Part One: The Major Structures of the Brain. The human brain is a mass of pinkish-gray tissue containing a neural network involving approximately 10 billion nerve cells, called neurons. Glial cells serve as the brain!!!s support system, in addition to blood vessels and secretory organs. Weighing in at a mere three pounds, the brain operates as the central control system for movement, sleep, hunger, and thirst. It controls nearly every vital activity necessary for survival. Emotions are controlled by the brain: anger, fear, joy, love, elation, contentment, and happiness find their origin inside the brain. Furthermore, the brain receives and interprets the multitude of signals being sent by other parts of the body and the outside environment. There are three major divisions of the brain: the forebrain, midbrain, and hindbrain. A. Forebrain: For anatomical study the forebrain is divided into two subdivisions: the telencephalon and the diencephalon. The primary structures of the telencephalon include the cerebral cortex, basal ganglia, and the limbic system. The diencephalon includes the thalamus and the hypothalamus. Telencephalon: Cerebral Cortex: Likened to the bark on a tree, the cerebral cortex surrounds the cerebral hemispheres. The cerebral cortex is the folded, convoluted tissue commonly imagined when an image/thought of the brain is recalled from memory. The folded, crumpled structure contains an enormous amount of small and large grooves (sulci and fissures) and bulges (gyri). This type of structure is beneficial for it greatly increases the overall surface are of the cortex. In fact, because of the convoluted design the area of the cerebral cortex is tripled! The cerebral cortex is commonly referred to as gray matter. This is based upon the appearance of the cortex which, due to the predominance of cells appears grayish brown. The neurons of the cerebral cortex are connected to other neurons within the brain via millions of axons located beneath the cortex. This area is white in color due to the concentration of myelin; it is often called white matter . One of the most apparent visible features of the brain is the division between the left and right hemispheres of the cerebral cortex. Through evolutionary advances the functions of each hemisphere have evolved. Mental and emotional differences between men and women are speculated to result from different modes of functioning between the two hemispheres. In most cases the left hemisphere is deemed the dominant half of the brain. This is due to its superior language abilities as well as its analytic, sequential. In general terms it is well understood that the left hemisphere controls linguistic consciousness, the right half of the body, talking, reading, writing, spelling, speech communication, verbal intelligence and memories, and information processing in the areas of math, typing, grammar, logic, analytic reasoning, and perception of details. The right hemisphere is associated with !!!unconscious!!! awareness (in the sense it is not linguistically based), perception of faces and patterns, comprehension of body language and social cues, creativity and insight, intuitive reasoning, visual-spatial processing, and holistic comprehension. Communication between the two hemispheres takes place through the corpus callosum, which, by the way, is more fully developed in women than men- likely giving rise to women!!!s intuition. The surface of the cerebral hemispheres is divided into four lobes corresponding to the names of the skull plates that protect them: the frontal lobe, parietal lobe, temporal lobe, and the occipital lobe. In addition to these four lobes, a fifth lobe exists called the insula. This lobe is internal and is not visible from the surface of the brain. The frontal lobes went through a tremendous evolutionary expansion 50,000 years ago. Subsequently, the capacities for long-term planning, goal development, and the ability to override immediate gratification in favor for future goals greatly expanded. The frontal lobes are sometimes associated with what it means to be human. Absence of the frontal lobes typically results in a person who is deemed emotionally shallow, listless, apathetic, and insensitive to social norms. According to Candace Pert, If God speaks to man, if man speaks to God, it would be through the frontal lobes, which is the part of the brain that has undergone the most recent evolutionary expansion. Furthermore, the frontal lobes exert a degree of control over the hypothalamus, which controls the autonomic nervous system and endocrine system, as well as organizes survival behavior. Control of movement is associated with the frontal lobes via the primary motor cortex located within this lobe. The parietal, temporal, and occipital lobes are specialized for perception. Within the parietal lobe is the primary somatosensory cortex which receives information pertaining to the senses of the body: touch, pressure, temperature, and pain. Visual information is received by the primary visual cortex located within the occipital lobe. Hearing is processed in the primary auditory cortex within the temporal lobe. The central sulcus (fissure of Rolando) divides the frontal lobe from the parietal lobe. The lateral fissure (fissure of Sylvius) separates the temporal lobe from the overlying frontal and parietal lobes. The parieto-occipital fissure separates the parietal and occipital lobes. The corpus callosum is the primary connection between the left and right hemispheres of the cerebral cortex. Connection between the two halves takes place through axons that unite geographically similar regions of the two cerebral cortices. Basal Ganglia: The basal ganglia are a collection of subcortical nuclei situated beneath the anterior portions of the lateral ventricles; they are involved with the control of movement. Parkinson!!!s disease has an effect upon the basal ganglia resulting in poor balance, rigidity of the limbs, tremors, weakness, and difficulty with initiating movements. Some anatomists consider the amygdala (primary component of the limbic system) a part of the basal ganglia given its location. The Limbic System: The limbic system is a collection of brain structures involved with emotion, motivation, multifaceted behavior, and memory storage and recall. The hippocampus (sea horse) and the amygdala (almond), along with portions of the hypothalamus, thalamus, caudate nuclei, and information]. septum function together to form the limbic system. Diencephalon: The diencephalon is the second major division of the forebrain. The principle structures include the thalamus and hypothalamus. Thalamus: The thalamus is the relay station for incoming sensory signals and outgoing motor signals passing to and from the cerebral cortex. With the exception of the olfactory sense, all sensory input to the brain connected to nerve cell clusters (nuclei) of the thalamus. The thalamus consists of two large connected lobes. The massa intermedia serves as a bridge connecting the two lobes of the thalamus. It is comprised of gray matter and is deemed a non-critical part of the brain; absence of which is outwardly unnoticeable. Hypothalamus: The hypothalamus is comprised of distinct areas and nuclei which control vital survival behaviors and activities; such as: