Anfis sistem saraf

David R
 Nervous System

• 2 types of cells in the nervous system:

– Neurons.
– Supporting cells.
• Nervous system is divided into:
– Central nervous system (CNS):
• Brain.
• Spinal cord.
– Peripheral nervous system (PNS):
• Cranial nerves.
• Spinal nerves.
 Neurons

• Basic structural and functional units of the nervous

system.
– Cannot divide by mitosis.
• Respond to physical and chemical stimuli.
• Produce and conduct electrochemical impulses.
• Release chemical regulators.
• Nerve:
– Bundle of axons located outside CNS.
• Most composed of both motor and sensory fibers.
 Neurons (continued)

• Cell body (perikaryon):

– “Nutrition center.”
– Cell bodies within CNS clustered into nuclei, and in PNS in ganglia.
• Dendrites:
– Provide receptive area.
– Transmit electrical impulses to cell body.
• Axon:
– Conducts impulses away from cell body.
– Axoplasmic flow:
• Proteins and other molecules are transported by rhythmic contractions to
nerve endings.
– Axonal transport:
• Employs microtubules for transport.
• May occur in orthograde or retrograde direction.
Neurons (continued)
 Functional Classification of Neurons

• Based upon direction

impulses conducted.
• Sensory or afferent:
– Conduct impulses from
sensory receptors into
CNS.
• Motor or efferent:
– Conduct impulses out of
CNS to effector organs.
• Association or
interneurons:
– Located entirely within the
CNS.
– Serve an integrative
function.
 Structural Classification of Neurons

• Based on the # of
processes that extend
from cell body.
– Pseudounipolar:
• Short single process that
branches like a T.
– Sensory neurons.
– Bipolar neurons:
• Have 2 processes.
– Retina of the eye.
– Multipolar:
• Have several dendrites
and 1 axon.
– Motor neuron.
 PNS Supporting Cells

• Schwaan cells:
– Successive wrapping of the cell membrane.
– Outer surface encased in glycoprotein basement
membrane.
– Provide insulation.
• Nodes of Ranvier:
– Unmyelinated areas between adjacent Schwaan cells
that produce nerve impulses.
• Satellite cells:
– Support neuron cell bodies within ganglia.
 CNS Supporting Cells

• Oligodendrocytes:
– Process occurs mostly postnatally.
– Each has extensions that form myelin sheaths around several
axons.
• Insulation.
 Nerve Regeneration

• Schwann cells:
– Act as phagocytes, as the distal neuronal
portion degenerates.
– Surrounded by basement membrane, form
regeneration tube:
• Serve as guide for axon.
• Send out chemicals that attract the growing axon.
• Axon tip connected to cell body begins to grow
towards destination.
 Nerve Regeneration (continued)

• CNS has limited ability

to regenerate:
– Absence of continuous
basement membrane.
– Oligodendrocytes
molecules inhibit
neuronal growth.
 Synapse

• Functional connection between a neuron and

another neuron or effector cell.
• Transmission in one direction only.
• Axon of first (presynaptic) to second (postsynaptic)
neuron.
• Synaptic transmission is through a chemical gated
channel.
• Presynaptic terminal (bouton) releases a
neurotransmitter (NT).
 Electrical Synapse

• Impulses can be
regenerated without
interruption in adjacent
cells.
• Gap junctions:
– Adjacent cells electrically
coupled through a channel.
– Each gap junction is
composed of 12 connexin
proteins.
• Examples:
– Smooth and cardiac
muscles, brain, and glial
cells.
 Chemical Synapse

• Terminal bouton is
separated from
postsynaptic cell by
synaptic cleft.
• NTs are released from
synaptic vesicles.
• Vesicles fuse with axon
membrane and NT
released by exocytosis.
• Amount of NTs released
depends upon frequency
of AP.
 Synaptic Transmission

• NT release is rapid because many vesicles form

fusion-complexes at “docking site.”
• AP travels down axon to bouton.
• VG Ca2+ channels open.
– Ca2+ enters bouton down concentration gradient.
– Inward diffusion triggers rapid fusion of synaptic vesicles
and release of NTs.
• Ca2+ activates calmodulin, which activates protein
kinase.
• Protein kinase phosphorylates synapsins.
– Synapsins aid in the fusion of synaptic vesicles.
 Synaptic Transmission (continued)

• NTs are released and diffuse across synaptic cleft.

• NT (ligand) binds to specific receptor proteins in
postsynaptic cell membrane.
• Chemically-regulated gated ion channels open.
– EPSP: depolarization.
– IPSP: hyperpolarization.
• Neurotransmitter inactivated to end transmission.
 Chemical Synapses

• EPSP (excitatory
postsynaptic
potential):
– Depolarization.
• IPSP (inhibitory
postsynaptic
potential):
– Hyperpolarization
 Acetylcholine (ACh) as NT

• ACh is both an excitatory and inhibitory NT,

depending on organ involved.
– Causes the opening of chemical gated ion channels.
• Nicotinic ACh receptors:
– Found in autonomic ganglia and skeletal muscle fibers.
• Muscarinic ACh receptors:
– Found in the plasma membrane of smooth and cardiac
muscle cells, and in cells of particular glands.
 Monoamines as NT

• Monoamine NTs:
– Epinephrine.
– Norepinephrine.
– Serotonin.
– Dopamine.
• Released by exocytosis from presynaptic
vesicles.
• Diffuse across the synaptic cleft.
• Interact with specific receptors in
postsynaptic membrane.
 Inhibition of Monoamines
as NT

• Reuptake of
monoamines into
presynaptic membrane.
– Enzymatic degradation of
monoamines in
presynaptic membrane
by MAO.
• Enzymatic degradation
of catecholamines in
postsynaptic membrane
by COMT.
 Serotonin as NT

• NT (derived from L-tryptophan) for neurons with

cell bodies in raphe nuclei.
• Regulation of mood, behavior, appetite, and
cerebral circulation.
• SSRIs (serotonin-specific reuptake inhibitors):
– Inhibit reuptake and destruction of serotonin,
prolonging the action of NT.
– Used as an antidepressant.
• Reduces appetite, treatment for anxiety, treatment for
migraine headaches.
 Dopamine an NT

• NT for neurons with cell bodies in midbrain.

