Physiology Lecture Outline: Central and Peripheral Nervous Systems

The nervous system is anatomically divided into two parts, the Central Nervous System (the brain and the spinal cord) and the Peripheral Nervous System (ganglia, 12 pairs of cranial nerves and 31 of pairs spinal nerves). We have been introduced to the concept of homeostasis in physiology, that is, the maintenance of a stable internal environment. A recurrent theme in physiology is how homeostasis is maintained by feedback loops, covered in the first section of this course. As a part of the feedback loop mechanism of control, the Central Nervous System (CNS) often plays a significant role as the integration center. This gives you the notion that it is for information processing, analysis and interpretation. The CNS is responsible for intricate and complex neuronal processing, with each region of the brain and spinal cord having distinct physiological functions. First, we will consider some of the general and more specific roles of various areas of the brain. The functions of the spinal cord are covered in the lab and lab manual. We will then cover the Peripheral Nervous System (PNS). The PNS can be divided into two parts, the Somatic Nervous System (SNS) and the Autonomic Nervous System (ANS). The SNS is responsible for movement of the body (soma = body), and its effector tissue is skeletal muscle. The ANS is responsible for automated responses that occur in the body (e.g., heart rate) and the effector tissues are cardiac muscle, smooth muscle and glands.

The Central Nervous System: The Brain

We can divide the brain into six parts in terms of physiological functions: 1. Cerebrum; 2. Hypothalamus; 3. Midbrain; 4. Cerebellum; 5. Pons; and 6. Medulla oblongata.

1. Cerebrum - This is the most developed area of brain in the human species and is considered to be
the center of the highest functions. The major functions include: awareness of sensory perception; voluntary control of movement (regulation of skeletal muscle movement); language; personality traits; sophisticated mental activities such as thinking, memory, decision making, predictive ability, creativity and self-consciousness. We will examine 4 lobes of the cerebrum. The Frontal Lobe - Concerned with higher intellectual functions and is involved in the many behavioral aspects of humans. It inhibits certain primitive behaviors. The Primary motor cortex controls the movement of the rest of the body while the premotor cortex just adjacent to it is concerned with the initiation, activation, and performance of the actual movement. The Parietal Lobe - This lobe is primarily concerned with the interpretation and integration of sensory inputs. The Somatosensory cortex is associated with reception and perception of touch, vibration, and position sense of the body. The Temporal Lobe - The temporal lobe contains the auditory cortex - for the reception and interpretation of sound information, and the olfactory cortex - for the sense of smell. It also houses the language cortex in the dominant hemisphere (usually the left hemisphere) and participates in recognition and interpretation of language.

2 The Occipital Lobe - This lobe contains the primary visual cortex for visual information interpretation. Degenerative conditions in specific regions can cause problems in fine motor control. Parkinson's disease is characterize by slow jerky movements; tremors of the face and hands; muscle rigidity; and great difficulty initiating voluntary movements. In Parkinson's disease, an overactive region acts like a stuck brake, continuously inhibiting the motor cortex. The disease results from the degeneration of a region called the substantia nigra, in particular dompaminergic neurons (those using the neurotransmitter dopamine) in this region. Huntington's disease involves an over stimulation of motor activities, such that limbs jerk uncontrollably. The Limbic system is a group of structures on the medial aspect of each hemisphere and diencephalon and is more a functional system than an anatomical one. The limbic system is the "emotional brain", participating in the creation of emotional states such as fear, anger, pleasure, affection, arousal, etc. and processing vivid memories associated with those states. For example, the amygdala is central for processing fear and stimulates a sympathetic response. The amygdala enables us to recognize menacing facial expressions in others and to detect the precise gaze of someone who is looking at us. Cerebral Lateralization Although anatomically the two hemispheres of the cerebrum look very similar, functionally the two sides are different. Thus, the term lateralization is used to denote that each lobe has developed special functions that are not shared by other lobes. In general: Left side: Language, logic, analytical, sequential, verbal tasks, (holistic information processing). "Thinkers" Right side: Spatial perception, artistic and musical endeavors (fragmentary information processing). "Creators" Specific examples are most obvious in the function of speech and word recognition. For example, the primary cortical areas for language are Broca's area and Wernike's area. The Broca's area (in the left frontal lobe) is responsible for speaking ability, the mechanics of skeletal muscle control for verbal articulation (sound production). Wernicke's area (in the left juncture of parietal, temporal and occipital lobes) is concerned with language comprehension, that is, understanding the words that are read or heard. These exist on the left hemisphere only if you are left-brain dominant - as most people who are right handed are. There functional areas on the right side are different. For example, the emotional aspect of language is controlled in the opposite hemispheres. Opposite Broca's area is the affective language area, which gives intonation to words, in order to modify their meaning. The area opposite Wernicke's is concerned with recognizing the emotion content of another person's speech. Think of someone saying "Oh great" with true excitement versus "Oh great" with complete sarcasm! Same words, different meanings. Language disorders caused by damage to specific cortical areas are known as aphasias. Most aphasias are caused by strokes. A stroke can be defined as a "cardiovascular accident", this occurs when a blood vessel in the brain (a cerebral blood vessel) ruptures or is blocked by a clot. The result is that the region of the brain being supplied by that vessel is deprived of the O2 and glucose that neurons require constantly in order to function. Damage of the affected area can result. Important note regarding neuron physiology: As we know, every cell needs energy (E) to fight entropy (2 nd law of thermodynamics). Cellular energy is ATP and there are 2 ways to make ATP in the body, 1) with O2 (aerobically) and 2) without O2