eating, drinking, temperature regulation, sleep, emotional behavior, and sexual activity. It is located just beneath the thalamus and lies at the base of the brain. The autonomic nervous system and endocrine system are controlled by the hypothalamus. The anterior pituitary gland is directly connected to the hypothalamus via a special system of blood vessels. Neurosecretory cells released by the hypothalamus act upon the anterior pituitary gland which then secretes its hormones. Most hormones secreted by the anterior pituitary gland control other endocrine glands. Because of this the anterior pituitary gland is sometimes referred to as the Master Gland. Hormones of the posterior pituitary gland are also governed by the hypothalamus. B. Midbrain, The Mesencephalon: Two primary parts comprise the midbrain : the tectum and the tegmentum. Tectum: The primary structure of the tectum include the superior colliculi and the inferior colliculi. The superior colliculi form part of the visual system. The inferior colliculi are part of the auditory system. The structures appear as four small bumps located on the brain stem. Function in mammals relates to visual reflexes and reaction to moving stimuli. Tegmentum: The tegmentum is situated below the tectum. The reticular formation, periaqueductal gray matter, and the red nucleus and substantia nigra are part of the tegmentum. The reticular formation is comprised of more than 90 nuclei and an interconnected neural network located at the core of the brain stem. It receives sensory information and is involved with attention, sleep and arousal, muscle tonus, movement, and various vital reflexes. The periaqueductal gray matter consists of neural circuits that control sequences of movements constituting species-typical behavior. The red nucleus and substantia nigra are parts of the motor system. The red nucleus serves as one of two major fiber systems bringing motor information from the brain to the spinal cord. The substantia nigra affects the caudate nucleus via dopamine-secreting neurons. C. The Hindbrain: Metencephalon: Cerebellum (little brain): The cerebellum!!!s primary function involves control of bodily movements. It serves as a reflex center for the coordination and precise maintenance of equilibrium. Voluntary and involuntary bodily movements are controlled by the cerebellum. Visual, auditory, vestibular, and somatosensory information is received by the cerebellum, as is information on the movements of individual muscles. Processing of this information results in the cerebellum!!!s ability to guide bodily movements in a smooth and coordinated fashion. Pons: The pons appear as a large bulge in the brain stem between the mesencephalon and the medulla oblongata. The pons contain a portion of the reticular formation as well as nuclei believed important in the role of sleep and arousal. Myelencephalon: The myelencephalon is comprised of one structure: the medulla oblongata (oblong marrow). It is the origin of the reticular formation and consists of nuclei which control vital bodily functions. The medulla oblongata is the control center for cardiac, vasoconstrictor, and respiratory functions. Reflex activities, including vomiting, are controlled by this structure of the hindbrain. Appearing as a pyramid-shaped enlargement of the spinal cord, damage to this area typically results in immediate death. Part Two: The Neuron: A. Basic Neuron Description: A neuron, also known as a nerve cell, is the information processing and transmission device of the nervous system. They come in a variety of shapes, sizes, and types. In the human body, certain neurons reach up to three feet long. While differences exist between particular neurons given their specialization, most neurons are comprised of four primary structures: the soma; dendrites; axon; and terminal buttons. Soma: The soma is the cell body of the neuron. It houses the nucleus and the majority of cell components which sustain the life processes of the cell. The shape of the cell body varies greatly between the different types of neurons. Dendrites: The dendrites branch out from the soma resembling branches of a tree (dendron is Greek for Tree). With the exception of sensory neurons, the dendrites are the mechanism through which a neuron receives communication, incoming information, from other neurons. Sensory neurons transmit information where the incoming signal is generated by specialized receptors in the skin. Messages between two neurons are transmitted across the synapse, a junction between the receiving dendrites of one neuron and the information sending terminal buttons of another. Communication between neurons is a one-way affair. Signals are sent out by one neuron through the terminal buttons and received by the cell membranes of the receiving neuron. Axon: The axon is a long, slender tube that carries information away from the soma to the terminal buttons. Axons are usually covered by a myelinated sheath. The axon carries a basic message called termed an action potential. The action potential is a brief electrical/chemical event which starts at the end of the axon near the soma and travels downward to the terminal buttons. The action potential is consistent; I remains the same size and duration even through axonal branches. Each branch of an axon receives a full charge. As with the dendrites, axons come in different shapes. Furthermore, the three principal types of neurons are classified by the manner in which their axons and dendrites leave the soma. The most common type of neuron is the multipolar neuron which has one axon and many branches of dendrites. Bipolar neurons are depicted by having one axon and one dendritic tree, each located at opposite ends of the cell body. Bipolar neurons are typically sensory. They have a dendrite which receives information from a receptor which gets sent onto the central nervous system informing it of external events. Unipolar neurons, as found in the somatosensory system, consist of one stalk containing terminal buttons at one end and a dendritic tree at the other. Terminal Buttons: Most axons divide and split many times. At the ends of the branches there are small knobs which are called terminal buttons. The terminal buttons secrete neurotransmitters which affects the receiving cell. Neurotransmitters can be either excitatory or inhibitory. The nature of the neurotransmitter determines whether the receiving cell will send a message down its axon and communicate with the connected to its terminal buttons. A single neuron can receive information from hundreds of other neurons thus creating an intricate neural network. Additionally, the terminal buttons of a neuron can form synapses at the dendrites and/or cell body membranes of adjacent neurons. Internal Structure: The boundary of the nerve cell is defined by the cell membrane. Within the membrane are protein molecules which serve special functions for the cell. Some of the proteins detect substances outside the cell, such as the presence of hormones, and pass the information onto the interior of the cell. Other proteins serve as the cell!!!s gatekeeper, allowing some substances to pass into the cell while barring others. Some proteins functions as transporters carrying certain molecules into and out of the cell. At the center