INTRODUCTION Animals are characterized by irritability or the ability to detect and respond to environmental stimuli. This involves a sensory system (detection), a nervous system (interpretation) and a motor system (response). The nervous system is thus a connection between sensory inputs and motor outputs. As evolution proceeded the nervous system becomes more complex. The radically symmetrical animals have simple nervous system consisting of nerve net work, conducts signals from sensory cells to muscle cells. There is no centralization of nervous system. The bilaterally symmetrical animals have centralized nervous system with enlarged anterior end called brain. The rest of which is the spinal cord. Generally, invertebrate animals tend to be small and have simple nervous system, whereas vertebrates have highly or well developed nervous system. Especially important is that all vertebrates have a similar basic structure of their nervous system that is divided into: (1) central nervous system (CNS) which comprises the brain and spinal cord. (2) Peripheral nervous system (PNS) which comprises cranial nerves that join the brain and nerves of the spinal cord (spinal nerves). Nervous system in fish and amphibians is poorly developed compared to higher vertebrates and the number of cranial nerves is ten pairs only. In reptiles and birds, the nervous system is more developed, as the brain increases in size and the number of cranial nerves increased by two pairs (spinal accessory and the hypoglossal). In mammals, the nervous system is more complicated than other vertebrates and is characterized by: (1) increased brain size relative to body size. (2) increased subdivisions and growth of forebrain, especially the cerebrum, which is associated with the increasingly complex behaviour of mammals. (3) cerebral cortex is present that is concerned with the muscular activity and higher brain functions. NERVOUS SYSTEM Life is maintained by coordination of the functions of various body systems. Coordination is controlled by two main systems: 1- Endocrine system (chemical regulation): is a collection of blood carrying chemical messengers (hormones) with slow and long standing action. 2-Nervous system (neural regulation): includes trillions of interconnected neurons with rapid and short standing action. FUNCTIONS OF NERVOUS SYSTEM: Nervous system acts to regulate and coordinate various body activities necessary to life by allowing us to receive stimuli (sensory information) from various sensory receptors and then processing them into appropriate responses made by body organs (effectors). NERVOUS TISSUE Nervous tissue is composed of two types of cells: (1) neurons or nerve cells (figure 1). (2) neuroglia (also called glia or glial cells "means glue"). Figure 1: The general structure of the neuron. GLIAL CELLS: The glial cells (figure 2) represent about 10 to 50 times the number of neurons and are in direct contact with neurons and often surround them. They act to support, nourish and protect the neurons, thus aid in their ability to do their functions. TYPES OF GLIAL CELLS: 1-Oligodendroglia: They are few macroglial cells that form myelin sheath around the axons in the CNS (like the Shwann cells in the PNS). A single cell can extend and surround large number of neurons for myelination of their axons. 2-Astroglia: They are the most abundant of glial cells that have star like appearance. Astroglia fill the spaces between neurons, have numerous projections that hold neurons to their blood supply and help to regulate the external chemical environment of neurons by removing excess ions (notably potassium). Also they take up neurotransmitters that are released by neurons during synaptic transmission and recycling them. 3-Microglia: They are of various forms that have branched processes. They are migratory and act as phagocytes to waste products of nerve tissues. Microglia originate outside the brain, mostly in bone marrow, unlike other glial cells. Figure 2: Types of glial cells. THE NEURON: The neuron is the structural or anatomical unit that is responsible for the functions normally associated with the nervous system. It operates by generating electrical signals that pass from one part of the cell to another part of the same cell and by releasing chemical messengers (neurotransmitters) to communicate with other cells. STRUCTURE OF THE NEURON: Neurons vary considerably in size and shape according to their sites and functions. In general, they are formed of the cell body and cell processes (figure 1). 1) The cell body (Soma): The cell body is the enlarged part of the neuron. It is a metabolic center that provides nutrition for the whole neuron. The cell bodies inside the CNS are usually collected into groups called (nuclei or centers), but in PNS usually collect to form (ganglia). The cell body is surrounded by the cell membrane which continues to cover its processes. The cell body contains nucleus and surrounding cytoplasm, besides mitochondria and other organells typical in eukaryotic cell, but no centrosomes. The absence of centrosomes indicates that the neurons have lost its power of division. In addition, the neuron contains specialized structures including: • Nissl bodies: these are granular materials (free and attached ribosomes) that present in the cell body and not present in dendrites or axon. Nissl bodies are responsible for synthesis of protein in the nerve cell. • Neurofibrils: these are thin fibers that present in the cell body and extend into the processes of the cell. They serve as a support of the neuron to maintain its shape. • Microtubules: these are distributed through out the cytoplasm of the cell body and extend into the dendrites and axon. They serve to support the neuron (as neurofibrils) and to transport materials and organells down from the cell body to the axon (axon transport), for regeneration of damaged axons. Axon transport of certain materials also occurs in the opposite direction from the axon terminals to the cell body. By this route, growth factors and other chemical signals picked up at the terminal can affect the neuron. This is also the route by which certain viruses taken up by the peripheral terminals can enter the CNS. 2) The Cell Processes: a) The dendrites: are multiple short processes which extend from the cell body. They extend to the surrounding area to act as receptive surface. So, the dendrites increase the surface area of the cell body. The surface of dendrites collect impulses and transmit them to the cell body. b) The axon (nerve fiber): is a single long process that conducts impulses away from the cell body to its target cell. Axons vary in length from only a