• Axons project into:
– Nigrostriatal dopamine system:
• Nuerons in substantia nigra send fibers to corpus straitum.
• Initiation of skeletal muscle movement.
• Parkinson’s disease: degeneration of neurons in substantia
nigra.
– Mesolimbic dopamine system:
• Neurons originate in midbrain, send axons to limbic system.
• Involved in behavior and reward.
• Addictive drugs:
– Promote activity in nucleus accumbens.
 Norepinephrine (NE) as NT

• NT in both PNS and CNS.

• PNS:
– Smooth muscles, cardiac muscle and glands.
• Increase in blood pressure, constriction of arteries.
• CNS:
– General behavior.
 Amino Acids as NT

• Glutamic acid and aspartic acid:

– Major excitatory NTs in CNS.
• Glutamic acid:
– NMDA receptor involved in memory storage.
• Glycine:
– Inhibitory, produces IPSPs.
– Opening of Cl- channels in postsynaptic membrane.
• Hyperpolarization.
– Helps control skeletal movements.
• GABA (gamma-aminobutyric acid):
– Most prevalent NT in brain.
– Inhibitory, produces IPSPs.
• Hyperpolarizes postsynaptic membrane.
– Motor functions in cerebellum.
 Polypeptides as NT

• CCK:
– Promote satiety following meals.
• Substance P:
– Major NT in sensations of pain.
• Synaptic plasticity (neuromodulating
effects):
– Neurons can release classical NT or the
polypeptide NT.
 Polypeptides as NT

• Endogenous opiods:
– Brain produces its own analgesic endogenous morphine-like
compounds, blocking the release of substance P.
– Beta-endorphin, enkephalins, dynorphin.
• Neuropeptide Y:
– Most abundant neuropeptide in brain.
– Inhibits glutamate in hippocampus.
– Powerful stimulator of appetite.
• NO:
– Exerts its effects by stimulation of cGMP.
– Macrophages release NO to helps kill bacteria.
– Involved in memory and learning.
– Smooth muscle relaxation.
 Endogenous Cannabinoids, Carbon
Monoxide

• Endocannabinoids:
– Bind to the same receptor as THC.
– Act as analgesics.
– Function as retrograde NT.
• Carbon monoxide:
– Stimulate production of cGMP within neurons.
– Promotes odor adaptation in olfactory neurons.
– May be involved in neuroendocrine regulation in
hypothalamus.
 EPSP

• No threshold.
• Decreases resting
membrane
potential.
– Closer to threshold.
• Graded in
magnitude.
• Have no refractory
period.
• Can summate.
 Synaptic Integration

• EPSPs can summate,

producing AP.
– Spatial summation:
• Numerous boutons
converge on a single
postsynaptic neuron
(distance).
– Temporal summation:
• Successive waves of
neurotransmitter
release (time).
 Long-Term Potentiation

• May favor transmission along frequently used

neural pathways.
• Neuron is stimulated at high frequency, enhancing
excitability of synapse.
– Improves efficacy of synaptic transmission.
• Neural pathways in hippocampus use glutamate,
which activates NMDA receptors.
– Involved in memory and learning.
 Synaptic Inhibition
• Presynaptic inhibition:
– Amount of excitatory NT
released is decreased by effects
of second neuron, whose axon
makes synapses with first
neuron’s axon.
• Postsynaptic inhibition
• (IPSPs):
– No threshold.
– Hyperpolarize postsynaptic
membrane.
– Increase membrane potential.
– Can summate.
– No refractory period.
 CNS

• Consists of:
– Brain.
– Spinal cord.
• Receives input from
sensory neurons.
• Directs activity of motor
neurons.
• Association neurons
maintain homeostasis in
the internal environment.
 Embryonic Development

• Groove appears in ectoderm to fuse to form neural tube by 20th

day after conception. Neural tube eventually forms the CNS.
• During 5th week, modified:
– Forebrain: telencephalon and diencephalon.
– Midbrain: unchanged.
– Hindbrain: metencephalon and myelencephalon.
• Part of ectoderm where fusion occurs becomes neural crest.
– Neural crest forms ganglia of PNS.
Embryonic Development (continued)
 Embryonic Development (continued)

• Telencephalon grows disproportionately forming 2

the hemispheres of the cerebrum.
• Ventricles and central canal become filled with
cerebral spinal fluid (CSF).
• CNS composed of gray and white matter.
– Gray matter consists of neuron cell bodies and
dendrites.
– White matter (myelin) consists of axon tracts.
 Cerebrum

• Only structure of the telencephalon.

• Largest portion of brain (80% mass).
• Responsible for higher mental functions.
• Corpus callosum:
– Major tract of axons that functionally interconnects right
and left cerebral hemispheres.
Cerebrum (continued)
 Cerebral Cortex

• Characterized by numerous convolutions.

– Elevated folds: gyri.
– Depressed groves: sulci.
• Frontal lobe:
– Anterior portion of each cerebral hemisphere.
– Precentral gyri:
• Contains upper motor neurons.
• Involved in motor control.
• Body regions with the greatest number of motor
innervation are represented by largest areas of motor
cortex.
Cerebral Cortex (continued)
 Cerebral Cortex (continued)

• Parietal lobe:
– Primary area responsible for perception of
somatesthetic sensation.
– Body regions with highest densities of receptors
are represented by largest areas of sensory
cortex.
• Temporal lobe:
– Contain auditory centers that receive sensory
fibers from cochlea.
– Interpretation and association of auditory and
visual information.
 Cerebral Cortex (continued)

• Occipital Lobe:
– Primary area responsible for vision and
coordination of eye movements.
• Insula:
– Implicated in memory encoding.
– Integration of sensory information with visceral
responses.
– Coordinated cardiovascular response to stress.
 Visualizing the Brain

• X-ray computed tomography (CT):

– Complex computer manipulations of data obtained from x-ray
absorption by tissues of different densities.
• Soft tissue.
• Positron-emission tomography (PET):
– Radioisotopes that emit positrons are injected into blood stream.
• Collision of positron and electron result in emission of gamma rays.
– Pinpoint brain cells that are most active.
» Brain metabolism, drug distribution.

