perform a
reading aloud task. In this kind of tasks, we could observe for instance the
N170 ERPs component, and ERP component associated to words processing.

❖ The brain is non-linear, non-stationary system with adaptable processing elements

interconnected in a highly parallel and non-homogeneous network topology.
 Continued reductionism and atomization will probably not, on its own, lead to a
fundamental understanding of the system.
▪ Non-linear:
▪ Non-stationary: its characteristics and measures don’t remain constant over
time
▪ Adaptable elements: the elements forming part of a network can change
because of the experience, or because of special necessities. So, these
elements are not immutable.
▪ Interconnected and non-homogeneous: the distribution of the connections is
highly parallel and does not follow a homogeneous topology.

BASIC PRINCIPLES IN NEUROSCIENCES

❖ Leo Gerlach
 He proposed the Information Hopping Theory.
❖ Santiago Cajal
 He is known as the father of Neurosciences.
 In 1888 he proposed the Neuronal Theory and defended the Neuronism.
▪ Cajal defended the neuronal theory in which neurons represent individual
and independent structures although they are closely interconnected.
 He confirmed for the first time that the nervous system and the brain tissue are
formed by independent cells, the neurons.
❖ Camillo Golgi
 He discovered the silver nitrate method of staining nerve tissue.

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 He defended another view about the structure of the nervous system, the
Reticularism.
▪ Golgi defended that the nervous system had a reticular structure, there were
not individual cells on it as it happens in other tissues. He posited that
neurons were all connected through their extensions.

▪ Today we know that Cajal’s postulates were true.

Cajal’s Principles

1. Neuronal Theory
 Neurons are independent and autonomous units – morphology and functioning - that
are fleetingly connected to each other to transmit signals.
▪ Synapses: communication between neurons.
2. Principle of dynamic polarization
 In the nervous system, neurons conduct in only one direction. The signals are received
on the dendritic tree and the soma, and the responses are sent through the axons.
▪ Exceptions: antidromic conduction, ganglionic neurons an amacrine neurons.
▪ The connections specificity allows us to understand the organization and
development of the nervous system and the recovery patterns after brain
injuries
3. Principle of connectional specificity
 Neurons connect to each other in a specific, non-random way to achieve effective
networks.

NERVOUS SYSTEM ORGANIZATION

❖ Our organism has a complex system – the nervous system - which is not only able to control
the vital functions but also to perceive, remember, feel, organize, and generate movements
and responses depending on the information that we get from the environment.

❖ From an anatomic point of view, the nervous system is divided in two subsystems: the central
nervous system and the peripherical nervous system.
 Central Nervous System
▪ Encephalon: brain, cerebellum, brainstem
▪ Spinal Cord
• Characteristics:
o Protected by membranes, meninges - dura mater,
arachnoid, pia mater
o Protected by bone structures – skull and backbone
o Their organs have cavities (ventricles and ependymal ducts)
filled with cerebrospinal fluid: exchange of substances,
waste removal system, ionic balance, oxygen and glucose
transport, mechanical dumper system – blood-brain barrier
 Peripheral Nervous System
▪ Formed by nerves and neurons outside the central nervous system
• Characteristics:
o Not protected by membranes, bone structures or blood-
brain barrier

Types of Tissues in the Nervous System

❖ There are two types of tissues in the nervous system: the grey and the white matters.

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 The distribution of the grey and white matter is different in the brain and in the spinal
cord. In the brain grey matter is allocated outwards and the white matter in the
internal regions while in the spinal cord it is just the opposite, the grey matter is
allocated inwards and the white matter outwards.
▪ The grey matter is composed by cell bodies, dendrites, axon terminals,
neuronal synapses, and glial cells. Its function is to integrate information and
generate the nerve impulse. It is in the brain cortex, cerebellum and nuclei
inside the brain and spinal cord.
▪ The white matter is mainly formed by myelinated axons (white colour) and
its function is to conduct the nerve impulse.

Nervous System Functions

❖ Sensitive
 Internal
▪ Produces glandular secretions and organs regulation
 External
▪ Produces sensations according to colours, smells, temperature
❖ Integrative
 Analyses the information received and make decision which are visible in our
behaviour
❖ Motor
 Produces muscle contractions to generate the movement

❖ From the functional point of view, the nervous system can also be divided in two subsystems:
 Somatic Nervous System
▪ Consists of all CNS and PNS structures in charge of conducting conscious and
unconscious afferent information (sensitive) from the sensory receptors to
the CNS and in charge of carrying motor control information to the skeletal
muscles.
 Autonomic or vegetative Nervous System
▪ Is the part of out NS in charge of controlling our involuntary actions. It can act
on blood vessels, smooth muscle, and glands.
• Parasympathetic Nervous System
o Composed by fibres belonging to cranial nerves from the
brainstem and spinal nerves from the sacral region
o It is responsible of organs regulation when the body is at
rest
• Sympathetic Nervous System
o Composed by 23 ganglions located along and on both sides
of the spinal cord
o It acts in case of emergency (mobilizes the body for short-
term emergencies). It mediates the hormonal stress
response, increases the frequency of the heartbeat, dilates
the bronchi and pupils, and stimulates the suprarenal
glands.

o Both divisions act in a parallel way.

▪ However, the physiological influences are opposed.
o Both divisions use different paths
▪ Parasympathetic division: preganglionic axons
originate in the brainstem and the inferior
segments of the spinal cord.

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▪ Sympathetic division: preganglionic axons originate

in the middle third of the spinal cord.

BRAIN

❖ The brain is responsible for directing everything we do (voluntary or involuntary).

 The brain is mainly composed by water.
 It weights between 1.3 and 15kg (2% of the corporal weight).
 It consumes a lot of oxygen and energy (20% of the body energy).
 After interrupting the blood flow to the brain, we become unconscious in 8-10
seconds.
 The mean number of neurons is 1011.
 The mean number of synapses is 1014.
 It is formed by two hemispheres which are symmetric but not identical.
 The corpus callosum is fibres bundle which connect the right and the left hemispheres

Brain Vision Evolution

❖ First, researchers were mainly interested in presenting anatomical division of the brain.
 This vision evolved as more importance was given to brain functions and the limits of
the areas established by Brodmann became more diffuse due to the brain plasticity. In
this way, the functional divisions started to appear.

❖ Anatomical Vision
 Based on cytoarchitecture
 The main example is the division presented by Brodmann in 1903
▪ Brodmann performed a histological-topographic mapping of the brain
surface, he numbered areas from 1 to 52 – we still use this anatomical
mapping (e.g., areas 44 and 45 form the Broca’s area)
❖ Functional Vision
 Based on the connectivity of the brain and the plasticity of the synaptic connections
 The main example is the Penfield’s Homunculus which is based on cortical stimulation
 The size of the body parts is proportional to the complexity of the movements the
body parts can do.

Brain Hemispheres

❖ Our brain is divided in two parts: the left and the right hemispheres.
 Each hemisphere controls different functions.
 Both hemispheres are connected by the corpus callosum.
 The right hemisphere controls the left part of our body, and the left hemisphere
controls the right side. So, brain control is contralateral.

Cortex

❖ From an evolutionary point of view, is the newest layer of the brain.

 Its thickness is about 2 mm.
 It’s responsible for integrating all the cognitive capabilities - thanks to this structure
we can be conscious, to stablish relations and to perform complex reasonings.

❖ Structure
 In most of its surface, the cortex has 6 layers (isocortex)
 The hippocampus and the olfactory cortex have only 3 or 4 layers (allocortex).
 The cortex is distributed in columns and each column acts as an operating unit.