millimeter to a meter or more (axons extending from spinal cord to foot). The portion of the axon closest to the cell body plus the part of the cell body where the axon is joined known as the initial segment or (axon hillock). It is important in generating the electric signal that propagates away from the cell body along the axon. The axon may have branches called collateral branches along its length (figure 1). Near the ends, both the axon and its collaterals undergo further branching. Each branch ends in a terminal, which makes junction with one of the following (figure 3): • Dendrites or cell body of another neuron, forming a (neuro-neural junction) or synapse. • Muscle fiber to form a (neuro-muscular junction). • Secretory gland to form a (neuro-epithelial junction). Figure 3: Termination of the axon MYELINE (MEDULLARY) SHEATH: All vertebrates have two types of nerve fibers, the large axons more than 1um in diameter being myelinated and those of smaller diameter are generally unmyelinated. Almost all invertebrates are equipped only with non-myelinated fibers, but some differ from those in the vertebrates in being much larger. Myelin is a white lipoprotein material composed of several compressed layers (20-200) which make successive wrappings around the axon. Myelin sheath is not a continuous layer, but is interrupted at regular internods by nodes of Ranvier (figure 4). Through these nodes, ions and water inside the neurons can undergo exchange with surrounding tissues. In PNS, myelin sheath is usually covered by a thin basement membrane (the neurilemma). Just beneath it, the Schwann cells are to be found at the mid point of each internode. In contrast, the nerve fibers within the central nervous system usually lack the neurilemma. In the CNS, myelin sheaths are formed by oligodendroglia (a type of glial cells), while in the PNS , Schwann cells are responsible for this . Each Schwann cell only warps an internode ( i.e many Schwann cells will myelinate one axon ), although one oligodendroglia will myelinate many axons in the CNS. This difference allows Schwann cells to act for regenerating damaged axons in PNS , but oligodendroglia can not guide regeneration and damage in CNS . It is therefore irreparable. Figure 4: Diagram of a part of vertebrate axon (ax.) showing myelin sheath (myel.), nodes of Ranvier (n.) and Schwann cell (S.c.) just beneath the neurilemma (N.) . TYPES OF NEURONS: I) STRUCTURAL CLASSIFICATION OF NEURONS: There are four types of neurons (figure 5) according to the number of processes extending from the cell body (polarity): 1) Unipolar neuron: Has only one process (exists in the nuclei of cranial nerves). 2) Pseudounipolar neuron: Has one short process that gives two branches . One is the long peripheral process ends at the receptor . The other branch is the short central process enters the central nervous system (exists in the spinal ganglia). 3) Bipolar neuron: Has one long axon and one dendrite on the opposite sides of the cell body (less common, exists in certain tissues as retina of eye, olfactory epithelium of the nose & in the ear). 4) Multipolar neuron: Has several short dendrites and one long axon (exists widely in brain & spinal cord). Figure 5: Types of neurons. (a) unipolar neuron, (b) pseudounipolar neuron (c) bipolar neuron and (d) multipolar neuron. II) FUNCTIONAL CLASSIFICATION OF NEURONS: 1-Sensory or afferent neurons: Conduct impulses from the sensory receptors to CNS. 2-Motor or efferent neurons: Conduct impulses from the CNS to effector organs. There are two types of motor neurons (Figure 6): a) Somatic motor neurons: which innervate external (voluntary) organs (skeletal muscles). b)Autonomic motor neurons: which innervate the internal (involuntary) organs (smooth and cardiac muscles and glands). 3- Interneurons (about 99% of all neurons): They connect sensory and motor neurons and serve to integrate functions of nervous system. Figure 6: The sensory- motor neurons. NOTE: • Motor and interneurons are multipolar, whereas sensory neurons are often unipolar. • For afferent neurons, both cell body and the long peripheral process of the axon are outside the CNS and only a part of the central process enters the brain or spinal cord. • The interneurons are located inside CNS. • For efferent neurons, the cell bodies are within the CNS, but the axons extend out into periphery. • The axons of both afferent and efferent neurons, except for the small parts in the brain or spinal cord, form the nerves (nerve trunks) of the PNS. THE NERVE: The nerve (or nerve trunk) is composed of a large number of nerve fibers. Each nerve fiber is an axon covered by a myelin sheath. The fibers are bound together in bundles by connective tissue rich in blood vessels known as perineurium.. Bundles of individual nerve fibers form the nerve trunk which is enclosed in a relatively strong sheath of connective tissue known as epineurium. REFLEX ACTION The activities controlled by the nervous system are called reflex actions or simply reflexes. The reflex is a reaction started by a change in the surrounding environment which acts as a stimulus, stimulating one of the receptors. This leads to initiation of nerve impulse which passes through chain of sensory neurons to CNS. From the CNS, impulses pass outwards (reflected) as a response through the motor neurons and reach the effector organ. REFLEX ARC: The reflex action is carried out through a pathway called reflex arc, which is considered the functional or (plysiological) unit of the nervous system. The reflex arc consists of: • A receptor organ: it is a sensory cell where stimulus is received. • A sensory (afferent) neuron: Its function is to conduct impulse from the receptor neuron to CNS. • An interneuron: The afferent neurons commonly synaptically communicate with interneurons, which in turn send impulses to motor neurons or to other interneurons, which finally influence the activity of the motor neurons concerned in the reflex action. • A motor (efferent) neuron: It serves to transmit the impulse to the effector organ. • An effector organ: It is the organ which responds to the transmitted impulse (e.g. the muscle or gland). The reflex arc in which the afferent sensory neurons directly communicate with the efferent motor neurons is a simple reflex arch with a single synapse (monosynaptic arc) and the reflex is monosynaptic reflex, while the reflex arc in which one or more interneurons are imposed between the afferent and efferent neurons are polysynaptic (No. of synapses in the arc varies from two to many hundreds). Figure 7: Reflex arc TYPES OF REFLEXES: The reflexes are functionally classified into: (1) The somatic reflexes. (2) The autonomic reflexes. In the two reflexes, the sensory pathway is similar, but the motor pathway differs. In the somatic reflex the motor (efferent) branch consists only of one motor neuron (its cell body located in CNS), while it consists of two neurons in the autonomic reflex. They are pre-ganglionic neuron with the cell body located in the CNS and post-ganglionic neuron with the cell body located in a ganglion (called autonomic ganglion) outside CNS (figure 8). Anatomically, reflexes are either: (a) spinal reflex, which concerned with immediate withdrawal from harmful stimuli (without involvement of brain) or (b) cranial reflex, which is more complicated reflex action (involves association of specific brain areas). Figure 8: Somatic and autonomic reflex arcs. Examples Of Reflexes: 1) The sudden withdrawal of one’s hand when it comes in contact with hot surface. 