• Magnetic resonance imaging (MRI):

– Protons (H+) respond to magnetic field, which align the protons.
• Emit a radio-wave signal when stimulated.
– Brain function.
 Electroencephalogram (EEG)

• Measures synaptic
potentials produced at
cell bodies and
dendrites.
– Create electrical
currents.
• Used clinically do
diagnose epilepsy and
brain death.
 EEG Patterns
• Alpha:
– Recorded from parietal and occipital regions.
• Person is awake, relaxed, with eyes closed.
– 10-12 cycles/sec.
• Beta:
– Strongest from frontal lobes near precentral gyrus.
• Produced by visual stimuli and mental activity.
• Evoked activity.
– 13-25 cycles/sec.
• Theta:
– Emitted from temporal and occipital lobes.
• Common in newborn.
• Adult indicates severe emotional stress.
– 5-8 cycles/sec.
• Delta:
– Emitted in a general pattern.
• Common during sleep and awake infant.
• In awake adult indicate brain damage.
– 1-5 cycles/sec.
 EEG Sleep Patterns
• 2 types of EEG patterns during sleep:
– REM (rapid eye movement):
• Dreams occur.
• Low-amplitude, high-frequency oscillations.
• Similar to wakefulness (beta waves).
– Non-Rem (resting):
• High-amplitude, low-frequency waves (delta waves).
• Superimposed on these are sleep spindles:
– Waxing and waning bursts of 7-14 cycles/sec.
– Last for 1-3 sec.
 Basal Nuclei (basal ganglia)

• Masses of gray matter

composed of neuronal cell
bodies located deep within
white matter.
• Contain:
– Corpus striatum:
• Caudate nucleus.
• Lentiform nucleus:
– Putman and globus
pallidus.

• Functions in the control of

voluntary movements.
 Cerebral Lateralization

• Cerebral dominance:
– Specialization of one
hemisphere.
• Left hemisphere:
– More adept in language and
analytical abilities.
– Damage:
• Severe speech problems.
• Right hemisphere:
– Most adept at visuospatial
tasks.
– Damage:
• Difficulty finding way
around house.
 Language

• Broca’s area:
– Involves articulation of speech.
– In damage, comprehension of speech in unimpaired.
• Wernicke’s area:
– Involves language comprehension.
– In damage, language comprehension is destroyed, but speech is
rapid without any meaning.
• Angular gyrus:
– Center of integration of auditory, visual, and somatesthetic
information.
– Damage produces aphasias.
• Arcuate fasciculus:
– To speak intelligibly, words originating in Wernicke’s area must be
sent to Broca’s area.
• Broca’s area sends fibers to the motor cortex which directly controls
the musculature of speech.
 Emotion and Motivation

• Important in the neural basis of

emotional states are
hypothalamus and limbic
system.
• Limbic system:
– Group of forebrain nuclei and
fiber tracts that form a ring
around the brain stem.
• Center for basic emotional
drives.
• Closed circuit (Papez circuit):
– Fornix connects
hippocampus to
hypothalamus, which projects
to the thalamus which sends
fibers back to limbic system.
 Emotion and Motivation (continued)

– Areas or the hypothalamus and limbic system are

involved in feelings and behaviors.
– Aggression:
• Amygdala and hypothalamus.
– Fear:
• Amygdala and hypothalamus.
– Feeding:
• Hypothalamus (feeding and satiety centers).
– Sexual drive and behavior:
• Hypothalamus and limbic system.
– Goal directed behavior (reward and punishment):
• Hypothalamus and frontal cortex.
 Memory

• Short-term:
– Memory of recent events.
• Medial temporal lobe:
– Consolidates short term into long term
memory.
• Hippocampus is critical component of
memory.
• Acquisition of new information, facts and
events requires both the medial temporal
lobe and hippocampus.
 Long-Term Memory

• Consolidation of short-term memory into long-term

memory.
– Requires activation of genes, leading to protein synthesis and
formation of new synaptic connections.
• Altered postsynaptic growth of dendritic spines in area of contact.
• Cerebral cortex stores factual information:
– Visual memories lateralized to left hemisphere.
– Visuospatial information lateralized to right hemisphere.
• Prefrontal lobes:
– Involved in performing exact mathematical calculations.
• Complex, problem-solving and planning activities.
 Long-Term Potentiation

• Type of synaptic learning.

– Synapses that are 1st stimulated at high frequency will
subsequently exhibit increased excitability.
• In hippocampus, glutamate is NT.
– Requires activation of the NMDA receptors for glutamate.
• Glutamate and glycine or D-serine binding and partial
depolarization are required for opening of channels for Ca2+ and Na+.
• May also involve presynaptic changes:
– Binding of glutamate to NMDA receptors and simultaneous
depolarization, open receptor channels for Ca2+.
• Ca2+ causes long-term potentiation in postsynaptic neuron, release of
NO from postsynaptic neuron.
– NO acts as a retrograde messenger, causing release of NT.
 Neuronal Stem Cells in Learning and
Memory
• Neural stem cells:
– Cells that both renew themselves through mitosis and
produce differentiated neurons and neuroglia.
• Hippocampus has been shown to contain stem
cells (required for long-term memory).
• Neurogenesis:
– Production of new neurons.
• Indirect evidence that links neuogenesis in
hippocampus with learning and memory.
 Thalamus and Epithalamus
• Thalamus:
– Composes 4/5 of the diencephalon.
– Forms most of the walls of the 3rd ventricle.
– Acts as relay center through which all sensory information (except
olfactory) passes to the cerebrum.
• Lateral geniculate nuclei:
– Relay visual information.
• Medial geniculate nuclei:
– Relay auditory information.
• Intralaminar nuclei:
– Activated by many sensory modalities.
– Projects to many areas.
» Promotes alertness and arousal from sleep.
• Epithalamus contains:
– Choroid plexus where CSF is formed.
– Pineal gland which secretes melatonin.
 Hypothalamus