of the neuron is the nucleus which is round or oval and covered by a nuclear membrane. Inside are the nucleolus and chromosomes. The nucleolus manufactures small structures that are involved with protein synthesis, called ribosomes. Genetic information is contained on long strands of deoxyribonucleic acid (DNA) which make up the chromosomes. When portions of the chromosomes (genes) are active they cause the production of messenger ribonucleic acid (mRNA). Messenger RNA exits the nuclear membrane and attaches itself to ribosomes where the production of a specific protein takes place. Proteins provide structure and serve as enzymes, directing the chemical processes of a cell by controlling chemical reactions Cytoplasm makes up the bulk of the cell. It is a jellylike, semiliquid substance that fills the space within the membrane. Cytoplasm streams and flows, it is not static. Contained within it are small, specialized structures essential for the cell to perform its duties. The small structures include the: Mitochondria: This structures takes food and breaks it down into energy which the cell can use to carry out its job. Because it has its own DNA mitochondria are believed to have been their own organism which later merged inside of larger cells; a process and phenomenon known as symbiogenesis. Endoplasmic reticulum is a structure that serves as a storage reservoir and channel for transporting chemicals through the cytoplasm. Lipid molecules are also produced here. The Golgi apparatus assembles some complex molecules made up of simpler, individual molecules. It makes new synaptic vesicles out of the membranes of old vesicles which have served their purpose. In this sense the apparatus functions as the cell!!!s recycling center. The Golgi apparatus also operates as a packaging facility. It prepares and wraps proteins destined for export. Lysosomes are produced by the Golgi apparatus. They are small sacs which contain enzymes used to break down substances no longer needed by the cell. Lysosomes can cause cell death or suicide. The microtubule is the scaffolding of the cell. It is the skeleton of the cell and is involved with the transportation of substances from one place in a cell to another. Unlike most other types of cells found inside the body, neurons cannot be replaced when they die. All the neurons a person will have are present at birth; once a neuron is destroyed it can never be replaced. In addition, neurons possess a very high rate of metabolism requiring a constant supply of nutrients and oxygen. The needs of the neuron must be met by support cells in order for the neuron to survive. B. How the Neuron Works (electrically): Neurons have a negative electrical charge inside their cell membrane which makes them polarized. Polarization is caused by the free movement of positively charged potassium ions through the cell membrane, and the retention of large, negatively charged molecules within the cell. An active process keeps positively charged sodium ions outside the cell. Every cell has this difference in electrical charge, but when a stimulating current is applied to neuron, a unique event takes place. Stimulation of the neuron causes potassium ions to flow into the cell which reduces the negative charge; the process is called depolarization. At a certain moment, the membrane changes and the cell becomes permeable to sodium which quickly enters the cell causing a positive charge to occur within the neuron. This event is called the action potential. Once the action potential is reached at one area of the neuron, it moves down the axon via ion exchange at specific points called nodes of Ranvier. The size of the action potential is self limiting. A high internal concentration of sodium results in the pumping out of potassium followed by sodium ions. This restores the negative charge within the cell membrane causing the neuron to be repolarized. The entire process takes under 1/1000 of a second. The process can be repeated after the refractory period. The attainment of action potential results in the release of neurotransmitters at the terminal buttons. Thus, the electrical processes of a neuron constitutes inner-cellular communication. C. How the Neuron Works (chemically): When the internal electrical signal of the neuron reaches the tip of an axon, small presynaptic vesicles that contain neurotransmitters within the cell are stimulated. The neurotransmitters are then released into the synaptic cleft, a submicroscopic space between two neurons. The released neurotransmitters attach to specialized sites, receptors, on the surface of the adjacent neuron. Once a neurotransmitter is received by the receptors of a neuron the cell depolarizes and generates its own action potential. The stimulus of a neurotransmitter has a limited duration. The duration of a stimulus from a neurotransmitter is limited by two factors: the breakdown of chemicals in the synaptic cleft, and the reuptake by the neuron which sent the neurotransmitters. Neurons are now known to produce more than one type of neurotransmitter. In addition to neurotransmitters, two other types of transmitter substances are released by the terminal buttons of a neuron: neuromodulators and hormones. Neuromodulators are more dispersed and travel farther than neurotransmitters. They are released in larger amounts which allows them diffuse over a greater area of the brain, thus stimulating more neurons than do neurotransmitters. Hormones are released into the extracellular fluid and travel about the body through the bloodstream. Hormones can affect a neuron by stimulating receptors on either the surface of the cell membrane or deep inside their nuclei. Neurons containing the appropriate receptors are affected by the presence of the hormones. Affected neurons can alter behavior. Neurotransmitters, neuromodulators, and hormones affect nerve cells by attaching to a specific region of the receptor molecule called the binding site. This is the site at which neurosubstances and the receptors of nerve cells match one another; much like a lock and key. Whereas the neurosubstance functions as the key, the receptors act as a lock- their duty is to allow only the right kind of neurosubstance into the cell. Chemical that attach to a binding site are called ligands. In their natural form ligands are the neurotransmitters, neuromodulators, and hormones. However, other chemicals found outside the body can function the same way as the natural ligands. Artificial ligands include the substances of some plants and the venom of animals. Such ligands can also be manufactured in a laboratory. Pheromones can also function as artificial ligands. They are chemicals which enter the environment through sweat, urine, or the secretion of specialized glands. Their odor can be detected by receptors in the noses of other animals. When pheromones contact such receptors, they typically affect the reproductive behavior of other members of the same species. Pheromones are known to attract potential mates, cause sexual arousal, inhibit aggression, and alter the activity of the endocrine system. D. How the Synapse Operates (inhibitory/excitatory): Neurons communicate to each other by means of synapses; they release neurotransmitters which diffuse across the synapse. Synapses are formed where