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❖ Neuronal cell types in the cortex

 The isocortex is mainly formed by two types of neuronal cells, pyramidal and
interneurons.
▪ Pyramidal neurons projection cells characterized by having dendritic spines
and having excitatory function. They transmit to other nerve centres the
results of the local computation in the operating unit (in the cortex column)
▪ Interneurons: there are different types of interneurons.
• The most important are the stellate cells, their axons are highly
branched within the columns, they can even change between layers
and have an excitatory function.
o Stellate cells have also dendritic spines as the pyramidal
neurons
• The rest of the subtypes do not have dendritic spines and perform
an inhibitory function (25% only), fusiform, horizontal, basket cell,
etc.

❖ Cortex connectivity
 The dendritic spines increase the surface of neuronal contact to stablish synapses.
 The pyramidal neuron axons stablish horizontal and oblique connections with other
cortex neurons to form neuronal networks.
▪ The pyramidal neurons in the layer V have a subcortical projection, which
means that they are the cortex exit door to other nervous centres in the
brain.
 The stellate neurons together with other types of interneurons processes basic
information within a column.

 The afferent signals (incoming signals) getting to the cortex can be divided in:
▪ Specific afferences: bring information from outside the cortex.
▪ Corti-cortical afferences: connect different cortical areas. Can be ascending
or descending
▪ Fuzzy afferences: procced from different regions of the brain and project in a
fuzzy way without columnar specificity.

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NERVOUS SYSTEM DEVELOPMENT

❖ We are born with neurons but very few connections.

 Biologic systems and neural connections are stablished through life as a function of
the individual experiences and learning procedures.
 So, our experiences model our nervous system since the very beginning. And therefore
we are all different, we are all born with neurons (at this point we are very similar) but
we will be unique because only we experience the life how we do, and this will make
us different from the others.

❖ During the embryonic stage, the brain generates much more neurons than needed later.
 Experience and behaviour will reinforce and stablish connections
 Some are reinforced and other become weaker (disappear)
 Everything is determined by the personal experience
 A re-entrance mechanism will reinforce the connections between the groups of
neurons already connected and this will form first local maps and then, global maps.
▪ This process constitutes the base for the formation of mental images in the
brain.

❖ Fertilization of the egg is followed by a series of events that lead to the formation of a
multicellular blastula, which has already begun to specialize.
 The blastula contains three main cell lines that, after a few days, form three layers.
▪ The ectoderm (outer layer) that will originate the nervous system and the
outer skin, lens of the eye, inner ear, and hair.
▪ The mesoderm (middle layer) that will form the skeletal system and voluntary
muscle
▪ And the endoderm (inner layer) that will form the gut and digestive organs.

 Around the 3rd week, the blastula start the process of gastrulation.
▪ In this process, the cells fold and start becoming different types of tissues.
▪ The early processes that go into forming the nervous system are called
neurulation – induced by the notochord (which will form part of the spinal
cord).

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 The formation of the neural tube occurs between week 3 and 4 in the embryo
development. The neural tube will result in the formation of the brain, the spinal cord
and the meninges.
 Around the week 5, the ectoderm fold around the endoderm and the mesoderm. The
endoderm becomes smaller and the ectoderm becomes larger.

 By the end of the 3rd week, the lateral edges of the ectoderm go up and form the
neural fold. In the middle, a depressed new region is created at the same time, the
neural groove. All this region is called the neural plate.
▪ From a top view, it is important to say that the process starts in the middle
and advance both cranially and caudally. The neural tube starts to fold in the
middle region.
▪ Then, the neural fold fuse together and form the neural tube as a result.
 By the end of week 4, the neural tube is formed (CNS). Some of the cells of the tube
migrate and form the neural crest, this region will form in the future some structures
which work nearby the CNS including the peripheral nervous system, the cranial
nerves, meninges, etc.
 The remaining ectoderm forms the skin.

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NEUROANATOMY

SECTIONS

❖ It is necessary to know the names of the possible sections that we can perform in the brain.
 This is the nomenclature used for the whole body.

MENINGES

❖ Meninges: three membranes covering the brain and the spinal cord.
 Dura mater
▪ Just below the skull bones and vertebral column.
▪ Thick and inflexible.
 Arachnoid
▪ Middle layer.
▪ Avascular and not innervated.
• Right under it is the subarachnoid space, containing cerebrospinal
fluid (acts as a cushion on the brain)
 Pia mater
▪ Below the subarachnoid space.
▪ Very thin and closely adhered to the surface of the brain and the spinal cord.
▪ The only layer following the contours of the brain (gyri)
▪ Highly vascularized to supply the underlaying neural tissue.

❖ Functions: supportive framework for the cranial and cerebral vasculature and protection from
mechanical damage.

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SULCI AND GYRI

❖ Sulci (fissures): depressions in the cerebral cortex.

❖ Gyri: ridge in the surface of the brain.
 The folding of the cerebral cortex that occurs during development of the nervous
system allows us to achieve and economy of size.
 The most important sulci are the longitudinal fissure and the central or Rolando’s
sulcus.
 Right in front and just behind the central sulci, we can find the precentral and
postcentral gyrus.

VIEW OF THE MAIN STRUCTURES

❖ There are different views of the brain: dorsal, ventral, lateral and medial.

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Sagittal view – relevant structures

❖ Hippocampus
 Plays a role in the formation of memory because it is involved in the consolidation of
information, in this way our memories pass from the short-term memory to the long-
term memory.
▪ It is also involved in spatial memory, and it is the first damaged structure in
Alzheimer and types of dementia.

❖ Thalamus
 Egg shaped structure, two gray matter lobes, tucked away (hidden) under the brain
lobes, surrounded by the brain ventricles.
 Gateway to the cortex for the sensory systems, first processing center of sensory
information
 Contains specific nuclei for afferent sensory information connected with all cortical
region: organized according to subdivisions of the thalamus and the projections to the
cortex
 Also controls sleeping function

❖ Hypothalamus
 Quite smaller, almond shaped.
 Underneath the thalamus, in the floor of the third ventricle
 Subdivisions specialized in different functions as the thalamus
 Major control center of the autonomic in motor system
 Involved in hormonal activity and connects the hormonal and nervous systems
 Regulates blood pressure, body temperature and overall homeostasis

❖ Pituitary gland
 Even smaller, bean shaped
 Below the hypothalamus
 The master gland regulates many activities of other endocrine glands.
▪ The hypothalamus decides with hormones the pituitary should release by
sending either hormonal or electrical messages.

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❖ Cerebellum
 Two main structures: cerebellar cortex and subcortical nuclei
 Cerebellar cortex formed by gray and white matters
 Processes inputs from other areas of the brain, spinal cord and sensory receptor and
provides precise timing for coordinated, smooth movements of the skeletal muscles
 Damage may cause dizziness, nausea, and coordination problems

❖ Brain ventricles
 Interconnected cavities filled with cerebrospinal fluid
 Two lateral ventricles, the third ventricle, the cerebral aqueduct and the fourth
ventricle
 Choroid plexuses into de the ventricles produce cerebrospinal fluid (CEF)
 The CEF fills the ventricles and the subarachnoid space
 Cells in the choroid plexuses have a cycle of production and reabsorption of the CEF

Coronal view – relevant structures

❖ Basal ganglia
 Group of neurons bodies (gray substance) – caudate nucleus, putamen, globus
pallidus, subthalamic nucleus and substantia nigra
 Located in the base of the brain, in the middle of ascending and descending axons
 Interconnected with the cortex, the thalamus, and the brainstem
 Cortical-subcortical motor loop
 Play a role on voluntary movements performed in an unconscious way, “putting the
autopilot”
 Monitor motor behaviour

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Ventral view – cranial nerves

❖ The names are related to their function, identified also with a roman number
❖ They can be sensory, motor or both
 Sensory modality composed by sensory afferences
 Motor modality composed by motor efferences

SPINAL CORD AND PNS

❖ The spinal cord is divided into different regions: the cervical, thoracic, lumbar, and sacral
nerves.
 The spinal cord is divided in 30
dermatomes.