• Contains neural centers for hunger, thirst, and

body temperature.
• Contributes to the regulation of sleep,
wakefulness, emotions, sexual arousal, anger, fear,
pain, and pleasure.
• Stimulates hormonal release from anterior
pituitary.
• Produces ADH and oxytocin.
• Coordinates sympathetic and parasympathetic
reflexes.
 Pituitary Gland

• Posterior pituitary:
– Stores and releases ADH (vasopressin) and oxytocin.
• Hypothalamus produces releasing and inhibiting
hormones that are transported to anterior
pituitary.
– Regulate secretions of anterior hormones.
• Anterior pituitary:
– Regulates secretion of hormones of other endocrine
glands.
 Midbrain

• Contains:
– Corpora quadrigemina:
• Superior colliculi:
– Involved in visual reflexes.
• Inferior colliculi:
– Relay centers for auditory information.
– Cerebral peduncles:
• Composed of ascending and descending fiber tracts.
– Substantia nigra:
• Required for motor coordination.
– Red nucleus:
• Maintains connections with cerebrum and cerebellum.
– Involved in motor coordination.
 Hindbrain
• Metencephalon:
– Pons:
• Surface fibers connect to cerebellum,
and deeper fibers are part of motor and
sensory tracts.
• Contains several nuclei associated with
cranial nerves V, VI, VII.
• Contains the apneustic and
pneumotaxic respiratory centerss.
– Cerebellum:
• Receives input from proprioceptors.
• Participates in coordination of
movement.
• Necessary for motor learning,
coordinating different joints during
movement, and limb movements.
 Hindbrain (continued)

• Myelencephalon (medulla oblongata):

– All descending and ascending fiber tracts between
spinal cord and brain must pass through the medulla.
• Nuclei contained within the medulla include VIII, IX, X, XI, XII.
• Pyramids:
– Fiber tracts cross to contralateral side.
– Vasomotor center:
• Controls autonomic innervation of blood vessels.
– Cardiac control center:
• Regulates autonomic nerve control of heart.
– Regulates respiration with the pons.
 Reticular Formation

• Reticular Formation:
– Complex network of nuclei and nerve fibers within
medulla, pons, midbrain, thalamus and hypothalamus.
– Functions as the reticular activating system (RAS).
• Non specific arousal of cerebral cortex to incoming sensory
information.
 Ascending Spinal Tracts

• Convey sensory
information from
cutaneous receptors,
proprioceptors and
visceral receptors to
cerebral cortex.
• Sensory fiber tract
decussation may
occur in medulla or
spinal cord.
 Descending Spinal Tracts

• Pyramidal (corticospinal)
tracts descend directly
without synaptic
interruption from cerebral
cortex to spinal cord.
– Function in control of fine
movements that require
dexterity.
• Reticulospinal tracts
(extrapyramidal):
– Influence movement
indirectly.
• Gross motor movement.
 Cranial and Spinal Nerves

• Cranial nerves:
– 2 pairs arise from neuron cell bodies in forebrain.
– 10 pairs arise from the midbrain and hindbrain.
• Roman numerals refer to the order in which the nerves are
positioned from front of the brain to the back.
– Most are mixed nerves containing both sensory and motor fibers.
• Spinal nerves:
– 31 pairs grouped into 8 cervical, 12 thoracic, 5 lumbar, 5 sacral,
and l coccygeal.
– Mixed nerve that separates near the attachment of the nerve to
spinal cord.
• Produces 2 roots to each nerve.
– Dorsal root composed of sensory fibers.
– Ventral root composed of motor fibers.
 Reflex Arc

• Unconscious motor
response to a sensory
stimulus.
• Stimulation of sensory
receptors evokes APs that
are conducted into spinal
cord.
– Synapses with
association neuron,
which synapses with
somatic motor neuron.
• Conducts impulses to
muscle and stimulates a
reflex contraction.
– Brain is not directly
involved.
 Neural Control of Involuntary Effectors

• Autonomic nervous system (ANS):

– Innervates organs whose functions are not
usually under voluntary control.
– Effectors include cardiac and smooth muscles
and glands.
• Effectors are part of visceral organs and blood
vessels.
 Autonomic Neurons

• 2 neurons in the
efferent pathway.
• 1st neuron has its cell
body in gray matter of
brain or spinal cord.
– Preganglionic neuron.
• Synapses with 2nd
neuron within an
autonomic ganglion.
– Postganglionic neuron.
• Autonomic ganglion has
axon which extends to
synapse with target
tissue.
 Autonomic Neurons (continued)

• Preganglionic autonomic fibers originate in

midbrain, hindbrain, and upper thoracic to 4th
sacral levels of the spinal cord.
• Autonomic ganglia are located in the head, neck,
and abdomen.
• Presynaptic neuron is myelinated and
postsynaptic neuron is unmyelinated.
• Autonomic nerves release NT that may be
stimulatory or inhibitory.
 Visceral Effector Organs

• Involuntary effectors are somewhat

independent of their innervation.
– Smooth muscles maintain resting tone in
absence of nerve stimulation.
• Denervation hypersensitivity:
– Damage to autonomic nerve makes its target tissue more
sensitive than normal to stimulating agents.
– Cardiac and many smooth muscles can
contract rhythmically in absence of nerve
stimulation.
 Divisions of the ANS

• Sympathetic nervous
system and para-
sympathetic nervous
system:
– Both have
preganglionic
neurons that
originate in CNS.
– Both have
postganglionic
neurons that
originate outside
of the CNS in
ganglia.
 Sympathetic Division

• Myelinated preganglionic fibers exit spinal cord in ventral roots

from T1 to L2 levels.
• Most sympathetic nerve fibers separate from somatic motor
fibers and synapse with postganglionic neurons within
paravertebral ganglia.
– Ganglia within each row are interconnected, forming a chain of ganglia
that parallels spinal cord to synapse with postganglionic neurons.
• Divergence:
– Preganglionic fibers branch to synapse with # of
postganglionic neurons.
• Convergence:
– Postganglionic neuron receives synaptic input from large # of
preganglionic fibers.
 Sympathetic Division (continued)

• Mass activation:
– Divergence and
convergence cause
the SNS to be
activated as a unit.
• Axons of
postganglionic
neurons are
unmyelinated to
the effector organ.
 Adrenal Glands