2) The act of sneezing and coughing (coughing is mainly due to irritation of the larynx by some materials, while sneezing is due to irritation of the mucous membrane of the nose). 3) The secretion of sweat in an increased quantity (warmth acts as the stimulus for increased secretion). 4) The secretion of saliva and gastric juice and the movements of the stomach (food acts as a stimulus). RECEPTORS: Are specialized endings of afferent (sensory) neurons or separate cells. Generally receptors are classified into two groups: Exteroceptors and Interoceptors. 1) Exteroceptors(for detection of external stimuli), they include: • Touch and pressure (cutaneous) receptors. • Thermal receptors. • Photoreceptors. • auditory receptors. • Smell and taste receptors (chemoreceptors). 2) Interoceptors (for detection of internal stimuli), they inclued: • Proprioceptors (respond to change in position of body). • Baroreceptors (respond to change in blood pressure). • Chemoreceptors (respond to change in circulating, CO2, O2 and H+). NERVE IMPULSE: The neurons (like all other cells) have difference in the concentration of ions on the two sides of their plasma membrane. Under resting condition, the major ions in the extracellular fluid are sodium and chloride ions, whereas the intercellular fluid contains high concentration of potassium ions and negatively charged nondiffusible organic molecules, particularly proteins and phosphates. This unequal distribution of ions and charges around the membrane results in a net negative charge inside and a positive charge outside the membrane (i.e. the membrane is polarized). This charge difference at rest, develops an electrical potential (resting membrane potential). In many nerve cells the resting membrane potential is approximately (– 0.06v) or (– 60 mv). Minus sign indicates that inside of the cell is more negative than the extracellular fluid. Sodium Potassium Pump : The concentration difference for sodium and potassium on the two sides of the cell is due to the action of plasma membrane active transport system (sodium – potassium pump) that maintains this unequal concentration by actively transporting ions against their concentration gradient using ATP. Sodium–potassium pump actually pumps three sodium ions out of the cell for every two potassium ions that they bring. This unequal transport of positive ions make the inside of the cell more negative than it would be from simple ions diffusion . The Action Potential (temporary change in the membrane potential): The nerve cell is especialized to respond to stimuli (change in the surrounding environment) and to convert this stimuli into electrical signal or nerve impulse that is conducted along the nerve fiber to its terminals. This occurs by the rapid changes in their resting membrane potential and the generation of action potential. Action potential is the change of the voltage of the membrane from a negative state to a positive value for a brief time. A process that is called depolarization and is accompanied by transmission of electrical impulses by the nerve cell. The changed membrane potential is as a result of the change (activation) of the membrane Na+, k + pump in response to stimuli. If the nerve cell is stimulated, the Na+, k + pump switches from its resting to activation state, causing much more sodium influx than potassium outflux. Consequently, producing a gradual depolarization of the membrane (generation of action potential). Action potential in the nerve cell lasts for few milliseconds, then returns so rapidly to its resting membrane potential. This is because sodium pump undergoes inactivation which would restore the membrane potential to its resting level . The action potential propagates or moves along the axon from the initial point to the terminal ending. The sodium ions influx at one point is considered as a stimulus for the next point (i.e. followed by movement of sodium ions into adjacent point). As a consequence the action potential (nerve impulse) propagates in direction from the soma to the axon terminal at constant speed. When the action potential reaches the end of the axon, it invades the synaptic terminal, causing the release of a chemical transmitter (neurotransmitter) used in the communication between neurons in a process called synaptic transmission. NOTE: After passage of the action potential, there is a brief period (the refractory period) during which the membrane can not be stimulated. This prevents the massage from being transmitted backward along the membrane. The Velocity of Action Potential : In unmyelinated nerve fiber the conduction velocity is proportional to the diameter of the axon. The larger diameter of the axon, the greater speed of propagation. This is because the axons with large diameter do not offer as much resistance to the flow of ions along the length of axon. In myelinated axon the velocity is greater and is determined not only by the diameter of the axon, but also by distance between nodes of Ranvier. The formation of myelin arround an axon prevents the penetration of ions needed for the conduction of the action potential, however there are nodes of Ranvier, where the membrane of the nerve axon is exposed and contains large number of sodium and potassium channels. In the nodes of Ranvier the membrane is depolarized and action potentials are generated. The generation of an action potential in a node of Ranvier causes the membrane in the adjacent node of Ranvier to depolarize and also to generate an action potential. In this way, the propagation of an action potential along a myelinated nerve axon appears to jump (saltus in latin) from one node of Ranvier to the next in the process of saltatory conduction. Thus, the greater distance between nodes of Ranvier, the greater the volecity of action potential propagation (figure 9). Figure 9: In a myelinated axon, the impulse jumps from one node of Ranvier to the next (saltatory conduction). SYNAPSES: The communication between nerve cells occurs at junctions called synapses. In the nervous system, there are two types of synapses (according to presence of chemical transmitter), (1)chemical synapses and (2)electrical synapses. 