❖ This cut of the spinal cord shows the central

butterfly. This region receives this name due to the
shape of the gray matter in the center of the spinal
cord – this structure is formed by neuron bodies.
 Ventral and dorsal roots – are the nerve
roots entering and exiting the spinal cord;
they fuse to form peripheral nerves.
❖ Dorsal ganglion: contains the cell bodies of
peripherical sensory inputs and projects its axons
into the CNS via the dorsal root

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❖ Ventral hon: contains motor neurons that project their axons out the ventral roots to innervate
the peripherical muscles

ARTERIAL BLOOD SUPPLY

LOBES

❖ Frontal lobe
 Structure: superior, middle, inferior and precentral gyri
▪ Three first parallel to longitudinal fissure and precentral gyri in right angle
 Irrigation: anterior and middle cerebral arteries
 Functions
▪ Personality and planification (ideas, reasoning, or emotions)
▪ The region in charge of the language articulation, the Broca’s area, and the
motor cortex (voluntary movements) are included in this section, homunculus
▪ A lesion in this structure can produce personality changes or the Broca’s
Aphasia
❖ Temporal lobe
 Structure: superior, middle, inferior

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▪ Three parallel gyri in horizontal position and the temporal pole

 Irrigation: anterior communicating artery, middle and posterior cerebral arteries
 Functions
▪ Audition, decoding of auditive messages, responsible of spoken language
comprehension, has a role in complex visual tasks as face recognition,
controls some emotions as stress and anger
▪ Contains the primary auditory cortex and Wernicke’s area
❖ Parietal lobe
 Structure: postcentral, supramarginal, angular, inferior parietal and superior partietal
gyri
 Irrigation: anterior and middle cerebral arteries
 Functions
▪ Responsible of the somatosensation and sensorimotor integration.
• It receives the information from the sense organs.
▪ In addition to cognitive functions (mathematical processing, attention, and
working memory)
▪ Contains the somatosensory cortex
❖ Occipital lobe
 Structure: superior, middle, and inferior occipital gyri
 Irrigation: posterior cerebral artery
 Functions
▪ Primary vision cortex, decodes all the visual features, associates these
features with memory and we know what we see
▪ Contains the primary visual areas
▪ Damage can cause partial or complete blindness

❖ Insular lobe
 Structure: short and long gyri
 Irrigation: middle cerebral artery
 Functions
▪ Involved in consciousness and diverse functions linked to emotion or
regulation of homeostasis
▪ Compassion, empathy, taste, perception, motor control, self-awareness, and
cognitive functioning.
▪ Usually involved in psychopathology

❖ Limbic lobe
 Structure: consists of parts of the frontal, temporal and parietal lobes, contains the
hippocampus, hypothalamus, amygdala, fornix, septum, and olfactory bulb
 Irrigation: anterior and middle cerebral
 Functions
▪ Motivation, emotion, learning and memory
▪ It operates by influencing the endocrine system and the autonomic nervous
system.

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NEUROBIOLOGY

CELL MEMBRANES

❖ The atom is defined as the smallest particle of a chemical element that can exist.
 These atoms are present and forming all the material because all the chemical
elements are formed by atoms.
 Bonds
▪ Atoms form bonds to form molecules. There are two types of bonds:
• Covalent bonds: share electrons
• Ionic bonds: transfer electrons

❖ The atoms are formed by 3 types of particles: the protons, with positive charge; the electrons,
with negative charge, and the neutron, with neutral charge.
 The atom nucleus is formed by neutrons and protons while the electrons orbit around
the nucleus.
 The atom stablishes connections between them to form molecules.
▪ The form in which they do it its by sharing or transferring electrons. In this
way, there are two possible types of bonds: the covalent and the ionic bons.

❖ Molecules
 Amphipathic molecules
▪ It means that the molecule possesses a hydrophilic and a hydrophobic part.
The hydrophilic part is polarized, and the hydrophobic part is apolar. With this
type of molecules interact with a water molecule, the hydrophilic part will
enter in contact with the water molecule, not the hydrophobic part.
▪ If we introduce an amphipathic molecule in a water solution, it will adopt this
distribution, with the hydrophilic heads in contact with the water and the
hydrophobic parts in the center forming a kind of ball.
• Electrostatic attractions = attractions between molecules with
opposite charge.

Membranes

❖ The plasma membrane is a structure that surrounds the cell, defining its size and maintaining
the essential differences between the cell content and the external cell environment.
 Formed by a lipid bilayer with proteins and carbohydrates, forming phospholipids.
▪ Lipids + fatty acids.
 The heads of the molecules are hydrophilic lipids, and the tails are fatty acids facing
each other.
▪ The layer thickness 5-10 nm
▪ Identified by Robertson in 1950, defined as a trilaminar structure, sandwich
▪ The bilayer can move by lateral diffusion, rotation of flip-flop.
▪ The cell membrane produces electrical shocks to communicate with other
cellular structures.

❖ Functions:
 Cellular compartmentalization
 Selective permeable barrier
 Solute transport
 Response to external signals – receptors
 Cellular interaction and signalling
 Biosynthesis
 Enzymatic activity

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 Mitochondria – energetic transduction

❖ Composition
 The proportions change a lot depending on the cellular type, but:
▪ Proteins (55-60%)
• The membrane proteins determine the cell function, they are
amphipathic, they can communicate the internal and external cell
environments; and depending on the location, they can be integral
ou peripheral.
▪ Lipids (35-40%)
▪ Carbohydrates (2-10%)
• The carbohydrates can be associated to a protein or to a lipid
inserted in the membrane (glycoproteins, glycolipids). If the
carbohydrates are associated to a transmembrane protein, it will be
a transmembrane glycoprotein.
▪ Very minor component: cholesterol

❖ There are two main structures responsible for the identification of a cell:
 Protein-lipid ratio – membrane type and function
 Glycocalyx – covers the cell membrane (carbohydrates).
▪ Different in each type of cell membrane and acts as a cell identifier.
▪ The proteins associated to the glycocalyx carbohydrates are called
glycoproteins.

❖ Mosaic Fluid Model

 Presented by Singer (1972), explains the structure of the plasma membrane.
 The model has evolved somewhat over time, but it still best explains the structure and
functions of the plasma membrane.
 The fluid mosaic model describes the structure of the plasma membrane as a mosaic
of components – including phospholipids, cholesterol, protein, and carbohydrates –
that gives the membrane a fluid character.

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Membrane types

❖ When the cells are intercommunicated physically in contact there a special kind of structure:
tight junctions. These junctions are formed by proteins which make possible the exchange of
substances between cells avoiding the fugue of any kind of solute or water to the extracellular
space.

❖ Electric synapses
 The neurons that perform the electrical synapses are physically in contact and the
cytoplasm (intracell spaces) are interconnected by tight junctions.

 There are key differences between chemical and electrical synapses.

▪ Chemical synapses depend on the release of neurotransmitter molecules
from synaptic vesicles do pass on their signal, there is an approximately one
millisecond delay between when the axon potential reaches the presynaptic
terminal and when the neurotransmitter leads to opening to postsynaptic ion
channels.
• Additionally, this signalling is unidirectional.

• When an action potential reaches the axon terminal it depolarizes

the membranes and opens voltage-gated Na+ channels.
• Na+ ions enter the cell, further depolarizing the presynaptic
membrane.
• This depolarization causes voltage-gated Ca2+ channels to open.
• Calcium ions entering the cell initiate a signalling cascade that
causes small membrane-bound vesicles, called synaptic vesicles,
containing neurotransmitter molecules to fuse with the presynaptic
membrane.
• Fusion of a vesicle with presynaptic membrane causes the
neurotransmitter to be released into the synaptic cleft – the
extracellular space between the presynaptic and postsynaptic
membranes.
• The neurotransmitter diffuses across the synaptic cleft and binds to
the receptor protein on the postsynaptic membrane.