• Adrenal medulla secretes epinephrine (Epi) and

norepinephrine (NE) when stimulated by the sympathetic
nervous system.
• Modified sympathetic ganglion:
– Its cells are derived form the same embryonic tissue that forms
postganglionic sympathetic neurons.
• Sympathoadrenal system:
– Stimulated by mass activation of the sympathetic nervous system.
– Innervated by preganglionic sympathetic fibers.
 Parasympathetic Division

• Preganglionic fibers originate in

midbrain, medulla, pons; and in
the 2-4 sacral levels of the
spinal column.
• Preganglionic fibers synapse in
terminal ganglia located next to
or within organs innervated.
• Most parasympathetic fibers do
not travel within spinal nerves.
– Do not innervate blood
vessels, sweat glands, and
arrector pili muscles.
 Parasympathetic Division (continued)

• 4 of the 12 pairs of cranial nerves (III, VII, X, XI) contain

preganglionic parasympathetic fibers.
• III, VII, XI synapse in ganglia located in the head.
• X synapses in terminal ganglia located in widespread
regions of the body.
• Vagus (X):
– Innervates heart, lungs esophagus, stomach, pancreas,
liver, small intestine and upper half of the large
intestine.
• Preganglionic fibers from the sacral level innervate the
lower half of large intestine, the rectum, urinary and
reproductive systems.
 Sympathetic Effects

• Fight or flight response.

• Release of norepinephrine (NT) from
postganglionic fibers and epinephrine (NT) from
adrenal medulla.
• Mass activation prepares for intense activity.
– Heart rate (HR) increases.
– Bronchioles dilate.
– Blood [glucose] increases.
 Parasympathetic Effects

• Normally not activated as a whole.

– Stimulation of separate parasympathetic nerves.
• Release ACh as NT.
• Relaxing effects:
– Decreases HR.
– Dilates visceral blood vessels.
– Increases digestive activity.
 Adrenergic and Cholinergic Synaptic
Transmission

• ACh is NT for all preganglionic

fibers of both sympathetic
and parasympathetic nervous
systems.
• Transmission at these
synapses is termed
cholinergic:
– ACh is NT released by most
postganglionic
parasympathetic fibers at
synapse with effector.
• Axons of postganglionic
neurons have numerous
varicosities along the axon
that contain NT.
 Adrenergic and Cholinergic Synaptic
Transmission (continued)

• Transmission at these
synapses is called
adrenergic:
– NT released by most
postganglionic
sympathetic nerve fibers
is NE.
– Epi, released by the
adrenal medulla is
synthesized from the
same precursor as NE.
• Collectively called
catecholamines.
 Responses to Adrenergic Stimulation

• Beta adrenergic receptors:

– Produce their effects by stimulating production of cAMP.
– NE binds to receptor.
– G-protein dissociates into a subunit or bg- complex.
– Depending upon tissue, either a subunit or bg-complex
produces the effects.
• Alpha subunit activates adenylate cyclase, producing cAMP.
– cAMP activates protein kinase, opening ion channels.
 Responses to Adrenergic Stimulation
(continued)

• Alpha1 adrenergic receptors:

– Produce their effects by the production of Ca2+.
– Epi binds to receptor.
– Ca2+ binds to calmodulin.
– Calmodulin activates protein kinase, modifying enzyme
action.
• Alpha2 adrenergic receptors:
– Located on presynaptic terminal.
• Decreases release of NE.
– Negative feedback control.
– Located on postsynaptic membrane.
• When activated, produces vasoconstriction.
 Responses to Adrenergic Stimulation
(continued)

• Has both excitatory and inhibitory effects.

• Responses due to different membrane
receptor proteins.
– a1 : constricts visceral smooth muscles.
– a2 : contraction of smooth muscle.
– b1 : increases HR and force of contraction.
– b2 : relaxes bronchial smooth muscles.
– b3: adipose tissue, function unknown.
 Responses to Cholinergic Stimulation
• All somatic motor neurons, all preganglionic and
most postganglionic parasympathetic neurons are
cholinergic.
– Release ACh as NT.
– Somatic motor neurons and all preganglionic
autonomic neurons are excitatory.
– Postganglionic axons, may be excitatory or inhibitory.
• Muscarinic receptors:
– Ach binds to receptor.
– Requires the mediation of G-proteins.
– bg-complex affects opening or closing a channel, or
activating enzymes.
 Responses to Cholinergic Stimulation
(continued)

• Nicotinic receptors (ligand-gated):

– ACh binds to 2 nicotinic receptor binding sites.
– Causes ion channel to open within the receptor
protein.
• Opens a Na+ channel.
• Always excitatory.
Responses to Cholinergic Stimulation
(continued)
 Other Autonomic NTs

• Certain nonadrenergic, noncholinergic

postganglionic autonomic axons produce their
effects through other NTs.
– ATP.
– VIP.
– NO.
 Organs With Dual Innervation

• Most visceral organs receive dual innervation (innervation by

both sympathetic and parasympathetic fibers).
• Antagonistic effects:
– Sympathetic and parasympathetic fibers innervate the same cells.
• Actions counteract each other.
– Heart rate.

• Complementary:
– Sympathetic and parasympathetic stimulation produces similar effects.
• Salivary gland secretion.
• Cooperative:
– Sympathetic and parasympathetic stimulation produce different effects
that work together to produce desired effect.
• Micturition.
 Organs Without Dual Innervation

• Regulation achieved by increasing or decreasing

firing rate.
• Adrenal medulla, arrector pili muscle, sweat
glands, and most blood vessels receive only
sympathetic innervation.
– Nonshivering thermogenesis.
 Control of the ANS by Higher Brain Centers

• Sensory input transmitted to brain centers that integrate

information.
• Can modify activity of preganglionic autonomic neurons.
• Medulla:
– Most directly controls activity of autonomic system.
– Location of centers for control of cardiovascular, pulmonary, urinary,
reproductive and digestive systems.
• Hypothalamus:
– Regulates medulla.
• Cerebral cortex and limbic system:
– Responsible for visceral responses that are characteristic of
emotional states.
 Endocrine Glands and Hormones

• Secrete biologically
active molecules into
the blood.
– Lack ducts.
• Carry hormones to
target cells that
contain specific
receptor proteins for
that hormone.
• Target cells can
respond in a specific
fashion.
 Endocrine Glands and Hormones (continued)

• Neurohormone:
– Specialized neurons that secrete chemicals into the blood
rather than synaptic cleft.
• Chemical secreted is called neurohormone.
• Hormones:
– Affect metabolism of target organs.
• Help regulate total body metabolism, growth, and reproduction.
 Chemical Classification of Hormones

• Amines:
– Hormones derived from tyrosine and tryptophan.
• NE, Epi, T4.
• Polypeptides and proteins:
– Polypeptides:
• Chains of < 100 amino acids in length.
– ADH.
– Protein hormones:
• Polypeptide chains with > 100 amino acids.
– Growth hormone.
 Chemical Classification of Hormones
(continued)

• Lipids derived from cholesterol.