1-Chemical synapses mediate communication between distant cells: In the nervous system, the predominant type of synapse is the chemical synapse (figure 10). In chemical synapses, at least two cells participate–the cell producing the nerve impulse, called the presynaptic cell, and the target cell receiving the impulse, called the postsynaptic cell. The presynaptic component of the synapse consists of the terminal ending which contains vesicles called synaptic vesicles. These vesicles filled with chemicals referred to as neurotransmitters. When an action potential in the presynaptic neuron reaches the end of the axon, it causes the release of the neurotransmitter into the synaptic cleft. The transmitters bind to receptors located in postsynaptic cell membranes. This results in depolarization of its plasma membrane, causing transmission of action potential along the postsynaptic neuron. Figure 10: The structure of the chemical synapse 2-Electrical synapses mediate communication between adjacent cells: Is a gap junction (with no synaptic vesicles) in which impulses are conducted directly from one cell to another adjacent cell. Its conduction is faster than the chemical synapse. Electrical synapses are also found in cardiac cells of the heart, smooth muscle cells, and other cells that display a synchronization of activity. I- BASIC ORGANIZATION AND FUNCTIONS OF THE CENTRAL NERVOUS SYSTEM The central nervous system (CNS) is composed of the brain and spinal cord . The CNS is surrounded by bony skull and vertebrae. Both the spinal cord and brain consist of a white matter (bundles of axons each with a sheath of myelin) and grey matter (masses of cell bodies and dendrites). In the spinal cord, the white matter is at the surface and the grey matter inside. In the lower vertebrates (like fish and amphibians), they have their white matter on the outside of their brain as well as their spinal crod. However, in the brain of mammals this pattern is reversed. Both the brain and spinal cord are envloped by three membranes called the meninges (figure 11) which support and protect the central nervous system. They are : 1- Dura mater: The outer membrane, next to the interior surface of the skull and bony vertebrae. 2- Arachnoid : The middle membrane. 3- Pia mater: The inner membrane, covering the entire surface of the brain and spinal cord. Figure 11: Diagram showing the meninges surrounding the brain and spinal cord. The space between the arachnoid and pia mater (subarachnoid space) is filled with fluid called cerebrospinal fluid (CSF). The rest of the CSF lies in the ventricles of the brain. CEREBROSPINAL FLUID (CSF): The CSF is a clear colourless fluid secreted from the choroid plexus (network of blood capillaries) which is found in the lining of the ventricles of the brain. The CSF has a composition identical to that of the nervous system extracellular fluid (ECF) but differs from that serving as the ECF of the cells in the rest of the body. This compositional difference of CSF is maintained by the blood brain barrier (BBB), which is a system of tight junctions between endothelial cells of the nervous system blood capillaries. The CSF circulates from the interconnected ventricular system into the central canal of the spinal cord (figure 12). It flows through three foramena (apertures) at the fourth ventricle into the subarachnoid space along the brain and spinal cord, where it is directly absorbed into the cerebral veins to enter the blood stream. Normally, the total volume of CSF is about 150 ml and its daily rate of secretion equals its rate of absorption. If the flow of CSF is obstructed, CSF accumulates, causing hydrocephalus. In sever cases, the elevation of CSF in ventricles leads to compression of the brain blood vessels, which may lead to inadequate blood flow to the neurons, neuronal damage and mental retardation. Functions: (1) It acts as bath around brain and spinal cord to protect them from injury with position or movement. (2) It serves to transport nutrients into the nervous system and to remove harmful metabolilies from nervous system into blood. (3) It keeps constant intracranial pressure, if the volume of the brain increases, CSF drains away and if the brain shrinks, more fluid is retained. Figure 12: Diagram illustrating the location of the cerebrospinal in the ventricles and the spinal canal. 1- THE BRAIN During development , the central nervous system is formed from a long tube of ectoderm (neural tube). The anterior end of the tube becomes the brain. The lumen of which becomes dilated and produces a large ventricular system within the brain (4 ventricles), while the lumen of the caudal end of the tube (spinal cord) remains very small and is recognized in the adults as the central canal. In human, the brain weighs 350- 400 g at birth. As a child grows, the number of cells remains stable, but cells grow in size and the number of connecting cells increases. So, brain reaches 1300-1400g in adult human and is differentiated into 3 main sections, they are: (1) Prosencephalon (forebrain): subsequently divided into the telencephalon (cerebrum) and diencephalon (thalamus & hypothalamus). (2) Mesencephalon (midbrain): develops without further subdivisions. (3) Rhombencephalon (hindbrain): subdivides into the metancephalon (pons & cerebellum) and myelencephalon (medulla oblongate). During continuing formation of the brain, four different regions become apparent . These regions are: 1-Cerebrum 2- Diencephalon 3- Cerebellum 4- Brainstem (consists of midbrain, pons and medulla oblongata) (figure 13). Figure 13: The Brain BRAIN VENTRICLES: The brain contains four interconnected cavities (ventricles), which are filled with circulating CSF. This fluid is secreted into the ventricles by the cells of the choroid plexus. These ventricles are, the first and second (lateral) ventricles being the largest and are found in each cerebral hemisphere. The third ventricle is a narrow cleft that lies between the right and left thalami. It connects the lateral ventricles by means of interventricular foramena (figure 12). The fourth ventricle is a flattened pyramidal cavity found between the cerebellum and medulla oblongata and is connected to the third ventricle by the cerebral aqueduct (also called aqueduct of midbrain). The fourth