3 (anaerobically). Neurons cannot make ATP anaerobically (without O 2), thus they need a constant supply of O2 in order to make ATP. Neurons also require glucose (with O 2) to make ATP. Unlike most other cells, they cannot use other molecules such as lipids and proteins as fuel for ATP production. Furthermore, they have no stores of glucose (like muscle tissue has), so they need a constant supply of both O2 and glucose. This is one reason why blood glucose levels are important and so closely regulated. Brain damage may result if this organ is deprived of its critical O 2 supply for more than 4 or 5 minutes or if its glucose supply is cut off for more than 10 to 15 minutes.

2. Epithalamus, Thalamus and Hypothalamus

The epithalamus contains the pineal gland, a hormone secreting endocrine structure. Under the influence of the hypothalamus, the pineal gland secretes the hormone melatonin, which prepares the body for the night-time stage of the sleep/wake cycle. The thalamus makes up about 80% of the diencephalon and is the main relay center for the various sensory and motor functions. The Hypothalamus controls and regulates many important functions of the body, including: 1) Control of the Autonomic Nervous System - adjusts, coordinates, and integrates the A.N.S. centers in the brain that regulate heart rate, blood pressure, bronchiole diameter, sweat glands, G.I. tract activity, etc. It does this via the Parasympathetic and Sympathetic divisions of the A.N.S. 2) Control of Emotional Responses - in association with the limbic system, it forms part of the emotional brain. Regions involved in fear, pleasure, rage and sex drive are located in the hypothalamus. 3) Regulation of Body Temperature - the body's thermostat and set point is located in the hypothalamus. There are also 2 centers in the hypothalamus that respond to changes in the set point. Heat-losing center: activation of this center causes sweating and cutaneous vasodilation. Heat-promoting center: activation of this center causes shivering and cutaneous vasoconstriction. 4) Regulation of Hunger and Thirst Sensations - hypothalamus contains the feeding and thirst centers. Feeding center: this center is always active and stimulates hunger which is 'fed' by eating. Satiety center: stimulated when satisfied, this inhibits the always hungry feeding center. Thirst center: osmoreceptors detect changes in osmotic pressure of blood, ECF, stimulate thirst. 5) Control of the Endocrine System - controls the release of pituitary hormones. Controls the anterior pituitary gland, when the hypothalamus releases hormones, it can stimulate or inhibit the release of other hormones form the pituitary (6 hormones). Also, it makes the 2 hormones (oxytocin and antidiuretic hormone (ADH)) that are stored in the posterior pituitary and released when signaled. All of these hormones regulate many other organs in the body.

3. Midbrain Portions receive visual input auditory input from the medulla oblongata and are involved
in cranial reflexes, e.g., when you turn your head if you thought you heard your name called out.