▪ Signalling in electrical synapses, in contrast, is virtually instantaneous (which

is important for synapses involved in key reflexes), and some electrical
synapses are bidirectional.
• Electrical synapses are also more reliable as they are less likely to be
blocked, and they are important for synchronizing the electrical
activity of a groups of neurons.
o E.g., electrical synapses in the thalamus are thought to
regulate slow-wave sleep, and disruption of these synapses
can cause seizures.

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TRANSPORT

❖ To understand the membrane behaviour, we must know that:

 The gradient is the force which make the charges move.
▪ Is the intensity variation of a property (e.g., temperature, pressure, or
concentration) observed in a distance unit between one point and another
• Vector, direction, and sense in which a phenomenon intensity
increase or decrease
o Concentration
o Electrical
o Electrochemical

▪ K+ ions constitute the internal charge of the cell

▪ Na+ ions constitute the extracellular space charge
▪ The ions concentration is always different on both sides of the membrane.
▪ Charged tend to be balanced – electrostatic forces

❖ Concentration gradient
 A concentration gradient occurs when a solute is more concentrated in one area than
another.
 Concentration is the quantity of a solute in a determined solvent. Particles are in
constant movement and move from areas of higher concentration to areas of lower
concentration to produce an equal distribution in the solution – thermodynamics laws

▪ Over time, solutes always move down their concentration gradient to “try” to
produce an equal concentration throughout the whole solution because the
laws of thermodynamics state that due to the constant movements of atoms
and molecules, substances will move from areas of higher concentration to
lower concentration.

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 Electrical gradient
▪ In this case, we are not referring to the concentration of a substance but to
the charges in two different point. In fact, the electrical gradient is the
asymmetrical distribution of charges from opposite sign between two points.
• In biophysics it is also called potential.

❖ As the membrane is semipermeable: there are any substances that can cross it without
anything else. These movements are performed in favour of the concentration gradient and or
electrochemical without energetic consume. It does not consume energy because this
movement is in favour of the concentration and or electrochemical gradients
 The membrane must be a barrier to everything with electrical charge trying to cross it.
However, all chargeless molecules soluble to the bilayer will pass through it without
energetic consume.

 How do charged or against concentration or big particles cross the cell membrane?
▪ Mediators (proteins): structures that allows the passage of molecules
through the membrane.

Types of transport

❖ The transport through mediators across the membrane can be passive or active. The difference
between them is the energetic consume.
 The passive transport does not require energy, while it is necessary to perform the
active transport of molecules and particles.
▪ As passive transport, we can distinguish between facilitated diffusion and
simple diffusion.
• The simple diffusion does not require any kind of mediators

▪ In the case of passive transport, when mediators act, we can differentiate

between carrier and channel mediators. On the other hand, we have the
active transport, which can be pump and carrier mediated.

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❖ Passive Transport
 It occurs when an ion or molecule crosses the membrane in favour of the
concentration and/or electrochemical gradients, until the balance is reached.
 No energetic expenditure.
 The higher the concentration differences, the higher the flux
 Limit of increasement, saturated transporters – flux maximum

 Simple diffusion
▪ Transport through the lipidic bilayer without proteins participation.
▪ As the membrane is semipermeable, there are many substances that can
cross. How can these substances cross the semipermeable barrier?
• The membrane must be a barrier to everything with electrical charge
trying to cross it. However, all chargeless molecules soluble to the
bilayer will pass through it without energetic consume.
o There are different factors that influence the substances
movements by simple diffusion:
▪ Temperature
▪ Molecular weight
▪ Distance
▪ Cross-sectional area
▪ Gradients
 Facilitated diffusion
▪ There are proteins in the membrane which make possible to transport
substances across the plasma membrane.
• There are two types of proteins that allow passive transport: the
carrier and the channel proteins.
o Only carrier proteins can produce active transport.

▪ The membrane channels are not always open, so how can they be opened?
• There are three main mechanisms:
o Ligand a substance
o Voltage dependent
o Mechanical stimulus

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• Ionophore channels
o Not a protein, in this case we are talking about molecules
soluble in lipids, which are also mediators.
▪ Molecule soluble in lipids
▪ Synthetized by the organism
▪ Transport ions across the membrane
• Two types:
o Channel former
o Carrier channels: small molecules
that bind to a particular ion to
cross the membrane.
❖ Active transport
 Energetic expenditure, against the gradients. It generates electrochemical potentials
▪ Characteristics:
• Saturation
• Competitivity
• Specificity
• Energetic dependent
• Unidirectional
▪ Functions:
• Exchange of cellular material
• pH maintenance and intracellular ionic balance
• Toxic substances removal

 Two types of active transport:

▪ Primary active transport – pump-mediated
• Where is the energy needed in the process coming from?
o The energy derived from the hydrolysis of ATP is used so
that the substance crosses the membrane, modifying the
shape of the transport proteins (pump) of the plasma
membrane.
o The ATP is often referred to as the currency of energy of the
biological systems. It is very important to get to know it
because is the way in which the cells get the energy.
• An example is the Sodium-Potassium pump.
o The sodium-potassium pump is a protein present in all cell
membranes.
▪ Objective: remove sodium from the cell and
introduce potassium into de cytoplasm –

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maintaining a negative charge in the intracellular

space.
• The exchange of ions through the
membrane allows the balance of the
different concentrations both inside and
outside the cell to be maintained.
• The transmembrane protein pumps 3 Na+
ions, expelling it out of the cell, and 2K+
ions into the cell, thus generating a
negative intracellular electrical potential.
• It is produced against the concentration
gradient thanks to the ATP-asa enzyme,
that acts on ATP to obtain the energy
necessary from the nutrients to pass
through the cell membrane and reach the
cytoplasm.
• It is present in the neuron’s membrane.
• Another relevant example is the calcium pump. Important for the
neurotransmitter transport in the neurons. In this case, the calcium
ion must leave the intracellular space – this pump normally
consumes ATP to remove 2Ca+

▪ Secondary active transport – carrier-mediated

• It is the transport of substances that normally do not cross the cell
membrane, such as amino acids and glucose, whose energy required
for transport derives from the concentration of electrochemical
gradient of other substances.
o It can happen both if the transported molecule and the
cotransported ion move in the same direction (symport) or
if they move in the opposite direction (antiport)
• Example: the pump coupled to gradients.
o Na+ tends to go in and glucose tends to go out. But the
glucose has binding sites out of the cell and when the
protein leaves the N+ pass, the glucose is also introduced –
it takes advantage.

 As a function of how the solute is transported, the transporters can be:

▪ Uniport: only transport one molecule.
▪ Coupled Transport: more molecules are transported at the same time (take
advantage of the trip).
• Primary cotransport: both molecules go against the gradients.
• Symport: both molecules go in the same direction
• Antiport: the molecules follow an opposite direction.

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PROTEIN SYNTHESIS

❖ The cell contains various organelles that communicate with each other to generate the
appropriate environment for the cell survival and functioning – there are three main types of
transport that allow them to communicate.
 Gated transport
 Transmembrane transport
 Vesicular transport
▪ Endocytosis – process by which the cell introduces large molecules or
particles by encompassing them in an invagination of the plasma membrane,
forming a vesicle that ends up detaching from the membrane to join the
cytoplasm.
▪ Exocytosis – process by which cells expel macromolecules from their
cytoplasm, transporting them through vesicles to the external environment
and releasing them through the temporary deformation of the plasma
membrane.

❖ Proteins define the cell function and act as receptors for the neurotransmitters in the neuron
membrane.
 How are proteins created?
▪ The cell controls the number and type of proteins in the membrane – cell
autoregulation.
• The lack of neurons autoregulation can cause, for instance, seizures
and epilepsy
▪ Cisterns in the RER (rough endoplasmic reticulum) synthetize proteins.