neurotransmitters diffuse across the gap between the terminal buttons of one neuron and the membranes of adjacent neurons. The transmitter substance can produce brief depolarizations or hyperpolarizations which are termed postsynaptic potentials. Postsynaptic potentials may either increase or decrease the firing of the axon in the postsynaptic neuron. The gap (synaptic cleft) between the terminal buttons of one neuron and the membrane of another is very small, normally measuring a mere 200 angstroms wide. The gap is filled with extracellular fluid through which the neurotransmitter diffuses. Synaptic vesicles are located in the cytoplasm of the terminal button, along with mitochondria and a Golgi apparatus. The vesicles are small rounded objects which generally come in two sizes: small and large. Small synaptic vesicles are found in all terminal buttons and contain molecules of the transmitter substance. They are produced in the terminal buttons by the Golgi apparatus. The Golgi apparatus operates as a recycling center. It makes new synaptic vesicles out of the membranes of old vesicles which have since released their substance into the synaptic cleft. Large synaptic vesicles are produced in the soma where they are subsequently transported down to the terminal buttons. The large vesicles contain one of a number of different neuropeptides. When an action potential reaches the terminal buttons, small synaptic vesicles located just inside the postsynaptic membrane attach themselves to the membrane and then break open; their contents are expelled into the synaptic cleft. The event takes only a few milliseconds. The way in which an action potential causes synaptic vesicles to release their transmitter substance is as follows: Some of the synaptic vesicles are docked against the presynaptic membrane where they are ready to release their contents into the synaptic cleft. Voltage-dependent calcium channels are located at the release zone of the presynaptic membrane. Depolarization by an action potential causes the calcium channels to open. At this moment, calcium ions flows into the cell propelled by electrostatic pressure and the force of diffusion. The entering calcium causes the fusion pore to open. While this is occurring the membrane of the synaptic vesicle fuses with the presynaptic membrane. This causes the vesicle to be pulled apart causing the release of the vesicle!!!s neurotransmitter into the synaptic cleft. After the synaptic vesicle has released its payload, the terminal button gains the vesicle!!!s membranes that have fused with it causing the terminal to become larger. In order for the terminal button membrane to maintain its optimum size and cease its expansion, the newly acquired vesicle membrane is received by the Golgi apparatus where it is recycled in the production of new synaptic vesicles. The new vesicles are packaged with molecules of transmitter substance and transported to the presynaptic membrane. The neurotransmitters released by the synaptic vesicles diffuse across the synaptic cleft and attach to the lock and key binding sites of special protein molecules attached to the postsynaptic membrane. When binding takes place, the postsynaptic receptors open up one or more neurotransmitter-dependent ion channels that permit the passage of specific ions into or out of the cell. Presence of transmitter substance in the synaptic cleft allows certain ions to pass through the membrane which the local membrane potential. The opening of ion channels by neurotransmitters can take place in one of two ways: direct or indirect. The direct method involves the presence of the appropriate transmitter molecular in the synaptic cleft, and a neurotransmitter-dependent ion channel equipped with its own binding site on the postsynaptic membrane. The postsynaptic receptor/ion channel is called an ionotropic receptor. When a molecule of neurotransmitter attaches to the binding site it causes the ion channel to open allowing sodium ions to enter the cell. The indirect method of opening ion channels is more common and involves a series of chemical events. Receptors involved with the indirect method are called metabotropic receptors for they require the cell to expend energy in opening the channels. One way in which ion channels are opened via the indirect method involves the binding of the transmitter substance with the receptor which then causes activates a G protein located nearby. The inactive G protein contains three subunits. When activated the alpha subunit breaks away from the other subunits and attaches to a special binding site of an ion channel. This causes the ion channel to open permitting ions to pass through the channel causing a postsynaptic potential. The second method mimics the first indirect method in the first two steps, but instead of the alpha subunit binding directly with an ion channel, it attaches to and activates an enzyme located in the membrane. The enzyme then causes the production of one of several different chemical in the cytoplasm of the cell. The newly produced chemicals, called second messengers, initiate another series of chemical steps that causes the ion channel to open resulting in a postsynaptic potential. Postsynaptic potentials can be either depolarizing, excitatory , or hyperpolarizing, inhibitory. Therefore, alterations in membrane permeability must be caused by the movement of particular types of ions. Within the postsynaptic membrane there are four types of neurotransmitter-dependent ion channels: sodium (Na+), potassium (K+), chloride (Cl-), and calcium (Ca2+
). The most important source of excitatory (depolarizing) postsynaptic potentials is the neurotransmitter-dependent sodium channel. Sodium is kept outside the cell by sodium-potassium transporters which wait for the forces of diffusion and electrostatic pressure to push it in. When sodium channels are opened depolarization occurs; an excitatory postsynaptic potential takes place. The sodium-potassium transporters also maintain a small surplus of potassium ions within the cell. When potassium channels are opened, some of these cations will leave the cell. The efflux of positively charged potassium ions hyperpolarizes the membrane generating an inhibitory postsynaptic potential. Inhibitory transmitter substances open chloride channels at many synapses rather than, or in addition to, potassium channels. The effect of opening chloride channels is dependent upon the membrane potential of the neuron. If in rest, nothing will happen because the forces of diffusion and electrostatic pressure are perfectly balanced for the chloride ion. But, if the membrane potential has already been depolarized by the activity of nearby excitatory synapses the opening of chloride channels will permit chloride to leave the cell bringing the membrane potential back to rest. Opening of chloride channels operate in neutralizing excitatory postsynaptic potentials. Calcium ions are positively charged ions located in high concentrations outside the cell. When calcium channels are opened the membrane is depolarized causing an excitatory postsynaptic potential. Certain enzymes are activated by the release of the calcium. They have a variety of effects; such as the production of biochemical and structural changes in the postsynaptic neuron. Part