ventricle is connected also with the central canal of the spinal cord and it has three openings (two lateral & one medial) through which CSF flows into the subarachnoid space. THE MAIN STRUCTURES OF THE BRAIN I- CREBRUM : The cerebrum is the largest portion of the brain associated with the higher brain functions, such as thought and action. It is divided into left and right hemispheres being largely separated by a longitudinal division . However the two hemispheres are still connected by bundels of myelinated nerve fibers (corpus callosum) to permit transfer of information between them. The outer surface of each hemisphere: consists of grey matter that represents the cerebral cortex. The cortex in each hemisphere is about 4 mm thick. It consists mostly of cell bodies and processes having no myelin covering. The neurons in the cortex are arranged in several layers (six) one above the other. They are mostly pyramidal shaped cells with dendrites extensively arborized to reach cortical surface. Cerebral cortex is highly convoluted and this makes the brain more efficient because it increases the surface area of the brain and the number of neurons in it. The surface of the cortex in each hemisphere is marked by grooves called sulci (singular sulcus) including two main lateral sulci and the central sulcus. The sulci divide the cortex into four lobes visible from outside, frontal lobe in front of the central sulcus, parietal lobe (immediately behind the central sulcus), temporal lobe (below the lateral sulcus) and occipital lobe at the back of the brain. Hidden beneath these lobes of the cortex are the olfactory bulbs, which receive inputs from the olfactory nerves (figure 14). The deeper parts of the cerebral hemispheres: consist of white matter that is made up of myelinated nerve fibers (nerve tracts), which in turn overlies cell clusters (grey matter) collectively termed subcortical nuclei. The nerve tracts may run as: 1) Association fibers from one part to another at the same hemisphere. 2) As connecting fibers from one hemisphere to the other. 3) As efferent (descending) or afferent (ascending) fibers, which carry impulse from or to the brain. LOBES OF THE CEREBRAL CORTEX: 1- FRONTAL LOBE: Frontal lobe is associated with the primary motor cortex and is important in conducting three functions. (a) speech. (b) thoughts and make decisions. (c) initiation and control of voluntary movement. 2- PARIETAL LOBE : Is a sensory area (primary somatosensory cortex) associated with specialized area for taste sensation. Somatosensory cortex is responsible for receiving impulses from somatic receptors to give sensation about touch, pain, pressure, temperature and position of the body in the space. The specialized sense organs of body (eyes, ears and nose) have other functional areas on the cortex . 3- THE TEMPORAL LOBE : Is a sensory area that receives signals from auditory nerves and concerned with hearing, speech and memory. 4- OCCIPITAL LOBE : Is a sensory area that receives signals from optic nerves and concerned with many aspects of vision and reading ability. Figure 14: Lobes of the cerebral cortex. THE SUBCORTICAL NUCLEI (BASAL GANGLIA): The name “basal ganglia” is an exception to the generalization that ganglia are neuronal cell clusters that lie outside the central nervous system. They are group of large nuclei (grey matter) that lie deep within the cerebral hemispheres and connect with motor cortex and other brain areas. They are important for controlling voluntary movement through activation by the motor cortex. II- THE DIENCEPHALON: It is the second component of the forebrain which is divided into two major parts (figure 15): 1) The thalamus. 2) The hypothalamus. (1) THE THALAMUS: Is a collection of several large nuclei (separated by the third ventricle) into two thalami lie close together. Functionally, the thalamic region serves as a relay station for various sensory inputs (except olfaction) before arriving to the primary cortical areas responsible for sensation (sensory function). It is also important to relay motor signals coming from basal ganglia and cerebellum on their way to the motor areas of the cortex (motor function). (2) THE HYPOTHALAMUS: Is located at the base of the brain, just above the pituitary gland and below the thalamus. Hypothalamus is a tiny region that accounts for less than 1% percent of the brain weight. It contains different nuclei and pathways that form the center for controlling endocrine functions (neuroendocrine coordination) and play an important role in controlling behaviors having to do for preservation of the individual life. Functions: a- Control of endocrine functions: Its secretions control the activity of the pituitary gland which in turn regulates the action of other endocrine glands. This occurs through secretion of releasing factors and releasing- inhibiting factors which are carried by its blood portal system to the anterior pituitary and tigger it’s secretion of such hormones as, adrenocorticotropic hormone (ACTH), follicle-stimulating thyrotropic hormone hormone (TSH), (FSH), and luteinizing lactogenic hormone hormone (LH), (LTH). Hypothalamus is also responsible for production of the posterior pituitary hormones (antidiuretic hormone and oxytocin) and regulation of their release. b- Autonomic nervous control: Hypothalamus is considered the principal higher brain center for control of ANS. Generally, the anterior and medial portion of hypothalamus are associated with the parasympathetic system, while the sympathetic system is regulated by the posterior and lateral portions. C- Cardiovascular regulation: The hypothalamus produces regulating effects on the heart and blood vessels indirectly, by impulses relayed to the cardiovascular centers of medulla. d- Body temperature regulation: A number of temperature regulating centers is located in hypothalamus to keep the body temperature at 37 C˚. If there is excess heat, impulses from temperature centers in hypothalamus (through the autonomic system) cause dilation of the blood vessels in the skin, and if the body is colder than it should be, hypothalamic impulses cause constriction of the cutaneous blood vessels. e- Regulation of food intake: There are two separate centers for regulating food intake, a hunger center and satiety center. Stimulation of hunger center causes the animal to eat, while stimulation of the satiety center causes an animal to ignore food. The hunger center is stimulated by a fall of the level of glucose in the blood. The levels of blood amino acids and fatty acids also play a role, although less pronounced. f- Regulation of water balance: If there is an increase in osmotic pressure