4. Cerebellum - Means little brain. The Cerebellum has two primary functions:
1) Controls postural reflexes of muscles in body - i.e., it coordinates rapid, automatic adjustments to maintain equilibrium, e.g. regaining your balance when you start to fall. 2) Produces skilled movements - involved in implementing routines for fine tuned movements. Controlled at the conscious and subconscious level, refines learned routines (e.g. driving, skating, playing an instrument) until the action becomes routine. This then reduces the need for conscious attention to the

4 task. The cerebellum gets incoming information from proprioceptors, a type of sensory receptor found in movable joints, tendons and muscle tissue. Using the information from proprioceptors in the body, the cerebellum can determine the relative position of various body parts and compares motor commands and intended movements with the actual position of the body part (legs, arms). In this way, it can perform any adjustments needed to changes the direction or make the movement (action) smooth and coordinated.

5. Pons - Plays a role in the regulation of the respiratory system. Contains two pontine respiratory
centers: 1) the pneumotaxic center and 2) the apneustic center. These two centers will be discussed later in the respiratory system. The pons is not responsible for the rhythm of breathing (the medulla oblongata is) but controls the changes in depth of breathing and the fine tuning of the rhythm of breathing set by the medulla oblongata. The pons also prevents over inflation of the lungs.

6. Medulla Oblongata
The medulla oblongata is the last division of the brain. It becomes continuous with the spinal cord. It houses some very important visceral or vital centers, 1) the cardiac center - adjusts the force and rate of the heartbeat; 2) the vasomotor center - regulates the diameter of blood vessels and therefore systemic blood pressure (constriction increases and dilation decrease blood pressure); and 3) the respiratory center - for control of the basic rhythm and rate of breathing. Additional centers regulate sneezing, coughing, hiccupping, swallowing and vomiting.

Spinal Cord
The physiology of the spinal cord will be covered in the lab component of this physiology course. The basic structure of the spinal cord is that it is the downward continuation of medulla oblongata starting at the foramen magnum. It descends to about the level of the second lumbar vertebra, tapering to a structure called the conus medullaris. The cord projects 31 pairs of spinal nerves on either side (8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 1 coccygeal) that are connected to the peripheral nerves. A cross section of the spinal cord exhibits the butterfly-shaped gray matter in the middle, surrounded by white matter. As in the cerebrum, the gray matter is composed of nerve cell bodies. The white matter consists of various ascending and descending tracts of myelinated axon fibers with specific functions. The spinal cord serves as a passageway for the ascending (going up) and descending (going down) fiber tracts that connect the peripheral and spinal nerves with the brain. Each of the 31 spinal segments is associated with a pair of dorsal root ganglia. These contain sensory nerve cell bodies. The axons from these sensory neurons enter the posterior aspect of the spinal cord via the dorsal root. The axons from somatic and visceral motor neurons leave the anterior aspect of the spinal cord via the ventral roots. Distal to each dorsal root ganglion the sensory and motor fibers combine to form a spinal nerve - these nerves are classified as mixed nerves because they contain both afferent (sensory) and efferent (motor) fibers.

The Cranial and Spinal Meninges

The delicate neural tissue of the brain and spinal cord is not only protected by the bones of the skull and vertebral column but also by layers of specialized membranes, called cranial and spinal meninges. Listed below are the 3 layers (from outer most to inner most) and the spaces they create. Bone; Epidural space; Dura mater; Subdural space; Arachnoid layer; Subarachnoid space; Pia mater and Nervous tissue.