Three: The Major Neurotransmitters (mode of action/s): Although neurotransmitters have two types of effects, depolarization or hyperpolarization, many of them are not hard-wired. Many transmitters do not always have the same effect. The nature of the ion channels that are controlled by the postsynaptic can determine the effects of some transmitters. Transmitter substances are generally categorized into four groups: acetylcholine, monoamines, amino acids , and peptides. A. Acetylcholine (ACh): ACh is released at synapses on skeletal muscles and can also be found in the ganglia of the autonomic nervous system, as well as the target organs of the parasympathetic nervous system. Because the substance is located in convenient places, outside the central nervous system, it has been extensively studied by neuroscientists. On the membrane of skeletal muscle fibers ACh has an excitatory effect; it exhibits an inhibitory effect upon the membrane muscle fibers in the heart. This means that effect that a transmitter substance has is not determined by the chemical itself, but by the nature of the postsynaptic receptors it stimulates. Acetylcholine is found in the brain as well. There, it is involved with learning and recall, as well as in controlling the stage of sleep during which dreams occur. The substance is composed of choline and acetate; two substances which require internal bioengineering for use as ACh. ACh is deactivated by the enzyme acetylcholinesterase (AChE). This enzyme is present in the postsynaptic membrane and cytoplasm of the terminal buttons. Two types of ACh receptors exist, ionotropic and metabotropic. ACh ionotropic receptors are stimulated by nicotine and are referred to as nicotinic receptors. Such receptors are exclusively found in muscle fibers; smaller amounts of this receptor are found in the central nervous system. Metabotropic ACh receptors are stimulated by muscarine, a poison found in mushrooms, and are hence referred to as muscarinic receptors. These receptors are primarily found in the central nervous system. The reason that several types of receptors exist for the same neurotransmitter substance has to do with the receptor!!!s coupling to different kinds of ion channels, and to different G proteins which have different physiological effects. Ionotropic receptors produce rapid postsynaptic potentials; metabotropic receptors produce slower and longer potentials, and can also produce physiological processes within the cell to occur. Additionally, some receptors are sensitive to neuromodulators causing a single neurotransmitter to have a variety of effects in different locations of the nervous system. B. Monoamines: The monoamines include the four chemicals: epinephrine, norepinephrine, dopamine , and serotonin. The molecular structures of these chemicals are similar to each other causing some drugs to affect the activity of all of them at the same time. Epinephrine, norepinephrine, and dopamine belong to the subclass of monoamines called catecholamines. Serotonin belongs to the monoamines subclass called indolamines. Monoamines are produced by several systems of neurons within the brain. The majority of these systems consist of a small number of cell bodies located in the back of the brain. The axons of these cells branch repeatedly giving rise to an enormous number of terminal buttons widely distributed throughout the brain. Monoaminergic neurons serve to modulate the function of widespread regions throughout the brain. They serve as volume controls that increase or decrease the activities of particular brain functions. Dopamine (DA): Dopamine produces both excitatory and inhibitory postsynaptic potentials depending upon the receptor site. Dopamine has been discovered to perform various important functions associated with movement, attention, and learning. Tyrosine is the precursor molecule for both dopamine and norepinephrine. When tyrosine receives OH it becomes l-DOPA. The enzyme DOPA decarboxylase causes the l-DOPA to lose a carboxyl group causing it to become dopamine. When the enzyme beta-hydroxylase attaches a hydroxyl group to dopamine it creates norepinephrine. The enzyme monoamine oxidase (MAO) regulates the production of the catecholamines. MAO is found in the blood where it deactivates amines which could potentially cause dangerous increases in blood pressure. Parkinson!!!s disease is caused by the degeneration of dopaminergic neurons which serve to connect two parts of the brain!!!s motor system. This disease is characterized by tremors, rigidity of the limbs, poor balance, and difficulty in initiating movements. The cell bodies of these neurons are located in the brain!!!s substantia nigra. Those with Parkinson!!!s disease are given l-DOPA which serves to stimulate the production of dopamine. Consequently, a patient!!!s symptoms can be alleviated. Dopamine may also prove to have a connection with the mental disorder schizophrenia. The disorder involves hallucinations, delusions, and the disruption of normal, logical thought processes. Drugs which block activity of dopaminergic neurons reduce these symptoms causing researchers to speculate that schizophrenia is caused by overactivity of these neurons. Furthermore, patients with Parkinson!!!s disease being treated with l-DOPA occasionally display schizophrenic symptoms. There are at least five types of dopamine receptors, all of which are metabotropic. The two most important ones are the D1 and D2 dopamine receptors. The D1 receptors appear to be exclusively postsynaptic. Stimulation of these receptors increases the production of the second messenger cyclic AMP. D2 receptors are found both presynaptically and postsynaptically in the brain; stimulation of the D2 receptors casuses a decrease in AMP. Most of the neurons that release catecholamines do so through axonal varicosities, beadlike swellings of the axonal branches. The varicosities give the axonal branches the appearance of beaded chains. They form synapses with the base of the dendritic spines or the dendritic shaft. Epinephrine / Norepinephrine (NE): Like ACh, norepinephrine is also found in the autonomic nervous system and has been subjected to extensive research. The chemicals are also referred to as Adrenalin and noradrenalin. Epinephrine is a hormone that is produced by the adrenal medulla. It has also been discovered that epinephrine serves as a transmitter substance in the brain; yet it is not as important as norepinephrine. The transmitter substance is referred to as norepinephrine, whereas its adjectival form is noradrenergic. Noradrenergic neurons within the brain are involved with the control of alertness and wakefulness. Their synapses in the central nervous system produce inhibitory postsynaptic potentials. At the target organs of the sympathetic nervous system they typically have an excitatory effect. The transmitter is produced from dopamine with its final step of synthesis occurring inside synaptic vesicles. Once the vesicles are filled with dopamine, the dopamine is converted to norepinephrine through the action of dopamine beta-hydroxylase. Monoamine oxidase destroys excessive amounts of norepinephrine in the terminal buttons. Several types of noradrenergic receptors exist. The receptors are usually called adrenergic receptors for they are sensitive to epinephrine and norepinephrine. Neurons in the central nervous system contain both B1 and B2 adrenergic receptors and alpha1 and alpha2 adrenergic receptors. These four types of receptors are also found in various organs where they are responsible for the effects of the catecholamines when they function as hormones. All four receptors are also coupled to G proteins that generate AMP. Serotonin (5-HT): Serotonin produces inhibitory postsynaptic potentials at most synapses. Most of its behavioral effects are also inhibitory. 