due to water lack, two separate mechanisms go into effect: (1) The antidiuretic hormone (ADH) is produced, traveled along the nerve fiber that link the hypothalamus with the posterior pituitary gland and is secreted from the latter into the blood to cause the kidney tubules to conserve water, and a more concentrated urine is excreted. (2) Thirst center produces feeling of thirst, which stimulates the action of drinking. g- Control of emotional behavior: A number of centers associated with emotional reponses (anger, fear, pain and pleasure) are found in the hypothalamus (both in animals and in human) for participation in the control of emotional behaviors. PINEAL BODY: The roof of diencephalon gives outgrowth termed pineal body (also known as pineal gland). It usually take the form of a small oval mass attached to the brain by a fine stalk (figure 15). Pineal gland is sensitive to changes in light, receiving its information about light from the eyes to secrete melatonin hormone. Melatonin secretion, therefore, undergoes a marked 24-h cycle, being high at night and low during the day and it seems to affect skin pigmentation in lower vertebrates and to play a role in regulating biological rhythms in higher vertebrates. Figure 15: Diagram showing various regions of the brain. LIMBIC SYSTEM : The portion of the forebrain mainly concerned with emotions is termed limbic system. It includes portions of the cortex, thalamus, hypothalamus, basal nuclei and areas deep within the cerebrum, connected together in an integrated system. FUNCTIONS : 1- The limbic system primarily concerned with initiation and regulation of emotions and emotional homeostasis. 2- The limbic system serves to support the somatic motor reactions evoked by the emotional state through acceleration of the heart rate, elevation of blood pressure, release of adrenaline and increase of blood flow to skeletal muscles. III- CEREBELLUM : The cerebellum (little brain in Latin) consists of two deeply convoluted hemispheres. Each composed of an outer layer of grey matter (the cerebellar cortex), surrounding a mass of white matter, which contains several deeper cell clusters (nuclei). The cerebellum is another non cortical (subcortical) area that involved in the control and integration of the body voluntary movements. FUNCTIONS: Cerebellum doesn't initiate voluntary movement, however it is an important center for coordinating movement and for controlling posture and balance. The cerebellum accompalish these functions by receiving information (neural inputs) from eyes, ears, skin, muscles, joints or viscera and from areas of brain involved in control of voluntary movement. IV- BRAINSTEM : The brainstem connects spinal cord to the rest of the brain. It consists of: 1- MIDBRAIN : The midbrain is the upper most portion of the brainstem. It consists mainly of two large bundles of nerve fibers (white matter) called the cerebral beduncles uniting the pons with the thalamic region of the cerebrum. Between the beduncles, there is a narrow duct known as cerebral aqueduct (aqueduct of midbrain) which connect the third ventricle with the fourth ventricle. FUNCTIONS : a) The beduncles serve to connect motor fibers from cerebrum to cerebellum and to the spinal cord, that gives rise to a motor pathway conveying impulses to the skeletal muscle (concerned with the voluntary movement). b) The midbrain contains also the neuron cell bodies (nuclei) giving rise to the cranial nerves III (oculomotor) and IV (trochlear). 2- THE PONS: Is about 2.5 cm in length. It contains a large bundles of fibers consisting of descending fibers to the spinal cord and fibers passing from the pons to the cerebellum. FUNCTIONS: a) The above mentioned pathways in the bones are a part of the system that coordinate muscular activity. b) The pons also contains the neuron cell bodies (nuclei) giving rise to the cranial nerves V(trigeminal), VI (abductor), VII (facial) and VIII (auditory). 3- MEDULLA OBLONGATA: Is the remaining portion of the brainstem, about 3 cm in length. It continues through the foramen magnum of the skull with the spinal cord. FUNCTIONS: a) The descending fibers of the pons cross over in the medulla and continue down the spinal cord as the fiber tracts involved in the voluntary movements. b) The medulla also contains the neuron cell bodies (nuclei) of cranial nerves IX (glossopharyngeal), X (vagus), XI (accessory) and XII (hypoglossal). In the medulla, some portions of the cranial nerve nuclei form the so called vital centers of the medulla. Lesions in the medulla are especially serious if they involve the vital centers. These centers include the following : • Cardiac Centers: They are cardioacceleratory and cardioinhibitory centers , receiving impulses that rise in receptors in several body areas and sending impulses to the heart to regulate its rate of beat. • Respiratory Centers: Inspiratory and expiratory centers form part of the system responsible for regulating respiratory activity. • Vasomotor centers: Vasodilator and vasoconstrictor centers deal with the diameter of muscular blood vessels and thereby control the blood pressure. All of these vital centers are integrated in their activity, so that they complement one another to achieve a desired end result. During exercise, for example, heart rate increases, vasocontraction increases, blood pressure, and breathing is stimulated to increase oxygen intake and carbon dioxide elimination. The medulla, also including portions of the medullary cranial nerve nuclei, that form non–vital centers for intergration of the acts of: •Swallowing •Vomiting • Sneezing • Coughing THE RETICULAR FORMATION: It is a series of nerve cells (nuclei) that constitute a reticular formation, located in the brainstem. FUNCTIONS: The nuclei of the reticular formation receive inputs from most of the sensory systems of the body (optic, olfactory & auditory systems). It acts as a filter to incoming stimuli and determines important from unimportant before arriving to higher brain centers. For example, you may be unaware of conversation in a crowded situation, but the system alerts you when you hear your name. Stimulation of the "formation fibers" that pass to the thalamus and then to cerebral cortex, causes activation and alertness of the cortex in general and aids in maintaining the conscious state or wakefulness. 2- THE SPINAL CORD The spinal cord lies within the bony vertebral column. It is a selender of soft tissue with variable length among different vertebrates. In human, it is divided into 31 segments arranged into five regions (figure 16): 1- Cervical region (8 segments). 2- Thoracic region (12 segments). 3- Lumber region (5 segments). 