– Are lipophilic hormones.
• Testosterone.
• Estradiol.
• Cortisol.
• Progesterone.
Chemical Classification of Hormones
(continued)
 Chemical Classification of Hormones (continued)

• Glycoproteins:
– Long polypeptides (>100) bound to 1 or more carbohydrate
(CHO) groups.
• FSH and LH.
• Hormones can also be divided into:
– Polar:
• H20 soluble.
– Nonpolar (lipophilic):
• H20 insoluble.
– Can gain entry into target cells.
– Steroid hormones and T4.
– Pineal gland secretes melatonin:
• Has properties of both H20 soluble and lipophilic hormones.
 Prohormones and Prehormones

• Prohormone:
– Precursor is a longer chained polypeptide that is cut
and spliced together to make the hormone.
• Proinsulin.
• Preprohormone:
– Prohormone derived from larger precursor molecule.
• Preproinsulin.
• Prehormone:
– Molecules secreted by endocrine glands that are
inactive until changed into hormones by target cells.
• T4 converted to T3.
Common Aspects of Neural and Endocrine
Regulation
• APs are chemical events produced by diffusion of ions
through neuron plasma membrane.
• Action of some hormones are accompanied by ion
diffusion and electrical changes in the target cell.
– Nerve axon boutons release NTs.
– Some chemicals are secreted as hormones, and also are NTs.
• In order for either a NT or hormone to function in
physiological regulation:
– Target cell must have specific receptor proteins.
– Combination of the regulatory molecule with its receptor proteins
must cause a specific sequence of changes.
– There must be a mechanism to quickly turn off the action of a
regulator.
 Hormonal Interactions

• Synergistic:
– Two hormones work together to produce a
result.
– Additive:
• Each hormone separately produces response,
together at same concentrations stimulate even
greater effect.
– NE and Epi.
– Complementary:
• Each hormone stimulates different step in the
process.
– FSH and testosterone.
 Hormonal Interactions (continued)

– Permissive effects:
• Hormone enhances the responsiveness of a target
organ to second hormone.
– Increases the activity of a second hormone.
» Prior exposure of uterus to estrogen induces formation of
receptors for progesterone.

– Antagonistic effects:
• Action of one hormone antagonizes the effects of
another.
– Insulin and glucagon.
 Effects of [Hormone] on Tissue
Response
• [Hormone] in blood reflects the rate of secretion.
• Half-life:
– Time required for the blood [hormone] to be reduced to
½ reference level.
• Minutes to days.
• Normal tissue responses are produced only when
[hormone] are present within physiological range.
• Varying [hormone] within normal, physiological
range can affect the responsiveness of target cells.
 Effects of [Hormone] on Tissue
Response (continued)

• Priming effect (upregulation):

– Increase number of receptors formed on target cells in
response to particular hormone.
– Greater response by the target cell.
• Desensitization (downregulation):
– Prolonged exposure to high [polypeptide hormone].
• Subsequent exposure to the same [hormone] produces less
response.
– Decrease in number of receptors on target cells.
» Insulin in adipose cells.
– Pulsatile secretion may prevent downregulation.
 Mechanisms of Hormone Action
• Hormones of same chemical class have
similar mechanisms of action.
– Similarities include:
• Location of cellular receptor proteins depends on
the chemical nature of the hormone.
• Events that occur in the target cells.
• To respond to a hormone:
– Target cell must have specific receptors for that
hormone (specificity).
• Hormones exhibit:
– Affinity (bind to receptors with high bond strength).
– Saturation (low capacity of receptors).
 Hormones That Bind to Nuclear Receptor
Proteins

• Lipophilic steroid and

thyroid hormones are
attached to plasma carrier
proteins.
– Hormones dissociate from
carrier proteins to pass
through lipid component of
the target plasma
membrane.
• Receptors for the
lipophilic hormones are
known as nuclear
hormone receptors.
 Nuclear Hormone Receptors

• Steroid receptors are located in cytoplasm and in the

nucleus.
• Function within cell to activate genetic transcription.
– Messenger RNA directs synthesis of specific enzyme proteins that
change metabolism.
• Each nuclear hormone receptor has 2 regions:
– A ligand (hormone)-binding domain.
– DNA-binding domain.
• Receptor must be activated by binding to hormone before
binding to specific region of DNA called HRE (hormone
responsive element).
– Located adjacent to gene that will be transcribed.
 Mechanisms of Steroid Hormone Action

• Cytoplasmic receptor
binds to steroid hormone.
• Translocates to nucleus.
• DNA-binding domain
binds to specific HRE of
the DNA.
• Dimerization occurs.
– Process of 2 receptor units
coming together at the 2
half-sites.
• Stimulates transcription of
particular genes.
 Mechanism of Thyroid Hormone Action

• T4 passes into cytoplasm and is

converted to T3.
• Receptor proteins located in
nucleus.
– T3 binds to ligand-binding
domain.
– Other half-site is vitamin A
derivative (9-cis-retinoic) acid.
• DNA-binding domain can then
bind to the half-site of the
HRE.
– Two partners can bind to the
DNA to activate HRE.
• Stimulate transcription of
genes.
 Hormones That Use 2nd Messengers