5-HT is known to play a role in the regulation of mood; the control of eating; the control of sleep and arousal; and in the regulation of pain. The serotonergic neurons are involved with the control of dreaming. LSD hallucinations appear to be caused by the drug interfering with the activity of serotonergic synapses which causes the user to dream while he/she is awake. The amino acid tryptophan is the precursor for serotonin. The enzyme tryptophan hydroxylase adds a hydroxyl group which produces 5-HTP. The enzyme 5-HTP decarboxylase removes a carboxyl group from 5-HTP resulting in 5-HT, serotonin. Seven types of serotonin receptors have been discovered. Of the seven 5-HT2
receptors are found exclusively in postsynaptic membranes. The other six have been found presynaptically and postsynaptically. With the exception of the 5-HT3
receptor, all serotonin receptors are metabotropic. C. Amino Acids: Glutamic Acid (glutamate): Glutamic acid and GABA produce postsynaptic potentials by activating postsynaptic receptors. Glutamic acid has direct excitatory effects on axons; GABA has inhibitory effects. The two substances serve to raise and lower the threshold of excitation which affects the rate at which action potentials occur. Glutamate is found throughout the brain where it appear to be the principal excitatory transmitter substance. MSG, as found in some Oriental food, contains the sodium salt of glutamic acid that can cause the mild neurological symptoms of dizziness and numbness in some people. Five types of Glutamic receptors have been found. Three are ionotropic, the other two metabotropic. The NMDA receptor has been linked to producing some of the synaptic changes responsible for learning. Gamma-aminobutyric Acid (GABA): GABA is produced from glutamic acid through action of the enzyme GAD which removes a carboxyl group. GABA is an inhibitory transmitter substance with widespread distribution throughout the brain and spinal cord. The GABAA
receptor is ionotropic and controls a chloride channel. The GABAB
receptor is metabotropic and controls a potassium channel. GABA-secreting neurons normally produce an inhibitory influence and are present in large numbers throughout the brain. Some research suggests that epilepsy is caused by an abnormality in the biochemistry of GABA-secreting neurons. GABAA
receptors contain binding sites for at least three transmitter substances and neuromodulators. The main site is for GAGA, whereas a second site binds with a class of tranquilizing drugs known as the benzodiazepines, which includes Valium and Librium. These drugs reduce anxiety, promote sleep, reduce seizure activity, and produce muscle relaxation. The third site binds to barbiturates and alcohol. Because GABA is an inhibitory neurotransmitter, the effects of benzodiazepines, barbiturates, and alcohol are the increase of neural inhibition. It is believed that the presence of these receptor sites implies that the brain produces neuromodulators that cause a stress reaction by either blocking or activating these receptors. Glycine: This amino acid is thought to be the inhibitory neurotransmitter in the spinal cord and lower portions of the brain. Although more research is needed to better understand glycine, it is known that the bacteria that cause tetanus release a chemical that blocks the activity of glycine synapses. The removal of the inhibitory effect of these synapses causes the muscles to contract continuously. D. Peptides: Peptides consist of two or more amino acids that are linked together by peptide bonds. They are synthesized by the ribosomes according to the instructions contained on the chromosomes of the nucleus. Neurons release several different peptides; most acting as neuromodulators, while some serve as neurotransmitters. The endogenous opioids comprise one of the most important families of peptides. These are the brain!!!s natural opiates which help to reduce pain. Three different types of opioid receptors have been detected. When opiate receptors are stimulated several different neural systems are activated. One system produces analgesia, another inhibits species-typical defensive responses, while another stimulates a system of neurons involved with internal reward/ reinforcement. Stimulation of the body!!!s internal reward system helps explain why opiates are abused. Released peptides are deactivated by enzymes and are not returned to the terminal buttons and recycled. The releasement of peptides is done in combination with one of the classical neurotransmitters. The reason for this is that peptides can regulate the sensitivity of presynaptic or postsynaptic receptors to the neurotransmitter. For example, the terminal buttons of the salivary nerve in a cat release both ACh and the peptide VIP. Only ACh is released while the axon fires at a low rate. This causes mild secretion of saliva. When the axon fires at a higher rate, both ACh and VIP are released. The additional presence of VIP causes a dramatic in increase in the sensitivity of the muscarinic receptors in the salivary gland to ACh which causes much more saliva to be released. Peptide hormones are also found in the brain where they serve as either neurotransmitters or neuromodulators. Sometimes the peripheral and the central peptide perform related functions. Example: Outside the nervous system the hormone angiotensin acts directly on the kidneys and blood vessels helping them cope with the loss of fluid, and inside the nervous system circuits of neurons that use angiotensin as a neurotransmitter perform similar functions. Part Four: The Limbic System (components + functions). In 1937 neuroanatomist Papez discovered a set of interconnected brain structures that formed a circuit which functioned as the brain!!!s center for motivation and emotion. The system appeared to consist of a set of interconnected structures surrounding the core of the forebrain. Parts of the limbic cortex, another form of the cerebral cortex located around the edge of the cerebral hemispheres, were also included in Papez!!!s system. The system was later expanded by Paul MacLean in 1949 to include additional structures; it became known as the limbic system in 1952. The limbic system is the seat of emotion, and is associated with learning and memory. In addition to regions of the limbic cortex, the primary structures of the limbic system are hippocampus and amygdala. The cingulate gyrus is also associated with the limbic system. Originally associated with emotion, it was later discovered that the hippocampal formation and the regions of the limbic cortex that surround it function in the processes of learning and memory. Today, it is clear that the limbic is directly involved with emotion, and plays a role in learning and memory. Early