❖ Protein synthesis
 Most of human cells have a nucleus. The nucleus contains the genome.
▪ Human cells have 23 pairs of chromosomes.
▪ Chromosomes are formed by long strings of DNA, which is packaged around
proteins called histones.
▪ Within the DNA are small sections called genes – these genes contain the
instructions to create proteins.
 When a gene becomes active, an enzyme called DNA polymerase comes to the starting
part of the gene and it moves along the DNA creating a strand of mRNA (messenger
RNA) - transcription
▪ The mRNA is formed by free bases if nucleotides which are present inside the
nucleus.
▪ This process is called mRNA because the nucleotides are added to the mRNA
depending on the free bases present in the DNA which is being transcribed.

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 The RNA is used as a mould for proteins, and it must leave the nucleus and go to the
cytoplasm. It goes to the ribosomes, which are the protein factories of the cell.
▪ The ribosome reads the code of nucleotides and creates a chain of amino
acids – translation process.
▪ Each three nucleotides correspond to an amino acid (there are 20 types, in
total).
▪ Once the chain in completed, the amino acids fold in a 3D shape – the
protein.
 Once the ribosome creates the new protein, the chain goes to the endoplasmic
reticulum.
▪ Another protein, called SRP comes to the ribosome when the protein is being
synthetized. It joints to the sequence of nascent polypeptide and guides the
ribosome to a SRP receptor in the membrane of the RER.
▪ Once the SRP is attached to its corresponding receptor in the RER, the new
protein interacts with the protein translocator which is included also in the
membrane and finally the protein is included in the membrane through a
plug.
▪ Once the protein crosses the reticulum membrane it will be expelled outside.

 Once the proteins are created and included into the endoplasmic reticulum, there is
an intermedium step.
▪ From rough endoplasmic reticulum to Golgi apparatus (in a vesicle).
▪ The Golgi apparatus is a major collector and sender station of proteins.
▪ When necessary, the proteins are packaged into a vesicle and expelled out.

 The protein must cross the Golgi apparatus.

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▪ The Golgi apparatus is directly in contact with the cell membrane and with
other organelles and can produce the vesicles to transport the proteins to
their final destinations.
▪ There are two pathways.
• Constitutive if the vesicles membrane content is included in the cell
membrane (membrane lipids and proteins).
• Or regulated by hormones or neurotransmitters.
o Joined to the cell membrane, originate the secretion of
proteins to the extracellular space, this is the regulated
pathway because it depends on the joint of other
substances to the membrane.
▪ This is how proteins get to the cell membrane of to
the extracellular space.

NERVOYS SYSTEM CELLS

❖ The nervous system is mainly composed by two types of cells: the neurons and the glia.
 Neurons
▪ Excitable cell able to receive a stimulus, transmit the nervous impulse and
send it to another neuron.
• Components
o Soma: controls all the system, has the nucleus
o Neurites (dendrites and axons): projections of the cell body
▪ Dendrites: thicker, receive connections as the
soma
▪ Axons: begin in the amyelinic axon hillock
o Dendritic spines: profusion from a dendrite which switch
on/off synapses (contact with axons and can retract to
avoid the contact)
o Telodendron: set of terminal branches of the axons
o Microtubules: allow the transport along the axon
o Axon hillock: where the action potential is fired, amyelinic.
▪ Types of neurons
• Depending on their structure, the neurons can be classified as
o Unipolar
▪ A single projection which is divided in two or more
branches.

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▪ Mostly sensorial and in the PNS.

o Bipolar
▪ Only two projections which start from the soma,
one dendrite, one axon.
▪ Elongated shape.
▪ Are rare, specialize in reception and transmission
of signals from the sense organs
o Multipolar
▪ More frequent (99%)
▪ Three or more dendrites and an axon starting from
the soma.
▪ Interneurons and motor neurons.
▪ Implicated in muscles system modulation, learning,
behaviour and memory.
 Glia Cells
▪ The Glia cells were analysed in detail by Ortega with gold-sublimate method.
▪ Astrocyte
• Responsible for feeding and protecting the neurons.
o Cover the blood vessels to avoid contact between neurons
and blood vessels.
o Blood-brain barrier
o Like neurons, with sucking feet.
▪ Schwan cells and oligodendrocytes
• Insulate the axons to facilitate (without power low) and accelerate
(saltatory transmission) the nervous impulse transmission.
o Form the myelin.
o Same type of cell in the PNS and de CNS.
o Growth with neurons in the embryony development and
cover the axons.
o A single cell can cover multiple neurons.
▪ The space without myelin are the Ranvier nodes
(Na+ corridor)
▪ Microglia
• Responsible for the protection of neurons and cleaning the
extracellular environment.
o In normal conditions, they maintain the cell environment
and clean in case of lesion
▪ Ependymal cells
• Creation and circulation of cerebrospinal fluid into the ventricles.
• Current research on potential power to create new neurons in
adults.

❖ The neuron must inform the nucleus about its necessities.

 The signals get to the telodendrion and if more or less “power” is needed, a signal is
sent to the nucleus of the neuron to synthetize or remove receptor proteins,
neurotransmitters or cellular extension.
 To be able to control every aspect of the body functioning, the neurons should know
which neurotransmitters (and receptor proteins) and in which proportion they must
synthetize.
▪ These factors depend in their necessities and on how they work. When the
activity is far from the soma, there are back signals that get to the nucleus.

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SYNAPSES

❖ Synapses are the first and the last step in neural communication.
1. The action potential reaches the axon terminal
2. CA+ voltage dependent channels open
3. Neurotransmitters are released to the synaptic cleft.
4. Joint of neurotransmitters to postsynaptic receptors.
5. NA+ channels open

❖ There are three possible classifications of synapses, depending on the:

 Causes
▪ Chemical
• Involves release of chemical messengers (neurotransmitters).
• Neurotransmitters carry information from the presynaptic (sending
neuron) to the postsynaptic (receiving cell).
o More complex, ore frequent, slower but easily controlled.
▪ Electric
• Consists in the direct physical connection between the presynaptic
neuron and the postsynaptic neuron.
o This connection takes the form of a channel called gap
junction, which allows current (ions flow) directly from one
cell into another.
▪ Faster but uncontrollable
▪ Mixed

 Regions in contact
▪ Axo-axonic
▪ Axo-dendritic
▪ Axo-somatic
▪ Axon-muscle
• Placa motora: sinapse entre neurónios e músculos.
• E.g., terminais que acabam nos músculos e libertam acetilcolina que
contrai os músculos

 A neuron can receive excitatory of inhibitory potentials.

 Effect of the neurotransmitters (excitatory or inhibitory)
▪ The bind of a neurotransmitter to a receptor can produce changes in the
membrane potential of the receiving cell.
• If this change makes the cell more likely to fire an action potential,
then it is an excitatory postsynaptic potential, or EPSP.
• If it makes the cell less likely to fire an action potential, it is an
inhibitory postsynaptic potential, or IPSP

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▪ Excitatory and inhibitory potentials have the opposite effect.

• Hence when it must be decided if the action potential is fired or not,
the excitatory and the inhibitory potentials are fighting.
• However, they are not alone. There are two of more factors that can
influence the intensity of the neuron depolarization – the integration
of all the action potentials which are reaching the neuron at the
same time or in a concrete space.
o Temporal summation: sum of the EPSP and IPSP generated
simultaneously in the dendrite.
o Spatial summation: summation of EPSP and IPSP generated
in the same synapsis with a latency of 1-15ms between
them.