4- Sacral region (5 segments). 5- Coccygeal region (1 segment). A cross section of the spinal cord shows central butterfly shaped area composed of interneurons, the cell bodies and dendrites of efferent neurons, the entering fibers of afferent neurons and glial cells. It is called grey matter because there are more cell bodies than myelinated fibers. The grey matter is surrounded by white matter which consists of groups of myelinated axons of interneurons. These groups of axons called fiber tracts or pathways, run longitudinal through the cord. Some descending (efferent) to relay information from the brain to the spinal cord and others ascending (afferent) to transmit information to the brain. Pathways also transmit information between different levels of the spinal cord. Figure 16: Spinal cord segments. A short distance from the cord, the dorsal and ventral roots from the same level combine to form a spinal nerve, one on each side of the spinal cord (figure 17). The spinal nerves are 31 pairs. They are designated by the four vertebral levels from which they exit: cervical, thoracic, lumbar and sacral. Figure 17: Spinal nerve. FUNCTIONS OF SPINAL CORD: 1- Spinal cord is responsible for all immediate reflexes in which brain is not involved. 2- Spinal cord is the main path way connecting the brain and peripheral nerveous system. 3- Conducts information to and from the brain. CROSSING OVER OF THE SPINAL TRACTS: Impulses reaching the spinal cord (ascending) from one side of the body eventually pass over to tracts running up to the other side of the brain and vice versa. In some cases this crossing over occurs as soon as the impulses enter the cord. In other cases, it doesn't take place until the tracts enter the brain it self. Figure 18: crossing over of the ascending (a&b) and descending (c) spinal tracts. II-PERIPHERAL NERVOUS SYSTEM The peripheral nervous system (PNS) provides a communication between the CNS and other tissues. Anatomically it is composed of 12 pairs of cranial nerves and 31 pairs of spinal nerves. I- Cranial Nerves (12 pairs): These are connected to the brain and composed of: 1- Nerves attached to cereberum: a) Olfactory nerve (I). b) Optic nerve (II). 2- Nerves attached to midbrain: a) Occulomotor nerve (III). b) Trochlear nerve (IV). 3- Nerves attached to pons: a) Trigeminal nerve (V). b) Adbucent nerve (VI). c) Facial nerve (VII). d) Auditory nerve (VIII). 4- Nerves attached to medulla oblongata: a) Glossopharyngeal nerve (IX). b) Vagus nerve (X). c) Accessory nerve (XI). d) Hypoglossal nerve (XII). Note that cranial nerves may be: • Purely sensory: I, II, VIII. • Purely motor: III, IV, VI, XI, XII. • Mixed (sensory and motor): the remaining (table 1). Table 1: The cranial nerves and information they transmit. Name Fibers I. Olfactory Sensory Carries inputs from receptors in olfactory epithelium. II. Optic Sensory Carries inputs from receptors in eye III. Oculo- Comments Motor Innervates skeletal muscles that move eyeball. IV. Trochlear Motor Innervates skeletal muscles that move eyeball V. Trigeminal Sensory motor (mixed) VI. Abducens VII. Facial Transmits information from receptors in skin of head Motor Innervates muscles of Jaw. Motor Innervates skeletal muscles that move eyeball. Sensory (mixed) Motor Transmits information from taste buds in tongue and mouth. Innervates skeletal muscles of face. VIII. Auditory Sensory Transmits information from receptors in ear. IX. Glossopharyngeal Sensory Transmits information from taste buds at tongue. (mixed) Motor Innervates skeletal muscles involved in swallowing and salivary glands. Sensory Transmits information from receptors in thorax and abdomen Motor Innervates skeletal muscles of thorax and abdomen. XI. Accessory Motor Innervates neck skeletal muscles. XII. Hypo- Motor Innervates skeletal muscles of tongue. X. Vagus (mixed) glossal In summary: all cranial nerves are involved with the head and neck regions, but the vagus nerve manages the internal organs. II- Spinal Nerves: (31 pairs): • These are attached to the sides of the spinal cord. • Each spinal nerve arises by two roots, dorsal and ventral (figure 17). • They are designated by the four vertebral levels from which they arise: cervical, thoracic, lumber and sacral (figure 16). For The Spinal Nerves: • Eight cervical nerves control the neck, shoulders, arms and hands. • Twelve thoracic nerves are associated with the chest and abdominal walls. • Five lumber nerves are associated with the hip and legs. • Five sacral nerves are associated with the genital and lower digestive tract. • A single pair of coccygeal nerve brings the total 31 pairs. As noted earlier, the spinal nerves contain nerve fibers that are the axons of both efferent and afferent neurons (mixed nerves). Afferent neurons carry information from sensory receptors to the CNS. The long part of their axon is outside CNS and is part of the PNS. While, efferent neurons carry signals out from the CNS to muscles or glands. This efferent division of PNS is more complicated than afferent being and is subdivided into: (1)Somatic division (voluntary). (2)Autonomic division (involuntary) (figure 19). The simplest distinction between somatic and autonomic divisions is that: • Neurons of somatic division innervate mainly skeletal muscles. • The autonomic neurons innervate smooth and cardiac muscles, glands and the gastrointestinal tract (GT) (internal organs). Figure 19: Divisions of nervous system . AUTONOMIC (INVOLUNTARY OR VISCERAL) NERVOUS SYSTEM The nervous system is functionally divided into: (1) somatic nervous system which controls organs under voluntary control (mainly muscles) and (2) the autonomic nervous system (ANS) which regulates functions of individual visceral systems, that are not under direct voluntary control (table 2). The ANS is predominantly an efferent system transmitting impulses from the (CNS) to peripheral organ systems. Its effects include control of heart rate and force of contraction, constriction and dilation of blood vessels, contraction and relaxation of smooth muscles in various organs, and secretions from exocrine and endocrine glands. Autonomic nerves constitute all of the efferent fibers which leave the CNS, except for those which innervate skeletal muscles. The ANS includes also some afferent fibers which are concerned with transmission of visceral sensation to CNS. These afferent fibers are usually carried to the CNS by major autonomic nerves, including the vagus, splanchnic or pelvic nerves. The ANS is divided into two separate divisions called the sympathetic and parasympathetic systems, on the basis of anatomical and functional differences. Both of these systems consist of myelinated preganglionic fibres which make synaptic connections with unmyelinated postganglionic fibres, which then innervate the effector organ (table 2). These synapses usually occur in clusters called autonomic ganglia. Most organs are innervated by fibers from both divisions of the ANS, and the influence is usually opposing. Table (2): Comparison between Somatic and Autonomic Nervous System. Feature Somatic Nervous Autonomic Nervous System System 1- Control Voluntary functions Involuntary functions. 