experiments on the limbic system demonstrated that specific limbic sites triggered emotion. Electrical stimulation of one region produced sudden anger, another rage, yet another, joy. However, while the site of emotion was discovered, the structures of the site were revealed not to be hard-wired. Stimulation of the amygdala would produce fear one day; elation the next. In time it was discovered that both the hippocampus and amygdala plays a role in memory. The hippocampus is known to consolidate and store memory, and the amygdala is believed to have perceptual and memory functions. In addition to coining the term limbic system, MacLean has also developed the triune brain theory. While studying the evolution of the limbic system, MacLean discovered that its evolutionary appearance is marked by the initial appearance of the cerebral cortex, and the development of emotional responses. The triune brain theory looks at the evolutionary stages of the brain and postulates that the human brain is actually three brains in one. The three brains of MacLean!!!s triune brain theory are: the reptilian brain, the mammalian brain, and the human brain. The reptilian brain includes the brain stem and its primary functions of keeping the organism alive. The mammalian brain resides in the limbic system. Its primary purpose is survival and preservation of self and species. Behavior of the mammalian brain is said to revolve around feeding, fighting, fleeing, and mating. For the mammalian brain there are no neutral emotions; all emotions are either agreeable or disagreeable. Through the mammalian brain mammals, including humans, feel pleasure when engaged in activities that enhance their preservation or the preservation of their species. Pain is experienced when survival needs are thwarted. From the limbic system!!!s perspective all experiences are judged in the dualistic fashion of pain or pleasure. The limbic brain scans for differences; typically when one is found it is deemed a threat to survival. The cerebral cortex comprises the human brain and is associated with advanced functions such as planning, thinking, analyzing, and communicating. The limbic brain can be seen as receiving its cues from the inside. Whereas the neocortex processes sensory information from the external world, the limbic system has, according to MacLean, a loose grip on reality. Temporal lobe epilepsy, resulting in limbic storms, produces the overwhelming feeling of experiencing truth. Without the reality check of the neocortex, the limbic system is capable of producing sensations of deja-vu, sudden memories, waking dreams, messages from God, even religious conversions. Cingulate Gyrus: MacLean states that the cingulate gyrus involves three distinct behaviors: nursing and maternal care, play, and audio-vocal communication. The three behaviors are exhibited my mammals which have a cingulate gyrus, and not by reptiles who lack a cingulate gyrus. The cortex covering the cingulate gyrus is an important part of the limbic system. Research indicates that it provides an interface between the decision-making processes of the frontal cortex, the emotional functions of the limbic system, and the brain mechanisms controlling movement. The cingulate gyrus communicates with the rest of the limbic system and other regions of the frontal cortex. Electrical stimulation of this part of the limbic system produces feelings that are either emotionally positive or negative. In general, the cingulate gyrus plays an excitatory role in emotions and motivated behavior. Hippocampus: The hippocampus is comprised of rows of 40 million nerve cells. If the hippocampus or pathways to it are damaged the ability to make new memories disappears; its function is to work on converting short-term memory into long-term memory. The hippocampus is considered important for localization memory. Interestingly, subtle clues into the physiological aspects of schizophrenia have been linked to the hippocampus. While still controversial, evidence has been found showing that the cells of the hippocampus which are normally arranged in an ordered manner, are grossly misaligned in the brains of schizophrenics. Such cells were seen to be rotated ninety degrees and some had their dendrites upside down. Cellular disarray of the hippocampus as seen in schizophrenics is believed to be genetic, or the consequence of a viral infection in the womb. The hippocampus in the right hemisphere of the brain is concerned with visual, emotional, tactile, and nonverbal memories. The hippocampus in the left hemisphere stores verbal and mathematical memories. Ultimately, the hippocampus stores in memories that are of emotional and motivational significance. Amygdala: The job of the amygdala is to discern the emotional significance of all aspects of experience. It adds color to thoughts and is responsible for the capacity to feel complex emotions like love and anxiety. The amygdala is extremely sensitive to tactile stimulation and is involved with memory. This limbic structure is interconnected with the hypothalamus, septal nucleus, and hippocampus. Visual and auditory perceptual information is received by the amygdala causing an emotional influence on our perception and thought. Damage to the amygdala can cause a person to misperceive or fail to perceive societal cues which are emotionally based. Traditionally, the amygdala has been linked to violent tendencies and behavior. This association dates back to 1968 when three prison inmates had parts of their amygdala burned out with electrodes to exorcise their violent nature. the basis for this was founded upon research that showed amygdalectomy being capable of taming vicious animals. Its success with the inmates was insignificant. Other Structures of the Limbic System: Hypothalamus: The hypothalamus controls and monitors hunger, thirst, and the ability to feel extreme pain or pleasure. Being the most primitive part of the limbic system, the hypothalamus it is the source from which all emotions originate as raw, powerful, undirected feelings. This structure represents the emotional core of our being. The hypothalamus is also closely involved with all aspects of sexual behavior: postures, ejaculation, and hormonal secretions relating to pregnancy and menstrual cycles. Differences between the hypothalamus of a man and woman indicate that the hypothalamus of females is more intricate and complex than males. Consideration of this fact yields insight on emotional gender differences. The hypothalamus is capable of exerting tremendous influence over the rest of the brain. Fortunately, it is normally controlled, in part, by the frontal lobes of the brain and the more recent limbic structures such as the amygdala. [also see hypothalamus discussed in question #1]. Septal Nuclei: This structure is involved with humankind!!!s ability to form emotional and social bonds with one another. The septal nuclei also exerts dampening effects on mood. By tapping into the emotional reservoir of the hypothalamus, the septal nuclei is able to exert emotional influence upon the rest of the brain. It is also interconnected with the hippocampus (thus likely to influence memory), and in some ways it serves to counteract the amygdala. Stimulation of the septum is known to generate strong feelings of