• Hormones cannot pass through plasma

membrane use 2nd messengers.
– Catecholamine, polypeptide, and glycoprotein
hormones bind to receptor proteins on the target
plasma membrane.
• Actions are mediated by 2nd messengers
(signal-transduction mechanisms).
– Extracellular hormones are transduced into
intracellular 2nd messengers.
 Adenylate Cyclase-cAMP
• Polypeptide or glycoprotein hormone binds
to receptor protein causing dissociation of a
subunit of G-protein.
• G-protein subunit binds to and activates
adenylate cyclase.
• ATP cAMP + PPi
• cAMP attaches to inhibitory subunit of
protein kinase.
• Inhibitory subunit dissociates and activates
protein kinase.
 Adenylate Cyclase-cAMP (continued)

• Phosphorylates
enzymes within the cell
to produce hormone’s
effects.
• Modulates activity of
enzymes present in the
cell.
• Alters metabolism of
the cell.
• cAMP inactivated by
phosphodiesterase.
– Hydrolyzes cAMP to
inactive fragments.
 Phospholipase-C-Ca2+

• Binding of Epi to a-adrenergic receptor in

plasma membrane activates a G-protein
intermediate, phospholipase C.
– Phospholipase C splits phospholipid into IP3
and DAG.
• Both derivatives serve as 2nd messengers.
• IP3 diffuses through cytoplasm to ER.
– Binding of IP3 to receptor protein in ER causes
Ca2+ channels to open.
 Phospholipase-C-Ca2+ (continued)

• Ca2+ diffuses into

the cytoplasm.
– Ca2+ binds to
calmodulin.
• Calmodulin
activates specific
protein kinase
enzymes.
– Alters the
metabolism of the
cell, producing the
hormone’s effects.
Epi Can Act Through Two 2nd Messenger
Systems
 Tyrosine Kinase

• Insulin receptor consists of 2 units that dimerize when

they bind with insulin.
– Insulin binds to ligand–binding site on plasma membrane,
activating enzymatic site in the cytoplasm.
• Autophosphorylation occurs, increasing tyrosine kinase
activity.
• Activates signaling molecules.
– Stimulate glycogen, fat and protein synthesis.
– Stimulate insertion of GLUT-4 carrier proteins.
Tyrosine Kinase (continued)
 Pituitary Gland

• Pituitary gland is
located in the
diencephalon.
• Structurally and
functionally
divided into:
– Anterior lobe.
– Posterior lobe.
 Pituitary Gland (continued)

• Anterior pituitary:
– Master gland (adenohypophysis).
– Derived from a pouch of epithelial tissue that migrates
upward from the mouth.
• Consists of 2 parts:
– Pars distalis: anterior pituitary.
– Pars tuberalis: thin extension in contact with the infundibulum.
• Posterior pituitary(neurohypophysis):
– Formed by downgrowth of the brain during fetal
development.
– Is in contact with the infundibulum.
• Nerve fibers extend through the infundibulum.
 Pituitary Hormones

• Anterior Pituitary:
– Trophic effects:
• High blood
[hormone] causes
target organ to
hypertrophy.
• Low blood
[hormone] causes
target organ to
atrophy.
 Pituitary Hormones (continued)

• Posterior pituitary:
– Stores and releases 2 hormones that are produced
in the hypothalamus:
• Antidiuretic hormone (ADH/vasopressin):
– Promotes the retention of H20 by the kidneys.
» Less H20 is excreted in the urine.
• Oxytocin:
– Stimulates contractions of the uterus during parturition.
– Stimulates contractions of the mammary gland alveoli.
» Milk-ejection reflex.
 Hypothalamic Control of Posterior Pituitary

• Hypothalamus neuron
cell bodies produce:
– ADH: supraoptic nuclei.
– Oxytocin:
paraventricular nuclei.
• Transported along the
hypothalamo-
hypophyseal tract.
• Stored in posterior
pituitary.
• Release controlled by
neuroendocrine
reflexes.
 Hypothalamic Control of the Anterior
Pituitary

• Hormonal control rather

than neural.
• Hypothalamus neurons
synthesize releasing and
inhibiting hormones.
• Hormones are transported
to axon endings of median
eminence.
• Hormones secreted into the
hypothalamo-hypophyseal
portal system regulate the
secretions of the anterior
pituitary
 Feedback Control of the Anterior
Pituitary

• Anterior pituitary and hypothalamic secretions

are controlled by the target organs they regulate.
– Secretions are controlled by negative feedback
inhibition by target gland hormones.
• Negative feedback at 2 levels:
– The target gland hormone can act on the
hypothalamus and inhibit secretion of releasing
hormones.
– The target gland hormone can act on the anterior
pituitary and inhibit response to the releasing
hormone.
 Feedback Control of the Anterior Pituitary
(continued)

• Short feedback loop:

– Retrograde transport of
blood from anterior
pituitary to the
hypothalamus.
• Hormone released by
anterior pituitary inhibits
secretion of releasing
hormone.
• Positive feedback effect:
– During the menstrual
cycle, estrogen stimulates
“LH surge.”
 Higher Brain Function and Pituitary Secretion

• Axis:
– Relationship between anterior pituitary and a
particular target gland.
• Pituitary-gonad axis.
• Hypothalamus receives input from higher
brain centers.
– Psychological stress affects:
• Circadian rhythms.
• Menstrual cycle.
 Adrenal Glands

• Paired organs that cap the kidneys.