5 Cerebrospinal Fluid Cerebrospinal fluid (CSF) flows within the ventricles of the brain, the central canal of the spinal cord and out to the subarachnoid spaces surrounding the brain and spinal cord. It serves as a medium for the transfer of substances between the blood and the nervous tissues as well as a liquid buffer, absorbing mechanical shocks to the brain or the cord. Most of CSF is provided by the choroid plexuses that reside in lateral, third and fourth ventricles. In adults, the total volume of this fluid has been calculated to be from 125 to 150 ml (4-5 oz). It is continuously formed, circulated and absorbed. Approximately 450 ml (nearly 2 cups) of CSF are produced every day, or 0.35 ml per minute in adults and 0.15 per minute in infants. The CSF circulates throughout the base of the brain, down around the spinal cord as well as upward over the cerebral hemispheres. The CSF is then absorbed primarily through arachnoid villi into the superior sagittal sinus and re-joins the blood circulation. The obstruction of the normal CSF flow or overproduction of CSF from a choroid plexus papilloma (a benign tumor of the choroid plexus) can lead to a condition known as hydrocephalus - an excessive accumulation of CSF in the ventricles or in the subarachnoid space. In newborns it results in an enlarged cranium, as the young skull bones are not yet fused and the infant cranial cavity can expand. In adults, however, it is typically accompanied by serious increase in intracranial pressure (ICP). Increased Intracranial Pressure The normal values for intracranial pressure (ICP) are approximately 90-210 mm Hg in adults and 15-80 mm Hg in infants. Increased ICP can occur as a result of an increased volume or mass within the limited space or volume of the cranium. Examples include an increase in CSF volume, cerebral edema, and growing mass lesions such as tumors and hematomas. Cerebral edema is the increase in brain tissue fluid causing swelling. It may occur secondary to head injury, infarction or a response to adjacent hematoma or tumor. Uncorrected increased ICP can lead to further brain damage due to the pressure and inadequate blood perfusion of neurological tissues. The treatment for increased ICP includes removing the mass (tumor, hematoma) by surgery, draining CSF from the ventricles by a drain or a shunt (plastic tube from ventricles to a vein in the neck), steroids, osmotic dehydrating agents and barbituates. The Peripheral Nervous System The central nervous system is connected to the peripheral nervous system by nerves. The PNS can be viewed as an extension of the CNS, connected to it by sensory and motor neurons and ganglion. The PNS can be divided into two parts, the Somatic Nervous System (SNS) and the Autonomic Nervous System (ANS). The SNS is responsible for movement of the body (soma = body), and its effector tissue is skeletal muscle. The ANS is responsible for automated responses that occur in the body (e.g., heart rate, blood pressure) and the effector tissues are cardiac muscle, smooth muscle and glands. The Somatic Nervous System The somatic nervous system is for the control of the skeletal muscle of the body, so essentially this means it controls body movement. For the most part this is voluntary, that is, it is under conscious control, you think about it first. In fact, the main region of the central nervous system that sends signals out to the SNS is located in the frontal lobe (the precentral sulcus). As we know from earlier, this is located in the cerebrum, which is the seat of the conscious mind. SNS Mode of Action Compared to the ANS, the SNS is very simple in its arrangement. There is one motor neuron from the CNS to innervate (have an effect on) one type of tissue, skeletal muscle.

6 At the junction between the neurons synaptic end bulb and the muscle cell, called the neuromuscular junction (NMJ), the somatic motor neuron releases the neurotransmitter acetylcholine (ACh). This diffuses across the NMJ and binds to nicotinic receptors on the plasma membrane of the skeletal muscle cell. As we shall see in the next section on skeletal muscle physiology, this causes the muscle to contract and generate force. As skeletal muscles are attached to bones and they span over moving joints, this contraction causes body movement. In general, the SNS is considered to be under voluntary control, but there is an important exception reflexes. By definition, a reflex is a rapid, automated, stereotyped response to a stimulus, usually to get the body out of danger. For example, think of how you might put your hand on something hot without realizing, but before you even perceive the hotness, you have automatically pulled your hand away from the potentially dangerous stimulus. This is called the withdrawal reflex and occurs without your conscious control. The SNS in Summary: # of Neurons: 1 motor neuron. Effector Tissue: Skeletal Muscle. Neurotransmitter: ACh. Receptors: Nicotinic. Action: Excites tissue causing contraction. Control: Voluntary (except reflexes). ANS Mode of Action The Autonomic Nervous System (ANS) has a more complex arrangement than the SNS. In involves two motor neuron, one from the CNS to a ganglion and the second motor neuron from the ganglion to the effector tissue. A ganglion is a cluster of nerve cell bodies outside of the CNS (or in the PNS). There are two divisions to the ANS, the Parasympathetic and the Sympathetic. Both divisions have the same effector tissues, which means they affect the same tissues in the body but they often have antagonistic or opposite effects. There are three categories of effector tissue n the ANS: 1) cardiac muscle, 2) smooth muscle, and 3) glandular tissues. PARA: In general the Parasympathetic division can initially be described by the phrases Rest and Digest or Feed and Breed. This simply means that this portion of the ANS is for housekeeping activities, putting things back in place, storing needed things and eliminating waste. For example, after lunch, when you sit down to read, the Parasympathetic division is at work. Your heart rate is lowered, your gastrointestinal tract activity is increased, increasing its mobility and secretions. The diameter of your bronchioles (airways) is small, as you dont need more air when your are sitting reading. The diameter of your pupils is also small, this enables the fine focus of your eyes for reading the pages in front of you. Now for the details! Of the two motor neurons, the first one is called the preganglionic neuron, as it is going to the ganglion and synapses with the second neuron called the postganglionic neuron, the one leaving the ganglion. At the ganglion for the Para division, the preganglionic neuron releases the neurotransmitter ACh and this diffuses across the synaptic cleft to bind to nicotinic receptors on the plasma membrane of the postsynaptic neuron. The effect is to excite the postsynaptic neuron to send a signal to the effector tissue from the second neuron. If this sounds familiar, it is because it is the same chemical arrangement as the neuromuscular junction of the somatic nervous system. The postganglionic neuron is the one that goes to the effector tissue, cardiac, smooth muscle or glands. Within the Para division, the postganglionic neuron releases ACh again, it diffuses across and binds to muscarinic receptors on the plasma membrane of the effector tissue. When muscarinic receptors are stimulated, they