Homeostatic Plasticity

❖ The homeostatic plasticity: mechanism by which neurons regulate the synaptic strength by
controlling the quantity of postsynaptic receptors.
 More receptors = more neurotransmitters arriving to the neuron and a stronger
synaptic power and more probability of depolarizing the neuron and transmitting the
nervous impulse.
▪ Example: AMPA receptor homeostasis
• Receptor for glutamate
• Mediates the fast synaptic transmission in the nervous system.
• Most abundant in the nervous system
o AMPARs are scaled in response to chronic changes neuronal
activity
a) In conditions of persistent high activity, high
levels of Arc are available to facilitate the
endocytosis of AMPARs, with consequent
downregulation of receptors in the membrane
b) At levels of normal neuronal activity, during
which Arc appears, and thus a constant level of
surface receptors is homeostatically maintained
c) In conditions of persistent low activity, during
which Arc expression is dramatically reduced,
Arc-dependent endocytosis is minimized. The
number of receptors increase.

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ACTION POTENTIAL

❖ Whitin the axon, the molecules can move in both directions, from the soma to the telodendrion
and vice-versa. This transport is essential for all functions performed in the axon terminals.
 The microtubules in the interior of the axons are the way in which all the substances
which are transported cross the neuron.
▪ The microtubules also play an important role in the axonal growth.
• Axon can branch out and create new axon terminals.
• In the extreme of the neuron there are always synaptic structures
which are in touch with other neurons, muscles, and glandular cells.

 This transport can occur in two directions: anterograde and retrograde.

▪ Anterograde
• From the soma to the telodendrion
• We can distinguish between
o Fast transport
▪ The kinesin is the protein in charge of the fast
transport of substances in the anterograde
transport.
▪ This protein associates with microtubules and
consumes ATP. On one hand, it binds to the
microtubules and on the other hand, it binds to the
vesicle that must be transported.
• The bind to the microtubules suffers cyclic
changes and this moves the vesicle from

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one extreme of the microtubule to the

other.
o Slow transport
▪ Retrograde
• It can also be
o Fast transport
▪ The fast transport depends on the protein dynactin
that is also able to transport vesicles.
▪ In this case, the dynactin cannot transport the
vesicles by itself, it needs to be associated with
proteins that are attached to the microtubules.
o Slow transport

❖ Galvani was a pioneer in demonstrating that the transmission of the signals in the nervous
system was relate to electrical activity.
❖ The reason why the neurosciences emerge later than the other sciences was due to the
necessity electrophysiological techniques to analyse the neuronal responses.
 1950 it was discovered that the ions of sodium flux are the responsible for the
transmission of the nervous impulse.
 The first register of the electrical activity in an axon was taken in a squid.
▪ The resting potential is at -70mV.
▪ It becomes positive until 50mV and then falls again bellow zero to finally
reach the resting potential again.

❖ Resting potential
 Defined as (intracellular potential – extracellular potential)
 In neurons around -70mV
 Non-zero membrane potential
 Depends on resting channels
 In the resting state: Na+ and K+ passive channels are open, ion gated closed and
Na+/K+ pump working
▪ Na+/K+ pump – moves out 3Na+ and introduces 2K+
▪ The global balance is a lost of + charges into the neuron

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❖ Phases in the Action Potential transmission process

 Resting state: gated Na+ and K+ channels closed.

▪ Resting potential maintained by ungated channels /Na/K pump and passive
channels).
 Depolarization: membrane permeable to Na+, the Na+ goes inside the cell.
▪ If the depolarization reaches a threshold, the action potential is triggered.
 Rising phase: depolarization opens Na+ channels and potassium channels are still
closed.
▪ Positive intracellular space
 Falling phase: sodium channels inactivated 10ms later, refractory period.
▪ No more Na+ going inside, K+ channels open and K+ outflow.
▪ Negative intracellular space again
 Undershoot: Na+ channels continue closed but some K+ still open
▪ When closed, K+ channels reach their refractory period
 After a brief time, after the refractory periods, the channels can be opened again
❖ The channels are the absolute responsible for the transmission of the action potential.
 The Na+ channels voltage dependent are the main responsible of the signal
propagation.
 The K+ channels re-establish the charges balance.

 Channels behaviour
▪ Three phases: resting, open and closed.
▪ The channels kinetic depends on their molecular structure and they respond
as an all-nothing system.

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❖ Once the neuron becomes depolarized and the action potential threshold is reached, the action
potential must be propagated along the axon.
 To this end, the axons are covered by myelin - which is formed by Swan cells and
oligodendrocytes. This formation is called Myelin sheaths (shizzs)
❖ When the action potential is shooted, the charged in both sides of the membrane change, the
interior becomes positive and the exterior negative.
 The impulse travels along the axon and the anterior parts are repolarized. When the
depolarization reaches the threshold, the voltage dependent channels open and the
Na+ goes inside the membrane. After that, the K+ channels open and the inactivation
gate of the Na+ channel is closed. The exit of K+ ion make the charge going below -
70mV. Finally, the Na+ channels become open newly.
❖ The reason why the action potential cannot travel backward is because the previous section of
the axon membrane is in ARP and the action potential can only be propagated forwards.

❖ Myelinization
 The charges expand along the axon and myelinization prevents ions lost by crossing
the plasma membrane.
 Charges expand without stop until an myelinic region (Ranvier node)
 Na+ and K+ channels available in the Ranvier node

NEUROTRANSMITTERS

❖ Chemical messengers:
 Gamma-aminobutric acyd (GABA)
▪ Main inhibitory neurotransmitter in all the CNS.
▪ Reduce the neuronal excitability
 Glycine
▪ Main inhibitory neurotransmitter in the spinal cord and brainstem.
▪ Alterations cause spastic paralysis due to uninhibited muscle contraction
 Glutamate
▪ Main excitatory neurotransmitter in the CNS
 Acetylcholine
▪ Excitatory and inhibitory functions in the union between neuron and muscle
 Dopamine
▪ Motivational prominence and motor functions

CIRCUITS AND NEURONS ORGANIZATION

❖ Nervous system nucleus

 Sets of neurons which develop a common function and are in a concrete anatomical
region.
▪ For instance, there are regions directly implicated in the transmission of
auditive information
 The nucleus are interconnected and there are two types of neurons in the nucleus:
▪ Type I
• Long axon neurons
• Send signals from a nucleus to another.

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• The set of neuron axons are organized in fibre bundles which go

from a nucleus to another.
o These bundles constitute the white matter (myelin) and the
somas in the nucleus are the gray matter (a myelinic region)
▪ Type II
• Short axons
• Don’t leave the space where they work
• Regulate the nucleus functions

❖ Brain vs. spinal cord

 In the brain, the gray matter is located outwards and the white matter inwards.
▪ In the brain, connections are mainly divided in associative and commissures.
• Associative tracts connect different brain nucleus
• Commissures connect both hemispheres
• Projection fibres connect nucleus outside and inside the brain.
 In the spinal cord, the gray matter is located inwards and the white matter outwards.

❖ Example
 Reflexes: the simplest mechanism in
the body.
▪ Patellar reflex
▪ Tendon struck – reflex
mechanism activated

 Hit the tendon, information received

by a sensory neuron travel to the
spinal cord.
 In the spinal cord, the sensory neuron
contacts two neurons: one excitatory
and one inhibitory (interneuron)
▪ Inhibit the flexor motor
neuron of the biceps and
activate the extensor motor
neuron to the quadriceps.
 Not going to the brain, reacting fast

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ASCENDING PATHWAYS: TOUCH, SMELL AND TASTE

SOMATOSENSORY SYSTEM OVERVIEW

❖ From an anatomical point of view, the nervous system is divided between central and
peripheral nervous systems.
 The CNS is composed by the encephalon and the spinal cord.
▪ The encephalon is divided in the brain, cerebellum, and brainstem.
 The PNS is composed by the spinal nerves.
❖ From a functional point of view, the peripheral nervous system is divided in autonomic and
somatic nervous systems.
 And the autonomic can be divided in sympathetic and parasympathetic.