• Each gland consists of an outer cortex and inner
medulla.
• Adrenal medulla:
– Derived from embryonic neural crest ectoderm
(same tissue that produces the sympathetic
ganglia).
– Synthesizes and secretes:
• Catecholamines (mainly Epi but some NE).
 Adrenal Glands (continued)

• Adrenal cortex:
– Does not receive
neural innervation.
– Must be stimulated
hormonally (ACTH).
• Consists of 3 zones:
– Zona glomerulosa.
– Zona fasciculata.
– Zona reticularis.
• Secretes
corticosteroids.
 Functions of the Adrenal Cortex

• Zona glomerulosa:
– Mineralcorticoids (aldosterone):
• Stimulate kidneys to reabsorb Na+ and secrete K+.
• Zona fasciculata:
– Glucocorticoids (cortisol):
• Inhibit glucose utilization and stimulate
gluconeogenesis.
• Zona reticularis (DHEA):
– Sex steroids:
• Supplement sex steroids.
Functions of the Adrenal Cortex (continued)
 Functions of the Adrenal Medulla

• Innervated by preganglionic sympathetic

axons.
– Increase respiratory rate.
– Increase HR and cardiac output.
– Vasoconstrict blood vessels, thus increasing
venous return.
– Stimulate glycogenolysis.
– Stimulate lipolysis.
 Stress and the Adrenal Gland

• Non-specific response
to stress produces the
general adaptation
syndrome (GAS).
• Alarm phase:
– Adrenal glands activated.
• Stage of resistance:
– Stage of readjustment.
• Stage of exhaustion:
– Sickness and/or death if
readjustment is not
complete.
 Thyroid Hormones

• Thyroid gland is located

just below the larynx.
• Thyroid is the largest of
the pure endocrine
glands.
• Follicular cells secrete
thyroxine.
• Parafollicular cells secrete
calcitonin.
 Production of Thyroid Hormones

• Iodide (I-) actively transported into the follicle and

secreted into the colloid.
• Oxidized to iodine (Io).
• Iodine attached to tyrosine within thyroglobulin
chain.
– Attachment of 1 iodine produces monoiodotyrosine
(MIT).
– Attachment of 2 iodines produces diiodotyrosine (DIT).
• MIT and DIT or 2 DIT molecules coupled together.
 Production of Thyroid Hormones (continued)

• T3 and T4 produced.
• TSH stimulates pinocytosis into the follicular
cell.
– Enzymes hydrolyze T3 and T4 from thyroglobulin.
• Attached to TBG and released into blood.
Production of Thyroid Hormones (continued)
 Actions of T3

• Stimulates protein synthesis.

• Promotes maturation of nervous system.
• Stimulates rate of cellular respiration by:
– Production of uncoupling proteins.
– Increase active transport by Na+/K+ pumps.
– Lower cellular [ATP].
• Increases metabolic heat.
• Increases metabolic rate.
– Stimulates increased consumption of glucose, fatty acids
and other molecules.
 Diseases of the Thyroid

• Iodine-deficiency
(endemic) goiter:
– Abnormal growth of
the thyroid gland.
• In the absence of
sufficient iodine, cannot
produce adequate
amounts of T4 and T3.
– Lack of negative
feedback inhibition.
» Stimulates TSH,
which causes
abnormal
growth.
 Diseases of the Thyroid (continued)

[Iodine-deficiency (endemic) goiter—continued]

– Adult myxedema:
• Accumulation of mucoproteins and fluid in subcutaneous tissue.
– Symptoms:
• Decreased metabolic rate.
• Weight gain.
• Decreased ability to adapt to cold.
• Lethargy.

• Grave’s disease:
– Autoimmune disorder:
• Exerts TSH-like effects on thyroid.
– Not affected by negative feedback.
• Cretinism:
– Hypothyroid from end of 1st trimester to 6 months postnatally.
• Severe mental retardation.
 Parathyroid Glands

• Embedded in the lateral lobes

of the thyroid gland.
• Parathyroid hormone (PTH):
– Only hormone secreted by the
parathyroid glands.
• Single most important
hormone in the control of
blood [Ca2+].
• Stimulated by decreased blood
[Ca2+].
• Promotes rise in blood [Ca2+] by
acting on bones, kidney and
intestines.
 Pancreatic Islets (Islets of Langerhans)

• Alpha cells secrete glucagon.

– Stimulus is decrease in blood
[glucose].
– Stimulates glycogenolysis and
lipolysis.
– Stimulates conversion of fatty
acids to ketones.
• Beta cells secrete insulin.
– Stimulus is increase in blood
[glucose].
– Promotes entry of glucose into
cells.
– Converts glucose to glycogen
and fat.
– Aids entry of amino acids into
cells.
 Pineal Gland

• Secretes melatonin:
– Production stimulated by the suprachiasmatic nucleus (SCN) in
hypothalamus.
• SCN is primary center for circadian rhythms.
• Light/dark changes required to synchronize.
• Melatonin secretion increases with darkness and peaks in middle of
night.
– May inhibit GnRH.
– May function in the onset of puberty (controversial).
Pineal Gland (continued)
 Thymus

• Site of production of T cells (thymus-dependent

cells), which are lymphocytes.
– Lymphocytes are involved in cell-mediated immunity.
• Secretes hormones that are believed to stimulate T
cells after leave thymus.
– Thymus gland size is large in newborns and children.
• Regresses after puberty and becomes infiltrated with
strands of fibrous tissue.
 Gonads and Placenta

• Gonads (testes and ovaries):

– Secrete sex hormones.
• Testosterone.
• Estradiol 17-b.
– After menopause, produces estrone.
• Progesterone.
• Placenta:
– Secretes large amounts of estriol, progesterone,
hCG, hCS.
 Autocrine and Paracrine Regulation

• Autocrine:
– Produced and act within the same tissue of an organ.
• All autocrine regulators control gene expression in target cells.
• Paracrine:
– Produced within one tissue and regulate a different tissue of the
same organ.
• Cytokines (lymphokines):
– Regulate different cells (interleukins) .
• Growth factors:
– Promote growth and cell division in any organ.
• Neutrophins:
– Guide regenerating peripheral neurons.
 Prostaglandins

• Most diverse group of autocrine regulators.

• Produced in almost every organ.
• Wide variety of functions.
• Different prostaglandins may exert antagonistic
effects in some tissues.
– Immune system:
• Promote inflammatory process.
– Reproductive system:
• Play role in ovulation.
– Digestive system:
• Inhibit gastric secretion.
Prostaglandins (continued)
 Prostaglandins (continued)

– Respiratory system:
• May bronchoconstrict or bronchodilate.
– Circulatory system:
• Vasoconstrictors or vasodilators.
– Urinary system:
• Vasodilation.
• Inhibitors of prostaglandin synthesis:
– Non-steroidal anti-inflammatory drugs (NSAIDS).
• Aspirin, indomethacin, ibuprofen: inhibit COX1.
– Celecoxib and rofecoxib: inhibit COX2.