7 often cause inhibition, thus we see the reduction of the heart rate, the reduction of bronchiole diameter, etc. SYM: In general the Sympathetic division can initially be described by the phrases Fight or Flight. This implies that this portion of the ANS is for emergency situations, for putting up your dukes and fighting, or running away either way it requires a lot of energy. If we stay with the example above, after lunch, lets say instead just as you sit down to read, a hungry bobcat enters the room. Immediately the Sympathetic division is at work. Your heart rate skyrockets (to pump more blood to body to get you out of danger), your gastrointestinal tract activity comes to a halt, and the diameter of your bronchioles (airways) is become larger, as you need much more air to either fight or run away. The diameter of your pupils also becomes larger, this enables distant focus of your eyes, so you can see an open window or some other escape route. Again, we will look at the details. The preganglionic neuron the both divisions (Para and Sym) function in exactly the same way, so we have already covered that above. The postganglionic neuron of the Sym division goes to the effector tissue as the Para division (cardiac, smooth muscle or glands). However, the Sym postganglionic neurons release norepinephrine (NE) and this diffuses across and binds to either or receptors on the plasma membrane of the effector tissue. These either or receptors on the will have various effects, depending on what tissue they are on. Overall, what will be seen is an increase in heart activity (therefore blood delivery to tissues in need), plus the increase in bronchiole diameter, pupil, etc. In the companion PNS worksheets (online), there is a diagram of the anatomical arrangement of both the Para and Sym divisions of the ANS. The ANS in Summary: # of Neurons: 2 motor neuron. Effector Tissue: Cardiac Muscle, Smooth Muscle and Glands. Neurotransmitter: ACh and NE. Receptors: a) Nicotinic and Muscarinic and b) and . Action: Parasympathetic usually clams things down and Sympathetic usually excites! Control: Involuntary (except biofeedback).

Central Nervous System

Peripheral Nervous System

Somatic Nervous System

Autonomic Nervous System

8 The table below is a sampling of some specific effector tissues of the ANS and how the Para and Sym divisions differ in their effect on this tissue. Please note, skeletal muscle is NOT an effector tissue of the ANS, though it is tempting to associated it with the sympathetic division of the ANS (when running away from that bobcat), skeletal muscle is the effector tissue of the Somatic Nervous System! The sympathetic does increase the blood flow to skeletal muscle, but does not control skeletal muscle itself.

The Autonomic Nervous System

Parasympathetic Stimulation Craniosacral origin Effector Tissue Heart Lung Bronchioles Iris (eye muscle) Salivary Glands G. I. Tract Activity Liver Kidney Adrenal Medulla (Adrenal gland) Arterioles and veins Bladder ACh acting on muscarinic receptors Heart rate decreased Bronchial constriction Pupil constriction Saliva production increased (watery increased) Secretions increased Motility increased No effect Increased urine secretion No effect No effect Wall contracted Sphincter relaxed Sympathetic Stimulation Thoracolumbar origin NE acting on and receptors Heart rate and force increased Bronchial dilation Pupil dilation Saliva production reduced (mucus increased) Secretions reduced Motility reduced Increased conversion of glycogen to glucose Decreased urine secretion Norepinephrine and epinephrine secreted Vasoconstriction - receptors Vasodilation - receptors Wall relaxed Sphincter closed