❖ The spinal cord is there the spinal nerves start.

 There are a total of 30 spinal nerves starting in 30 spinal segments (so, we can divide
the body in 30 dermatomes, where each of the dermatomes is innervated by a spinal
nerve).
 The dorsal horns carry sensory information coming from sensory neurons. The sensory
information gets to the spinal ganglia and ascent to the somatosensory cortex.
 In the ventral horns, we can find the motoneurons that innervate all the body
muscles.
▪ The morphology of the ventral horns changes as a function of the location in
the spinal cord. For instance, at the level of C5 and L1, the ventral horns are
bigger because here occurs the innervation of the arms and legs muscles
which are considered as big muscular groups.

▪ There are cases in which the information doesn’t rise to the cortex.
• In these cases, we would be talking about reflexes arc. In reflex
movements, normally, a sensory and a motor neuron stablish
connections in the spinal cord, and sometimes a motor neuron is
also implicated. The interneurons act as an integration system.
• The remaining signals rise to the cortex, concretely to the primary
sensory and motor areas.

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❖ The thalamus in the gateway to the cortex.

 From a functional point of view, it is formed by different nuclei.
▪ Almost all the sensory information coming from the sense organs must cross
this gateway before rising to the cortex – except for the smell sense.
• The information coming from the smell sense connects somehow
with the rest of the brain and enters the cortex, but as a later step.
The smell information enters as first step to the hippocampus
(olfactory memory) and the amygdala (fear).
o This is the reason why some smells evoke emotions.

TOUCH AND SOMATIC SENSATION

❖ Touch sensations vs. somatic sensations

 Differentiate between feeling something in the skin (touch, pressure) and processing
these sensations (somatic) in the brain.
❖ There is a variety of receptors sensitive to physical deformation, physical phenomenon, and
chemical substances.
 There are 4 types of receptors
▪ Mechanoreceptors
▪ Pain receptors
▪ Thermoreceptors
▪ Propioceptors

Skin

❖ The skin is a layer that protects us and allows us to interact with the surrounding environment.
 Divided in three layers:
▪ Epidermis (epithelial tissue, not vascularized)
▪ Dermis (conjunctive tissue, vascularized)
▪ Hypodermis (adipose tissue)
 Fat layer varies (adipose tissue) as a function of the body part and also between
women and men.
▪ Men face > woman face, but it is the opposite in the rest of the body (women
skin is softer)

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Mechanoreceptors

❖ Mechanoreceptors and Free Nervous Endings

 Free nervous endings: pain, itchiness, and temperature.
▪ Without associated receptors, associated to other elements that help them in
the reception process.
▪ Epidermis and in hairy and glabrous skin
 Pacinian corpuscle: pressure and vibration.
▪ Very big and surrounded by a conjunctive tissue layer.
▪ In both dermis and hypodermis, both hairy and glabrous skin.
 Ruffini’s ending (lung shape): pressure and touch.
▪ Smaller than Pacinian.
▪ Between dermis and hypodermis, both hairy and glabrous.
 Merkel’s receptor: touch.
▪ Associated to non-flattened epithelial cells in the epidermis, mostly hair skin.
 Meissner corpuscle: light touch.
▪ Under the epidermis and complex structure, mostly glabrous skin.
 Hairy skin receptor: joined to hairs.
▪ Detects the movements.
▪ Only in hairy skin.

 There is another type of mechanoreceptors that appear in animals – vibrissa

▪ These are long, stiff and thick hairs growing around the mouth or elsewhere
on the face of many mammals, known as whiskers.
▪ Used to detect movement and very organized somatotopic representation.

❖ Receptive field and adaptation

 Receptive field: territory in which the receptors can detect the signals.
 Adaptation: concerning the firing rate of the cell.
▪ Fast adaptation cells: fire and stop after a brief time after the pressure is
detected (outer layer cushion) and continue firing once the pressure is
released and slow adaptation cells fire when pressure is put on them and
then continue firing but in a slower manner.

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 Pacini example (fast adaptation)

▪ The capsule that wraps the receptor cushions the pressure on it causing the
fast adaptation and the cell continues firing if the pressure is removed. If the
capsule is removed, the adaptation would be very slow (nothing to cushion)

Pain receptors

❖ Pain is to feel or perceive unpleasant sensations coming from any region of the body.
❖ Nociception is the process that evoke this pain sensations.
 The term comes from the latin nocere.
▪ It is specially controlled by the brain because this perception is essential to
survive – we must know if any stimuli is hurting us.
 Nociceptors
▪ Are captured by free nervous endings.
▪ Activated by stimuli able to produce a tissular damage: intense mechanical
deformation, extreme temperature, lack of oxygen and chemical agents.
▪ High threshold to fire.
▪ Poor adaptation (no capsules in free nervous endings)
▪ Hyperalgesia (hypersensitivity to pain)

❖ Most of these receptors are polymodal, which means that are sensitive to more than one kind
of stimulus.
 Can be mechanical, thermal, chemical
 There are few unimodal receptors, specific for mechanical or thermal, or chemical.
▪ E.g.,
• Bee sting: ligand activated channels-poison
• Fire: sensitive to temperature
• Muscles hurt when we can’t run anymore.

❖ Pain regulation
 The pain sensation can be regulated by different vias.
▪ Afferent regulation
• No nociceptive fibres inhibit by means of interneurons to second
order neurons (2nd neuron in the pathway)
▪ Efferent-descendent regulation
• Different regions of the brain, pain bear mechanism.
• Inhibition to the spinal neurons
 Endogenous opiates

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▪ Endorphins are by the amygdala and the brain, and cause the inhibition of the
pain sense in different ways (hyperpolarization, neurotransmitter
reduction,…)
• These natural chemicals act as powerful pain relievers and stimulate
pleasure centres creating satisfying situations that help eliminate
discomfort – some people like feeling pain, if fact they inhibit pain
and feel pleasure.

Thermoreceptors

❖ Characteristics
 Free nervous endings
 Ionic channels regulated by temperature (Na+ and Ca2+)
 Very sensitive to thermal changes (0.01ºC)
 Specific for cool and hot, and mixed
 Specific for temperatures (6 types)
 Areas insensitive to temperature depending on the receptors

Proprioceptors

❖ Proprioception: knowledge about the position and movement of the body in the space. Even
closing our eyes, we are conscious of the position of our bodies (e.g., hands up or down)
 There are three types
▪ Muscle spindle
• Extrafusal (muscle contraction) and intrafusal (extension) fibres
• Inside the muscle (parallel position)
• Inform about the degree of extension
▪ Golgi tendon organ
• In tendons
• Inform about too intense muscles contractions
▪ Articular receptor
• Informs about the position of the articulations (angle, speed and
direction)
• In articular capsules and ligaments
• Combined with the others

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Types of afferent axons

Ascending pathways

❖ All the information coming from these receptors must rise to the cortex.

❖ Posterior column – medial lemniscus pathway

 Fine touch, vibration, pressure, two-
point discrimination and proprioception
from the skin and joints (touch and
proprioception)
 Big axons
 Pathway: information gets to the neuron
soma in the dorsal root ganglion, the
axon is divided, one branch for the
ventral via (myotatic reflex) and the
other axon travels up the spine in the
posterior column.
▪ In the medulla oblongata,
occurs a decussation (cross
midline) and the synapses with

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the second neuron.

▪ The second neuron ascends to the thalamus. In the thalamus, occurs the
synapses with the third neuron that reaches the cortex.

❖ Spinothalamic tract pathway

 Nociception and temperature
 Small axons
 Pathway: information gets to the neuron soma in the dorsal root ganglion, pass by the
dorsal horn, where the synapses with the second neuron occurs.
▪ The second neurons cross the midline (decussation), and ascends towards the
spinothalamic fascicle, cross the medulla oblongata and reach the thalamus.
▪ In the thalamus, the synapses with the third neuron occurs. This third neuron
carries the information to the cortex.