2- Afferent Carry cutaneous sensation Carry visceral sensations. (sensory) fibers 3- Center In the brain and anterior In the brain and lateral horn horn in the spinal cord. in the spinal cord. 4-Efferent -One neuron. -Double neurons. (motor) fibers -No ganglia (i.e. no synapse -Presence of ganglia (i.e. synapse outside CNS). outside CNS). -Thick myelinated nerve -Preganglionic is thin myelinated nerve fibers and fibers. postganglionic is non myelinated nerve fibers. -Fast conducting. -Leads only to exitation (contration). -Slowly conducting. muscle -Either excitatory or inhibitory to effector organs. 5- Effector Mainly skeletal muscles. organs Smooth muscles, cardiac muscles and glands. 6- Chemical Acetylcholine. transmitter At preganglionic nerve endings: acetylcholine and at postganlionic endings: nerve acetylcholine norepinephrine. Parasympathetic Nervous System: The preganglionic outflow of the parasympathetic nervous system arises from the cell bodies of the motor nuclei of the cranial nerves III, VII, IX and X in the brain stem and from the second, third and fourth sacral segments of the spinal cord. It is therefore also known as the cranio-sacral outflow (figure 20). Preganglionic fibres run long distant to the effector organ and synapse in ganglia close to or within that organ, giving rise to postganglionic fibres which then innervate the effector organ. The chemical transmitter at both pre and postganglionic synapses in the parasympathetic system is acetylcholine. Functions: The parasympathetic system is dominant when the individual is relaxed and non threatened (normal situations). It is concerned with preservations energy in the body, as it causes a reduction in heart rate and blood pressure, and facilitates digestion and absorption of nutrients, and consequently the excretion of waste products. or Figure 20: Parasympathetic nervous system. Sympathetic Nervous System: The cell bodies of the sympathetic preganglionic fibres are in the lateral horns of the spinal cord in the thoracic and in the frist and second lumbar segments (T1-L2), so called thoraco-lumbar outflow (finger 21). The preganglionic fibres travel a short distance in the mixed spinal nerve, and then branch off to enter the sympathetic ganglia, which lie close to the spinal cord and from two chains of ganglia extending from the cervical to the sacral region. They are called the sympathetic chains (trunks). The short preganglionic fibres which enter the chain make a synapse with a postsynaptic fiber either at the same level, or at a higher or lower level, and then the postganglionic fibers extend long distance to innervate the effector organ. Figure 21: Sympathetic nervous system. In the sympathetic system, some preganglianic fibres do not synapse in the sympathetic chains but terminate in separate ganglia, called collatral ganglia (the celiac, superior mesenteric & inferior mesenteric ganglia) located in the abdominal cavity close to the innervated organ (figure 22). The neurotransmitter at the perganglionic synapse is acetylcholine, while norepinephrine is the neurotransmitter in the postsynaptic endings. Functions: In contrast to the parasympathetic system, the sympathetic system enables the body to be prepared for fear, flight or fight (emergency situations). Sympathetic stimulation causes an increase in heart rate, blood pressure and cardiac output, a diversion of blood flow from the skin and splanchnic vessels to those supplying skeletal muscle, increased pupil size, broncho-dilation, contraction of GIT sphincters. Sympathetic activity also increases energy expenditure of the body by increasing mobilization of glucose from glycogen and inhibition of insulin secretion from pancreas. Figure 22: Course of sympathetic fibers. Adrenal Medulla: The adrenal medulla is a modified sympathetic ganglion, whose cell bodies do not send out post ganglionic axons, but instead, upon activation by preganglionic axons release their transmitters into the blood stream (figure 23). This “ganglion”, called the adrenal medulla, therefore functions as an endocrine gland whose secretion is controlled by sympathetic preganglionic nerve fibers. It releases a mixture of about 80% adrenaline (epinephrine) and 20 % noradrenaline (norepinephrine) into the blood (plus small amounts of other substances including dopamine. These catecholamines, called homones rather than neurotransmitters. Figure 23: Transmitters used in the various components of the autonomic nervous system. They are: Ach, acetylcholine; NE, norepinephrine; E, epinephrine. The Physiologic Actions Of Sympathetic And Parasympathetic Systems. The action of the sympathetic and parasympathetic inputs to an organ generally have opposite effects, however, actions may be parallel (table 3). These actions operate to control visceral functions. For instance, when the blood pressure becomes too high, the parasympathetic inputs are activated to decrease the heart rate, by releasing acetylcholine. When acetylcholine binds to receptors located on pacemaker cells (which are cardiac cells that regulate heat rate), this slows their pacemaker activity, decreases the heart rate, and ultimately decreases the blood pressure. When the blood pressure is too low, the sympathetic inputs to the heart release norepinephrine. The binding of norepinephrine to receptors on cardiac cells resulting in an increase in heart rate. Table 3: Actions of sympathetic and parasympathetic divisions. (I)Antagonistic action: Sympathetic Parasympathetic 1- Pupil Dilation Constriction 2- Air passages. Dilatation Constriction 3- Heart 4- GIT: Wall rate of contraction Relaxation & secretory activity. rate of contraction Contraction & secretory activity. 5- Rectum Retention of faeces Defecation 6-Urinary bladder Retention of urine Micturition 7- Blood vessels Vasoconstriction Vasodilatation Little and viscid Large and watery salivary secretion (II) Parallel action: Salivary secretion salivary secretion In summary: (1) whole sympathetic actions tend to go off together, while parasympathetic actions do not go off together. (2) stimulation of sympathetic actions is useful, while parasympathetic stimulation is fatal