pleasure. Part Five: The Autonomic Nervous System: Essentially, the nervous system is one system. However, it is divided into two primary parts based upon their different locations. The parts of the nervous system within the brain and spinal cord are considered the central nervous system. The parts of the nervous system extending outside the brain and spinal cord are classified together as the peripheral nervous system. With this distinction in mind, the peripheral nervous system serves as a network of nerves that allows the brain and spinal cord to interact and communicate with parts of the body existing outside the central nervous system. Further distinction results in a peripheral nervous system that is broken down into two primary parts: the somatic nervous system and the autonomic nervous system. The somatic nervous system involves the part of the peripheral nervous system which receives sensory information from the sense organs and controls movement of the skeletal muscles. The autonomic nervous system is involved with the self-governing (automatic) regulation of three aspects of the body: smooth muscle, cardiac muscle, and the glands. Smooth muscle is found in various places throughout the body and is regulated by the autonomic nervous system. It can be found in the skin where it enables hair to assist in bodily temperature regulation. Smooth muscle controls the eye!!!s pupil size and accommodates the lens. The gall bladder, urinary bladder, blood vessels, and walls and sphincters of the gut contain smooth muscle. The autonomic nervous system controls the actions of the glands. It controls the functions and involuntary muscles of the respiratory, circulatory, digestive, and urogenital systems. The autonomic nervous system regulates these parts of the body by sending impulses to them. The impulses are controlled by nerve centers in the lower part of the brain. Furthermore, the autonomic nervous system has a reciprocal effect on the internal secretions. The system is influenced by hormones to a certain degree, and it reciprocates this by influencing the rate of hormone production. In this respect the purpose of the autonomic nervous system involves the automatic regulation of vegetative processes in the body. Two antagonistic and anatomically separate systems comprise the autonomic nervous system. The two systems are called the sympathetic and parasympathetic divisions. With few exceptions, the two subdivisions influence and act upon the organs of the body; each system having a different effect. The Sympathetic Division: The sympathetic division of the autonomic nervous system stimulates the heart, dilates the bronchi, contracts the arteries, and inhibits the digestive system during moments of danger. This system serves to prepare the organism for fighting in order to help ensure survival in face of an environmental threat. The effect of the sympathetic division deals with the rapid accumulation and concentration of energy reserves stored in the body which can be utilized and directed toward ensuring survival. Rather than having energy being expended upon digestion while the immediate survivability of the organism is threatened, the sympathetic division harnesses such energy reserves in preparing the body for fight or flight. In addition to other physiological changes, when the sympathetic division is activated blood flow to the skeletal muscles is increased, the secretion of epinephrine is stimulated causing the heart rate and blood sugar level to rise, and piloerection occurs. The sympathetic division is widely distributed throughout the body. It arises from the middle portion of the spinal cord, joins the sympathetic ganglionated chain (sympathetic preventebral ganglia), and courses throughout the spinal nerves. This system of nerves connects the sympathetic division to the eyes, salivary gland, sweat glands and blood vessels in the skin, heart, lungs, stomach, kidneys and adrenals, pancreas, intestines, external genitalia, and bladder. Motor neurons of the sympathetic division are located in the gray matter of the thoracic and lumbar regions of the spinal cord. For this reason the sympathetic nervous system is also called the thoracicolumbar system. The fibers of these neurons exit the ventral roots and, once joined with the spinal nerves, branch off and pass into spinal sympathetic ganglia. Axons leaving the spinal cord through the ventral root form part of the preganglionic neurons. With the exception of the medulla adrenal, all sympathetic preganglionic axons enter the ganglia of the sympathetic chain, though not all of them synapse there. Some of the axons connect to other sympathetic ganglia located among the internal organs. Synaptic connection occurs in one of the ganglia. Postganglionic neurons are nerves which have formed a synapse with preganglionic axons inside one of the ganglia. These neurons send axons to one of the target organs of the sympathetic nervous system. Also under control of the sympathetic nervous system is the adrenal medulla, a cluster of cells located in the center of the adrenal gland. Closely resembling a sympathetic ganglion, the adrenal medulla is infused with preganglionic sympathetic neurons. The secretory cells of the adrenal medulla are similar to postganglionic sympathetic neurons. When stimulated the cells secrete epinephrine and norepinephrine which aid sympathetic functioning. The Parasympathetic Division: The parasympathetic nervous system arises above and below the sympathetic nervous system from the brain and from the lower part of the spinal cord. The parasympathetic division produces the opposite effect of the sympathetic division. Whereas the sympathetic division prepares the organism for optimum fight/flight functioning, the parasympathetic division prepares the organism for feeding, digestion, and rest. The parasympathetic division supports activities which assist in increasing the body!!!s supply of energy. Activities include: salvation, gastric and intestinal motility, secretion of digestive juices, and increased blood flow to the gastrointestinal system. Cell bodies giving rise to preganglionic axons in the parasympathetic division are found in two areas: the nuclei of some of the cranial nerves; and, the intermediate horn of the gray matter in the sacral region of the spine. Because of this the parasympathetic division is sometimes called the craniosacral system. Ganglia of the parasympathetic division are located close to the target organs. This makes postganglionic parasympathetic relatively short. The terminal buttons of both pre and postganglionic neurons in the parasympathetic division secrete acetylcholine. With the exception of the adrenal medulla, the parasympathetic division has connections with the same organs as the sympathetic nervous system. Part Six: The Reticular Formation (function and location): The reticular formation is composed of more than 90 nuclei located in the core of the medulla, pons, and midbrain; the three major of the brain stem. It has an intriguing netlike appearance (reticulum means little net) of diffuse neurons with complex dendritic and axonal processes. This network of cells, the reticular formation, is distributed along the length of a cerebrospinal fluid canal that runs longitudinally through the brain stem.