❖ Trigeminal pathway
 Face sensitivity (trigeminal nerve)
 Two vias analogous to spinal pathways (one for touch and proprioception and other
for nociception and temperature)

 Touch and proprioception

▪ Synapses in the ipsilateral trigeminal
nuclei located in the pons, the second
neuron decusses and ascends
towards the thalamus where the
synapses with the third neuron
occurs. Finally, this third neuron
travels up to the cortex.
 Nociception and temperature
▪ Synapses in the medulla oblongata,
concretely in the trigeminal spinal
nuclei. The second neuron decussed
and reach the thalamus.
▪ The synapses with the third neuron
occurs, and the information finally
gets to the cortex.

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CHEMICAL SENSES

❖ Chemical senses
 Chemical receptors, the most primitive
 Primitive bacteria had receptors for aquatic chemical substances
 Adaptation of chemical receptors to air
 Currently, almost all cells have chemical receptors to communicate with other cells
and with the external environment

Chemical receptors

❖ Nervous endings in the skin: nociception for irritants

❖ Digestive organ: ingested substances detection and pH detection.
❖ Blood vessels receptors: pH detection, O2 and CO2 levels.
❖ Muscles receptors: lactic acid receptors

❖ There are different types of chemical receptors

 Olfactory receptors: smells
 Taste receptors: flavors.

SMELL

❖ There are different types of smellers

 Macrosmatic: very big olfactory bulb (e.g., mouse, dog)
 Microsmatic: olfactory bulbs small compared to the rest of the body (e.g., human)
 Anosmatic: no olfaction (e.g., dolphin)

Olfaction organ

❖ The olfactory epithelium is placed in the top part of the nostrils and here is where the
substances receptors are located.
 The cells that can be found in the olfaction organ are:
▪ First neuron (bipolar)
• Small receptor cell
• The smell receptors are located in the cilia. The information goes to
the axon, cross the ethmoid bone (there are holes in the bone). The
grouping of all these axons forms the olfactory tract.

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▪ Sustentacular cells: supports the epithelium.

▪ Basal cells: acts as mother cells.
• Continuous renewal of smell receptors neurons in a cycle between 4-
8 weeks. When a neuron dies, a basal cell is divided in 2, a basal cell
and a new smell neuron. The new neurons sends its axon to the
correct location in the olfactory bulb by a mechanism (which is
unknown and known at the same time)
▪ Bowman glands: secret mucus.
• Possesses molecules able to retain odorants and make them arrive
to the cilia and enzymes that degrade estrange substances.

Types of neurons

❖ Ramon Molinere presented a classification of the neurons as a function of their structure

 Bipolar: only two projections which start from the soma, one dendrite, one axon.
▪ Elongated shape. Are rare, specialize in reception and transmission of signals
from the sense organs.

Signal transduction

❖ The olfactory receptor neurons are bipolar and, in their membrane, they have odor receptors
joined to protein G.
 In the case, it is called Gold, because it is specific for the olfaction sense.
 The alfa subunit type stimulates the adenylate cyclase that increase the concentration
of AMPc adenosin monophosphate that opens ionic channels or activate enzymes. In
this case, the AMPc open the ionic channels for NA and CA, the membrane becomes
depolarized and the action potential starts.
 Unlike most of the body cells, here we can find more concentration of CL in the
internal cell environment. The CA entering opens the CI channels that goes out in favor
of the concentration gradient.
▪ In this way, the positive intracellular charge fires the action potential.

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❖ Receptors adaptation
 Fast adaptation to odors
▪ Due to odor diffusion
▪ The mucus possesses enzymes to remove the odorants
▪ AMPc activates signal ending routes
▪ Channels saturation
• Adaptation time: 1 minute

❖ Receptors specificity
 Odor receptors
▪ Largest gene family in mammals
▪ 1200 rats vs. 350 humans
▪ Dispersed throughout the
genome

 How many smells can we identify?

Human – 10.000 smells
▪ Each cell expresses only
one or a few related
receptors (specificity)
▪ Respond preferably to a
molecule but can respond
to more than one (even
more specificity)
▪ Each smell is in fact a
combination of odorants
▪ The different receptors
are mixed in the
epithelium but keep
certain order.

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❖ From the epithelium to the olfactory bulb

 The first neuron send the information to the olfactory bulb, concretely to the
glomerulus. The receptors neurons carrying the same type of information of
responding to the same type of receptor send the axon to the same glomerulus.
▪ Glomerulus
• Connections establishment
• Convergence of 250.000 axons
• Projections dendrites (mitral cells)
• From the glomerulus to superior centers

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❖ From the olfactory bulb to superior centres

 Olfactory bulb = olfactory primary cortex
 Olfactory secondary cortex = rest of centres in the rest of the brain (anterior
olfactory nucleus, rostro-medial olfactory cortex and lateral olfactory cortex)

 Some regions related to hippocampus and amygdala = smells evoke memories

and emotions

 The smell information foes to the thalamus only secondarily (indirectly and in
a minor portion = only conscious part)
 All the brain regions are related in some way with the sense of smell.

TASTE

❖ There are 5 basis tastes/flavours: sweetness, saltiness, bitterness, sourness and

umami.
 There is 1 more that sometimes is considered: fattiness.
▪ Humans have a preference for the sweet taste due to the breastmilk
that we have when we are babies, and in general the evolution has
always made us flee from the bitter taste because most of the plant’s
poisons are bitter.
▪ However, the taste can be educated and we get used to bitter, for
instance beer or coffee.

The taste organ

❖ Formed by:
 Tongue
▪ The tongue has taste buds, 4 types:
• Fusiform
• Fungiform
• Foliate
• Circumvallate

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▪ In the lateral portion of the taste buds, we can find the taste receptors
(gustative cells)
▪ The whole tongue is able to detect all the tastes but there are regions
which are more specialized in specific tastes. Theoretically, each bud
respond to a single taste but if the taste is very concentrated it can
also respond to this taste. So, there is kind an non-specificity with
taste receptors
 Palate
 Epiglottis
 Pharynx

Transduction mechanism

❖ Salty and sour depend on ionic channels

 Salty: Na+ channels, Na+ goes inside and produces the membrane
depolarization, which opens the CA2+ channels and the calcium produce the
neurotransmitter release to the afferent taste axons
▪ Not neurons but neurotransmitter release
 Sour: question of pH, which is concentration of hydrogen ion
▪ H+ enters the cell by proton channels, depolarization, protons inhibit
the exit of K+ (more depolarization).
▪ Open voltage-dependent Na+ and Ca2+ channels.
▪ Two mechanisms
▪ Neurotransmitter release

❖ Sweet, umami and bitter: depend on Gprotein-couples receptors

 The taste molecule joint to the receptor protein activates the Gustducin.
 Gustducin activates a membrane protein, the phospholipase C

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 This protein is divided in two subunits, another membrane protein that

remains in the membrane and in IP3 (inositol-trifosfate) = second messenger.
 IP3 goes into the endoplasmic reticulum and orders the Ca2+ release that
provokes the neurotransmitter exit.

Central Pathways

❖ There are 3 cranial nerves implicated in this process.

 Neuron 1: bipolar neuron – gustatory nucleus of medulla oblongata
 Neuron 2: decuse and rise to the thalamus
 Neuron 3: finally getting to the cortex

Theory of neurons populations decoding

❖ The perception of taste is more complex that it seems to be:

 Different signals are integrated creating a complex palatar pattern.

 Each bud responds to different tastes in high concentration (90% two tastes)
but certain preference
 Each axon carries information from different buds and each cell in the nucleus
receives information from different afferent axons
▪ Taste is influenced by smell, touch and even vision.
▪ Information is shared to create a complex perception – at cortical
level.

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