Meeting 2 Nervous System PDF

The Nervous System Neurotransmitter & Sensory System By: Rahmad Abdillah Objective After studying this chapter, you should be able to: Recognize the major distribution of the various types of receptors that mediate the functional response...

The Nervous System Neurotransmitter & Sensory System By: Rahmad Abdillah Objective After studying this chapter, you should be able to: Recognize the major distribution of the various types of receptors that mediate the functional responses of the common neurotransmitters: amino acids (glutamate and GABA), acetylcholine, monoamines (norepinephrine, epinephrine, dopamine, and serotonin), and opioid peptides. List receptor antagonists for each of the common neurotransmitters. Describe the location, type, and function of receptors that mediate the sensations of touch, temperature, and pain. Describe the steps involved in sensory transduction and action potential generation in cutaneous mechanoreceptors and nociceptors. Explain the basic elements of sensory coding including modality, location, intensity, and duration and how these properties relate to receptor specificity, receptive field, receptor sensitivity, and receptor adaptation. Describe the deficits caused by lesions of ascending sensory pathways that mediate touch, pain, and temperature. The Autonomic Nervous System  The autonomic nervous system (ANS) is actually part of the peripheral nervous system in that it consists of motor portions of some cranial and spinal nerves.  The ANS has two divisions: sympathetic and parasympathetic. Often, they function in opposition to each other.  An autonomic pathway, however, is a two-neuron pathway, it consists of two motor neurons that synapse in a ganglion outside the CNS.  The first neuron is called the preganglionic neuron, from the CNS to the ganglion. The second neuron is called the postganglionic neuron, from the ganglion to the visceral effector. The Sympathetic Division Another name for the sympathetic division is thoracolumbar division, which tells us where the sympathetic preganglionic neurons originate, their cell bodies are in the thoracic segments and some of the lumbar segments of the spinal cord. Their axons extend to the sympathetic ganglia, most of which are located in two chains just outside the spinal column. This anatomic arrangement has physiological importance: The sympathetic division brings about rapid and widespread responses in many organs. The sympathetic division is dominant in stressful situations, which include anger, fear, or anxiety, as well as exercise. For our prehistoric ancestors, stressful situations often involved the need for intense physical activity—the “fight-or-flight response” The Parasympathetic Division The other name for the parasympathetic division is the craniosacral division. The cell bodies of parasympathetic preganglionic neurons are in the brainstem and the sacral segments of the spinal cord. The parasympathetic division dominates in relaxed (non-stress) situations to promote normal functioning of several organ systems. Digestion will be efficient, with increased secretions and peristalsis; defecation and urination may occur; and the heart will beat at a normal resting rate. The Autonomic Nervous System The Autonomic Nervous System Neurotransmitters  Neurotransmitters are chemical messengers that transmit signals from a neuron to a target cell across a synapse.  Target cell may be a neuron or some other kind of cell like a muscle or gland cell.  Neurotransmitters are packaged into synaptic vesicles - presynaptic side of a synapse Vesicles (containing neurotransmitters) Synaptic cleft Receptors Receiving neuron Properties Of Neurotransmitters 1) Synthesized in the presynaptic neuron 2) Localized to vesicles in the presynaptic neuron 3) Released from the presynaptic neuron under physiological condition 4) Rapidly removed from the synaptic cleft by uptake or degradation 5) Presence of receptor on the post-synaptic neuron. 6) Binding to the receptor elicits a biological response  Chemistry of Transmitters Many neurotransmitters and the enzymes involved in their synthesis and catabolism are localized in nerve endings. There are three main classes of chemical substances that serve as neurotransmitters and neuromodulators: 1. Small molecule transmitters (eg, glutamate, γ-aminobutyric acid [GABA], and glycine), acetylcholine, and monoamines (eg, norepinephrine, epinephrine, dopamine, and serotonin). 2. Large-molecule transmitters include neuropeptides such as substance P, enkephalin, and vasopressin. 3. Gas transmitters include nitric oxide (NO) and carbon monoxide (CO) Types of Neurotransmitters EXCITATORY INHIBITORY BOTH Glycine Acetylcholine Glutamate GABA Nor epinephrine Aspartate Serotonin Nitric oxide Dopamine Classes of CNS Transmitters  ACETYLCHOLINE (ACh)  Acetylcholine was the first neurotransmitter to be discovered.  Isolated in 1921 by a German biologist named Otto Loewi.  Uses choline as a precursor - cholinergic neurotransmitter. Acetylcholine is the transmitter at the neuromuscular junction, in autonomic ganglia, and in postganglionic parasympathetic nerve-target organ junctions and some postganglionic sympathetic nerve-target junctions.  Used by the Autonomic Nervous System, such as smooth muscles of the heart, as an inhibitory neurotransmitter.  Responsible for stimulation of muscles, including the muscles of the gastro- intestinal system.  Used everywhere in the brain.  Related to Alzheimer's Disease.  ACETYLCHOLINE (ACh) Acetylcholine is released when a nerve impulse triggers the influx of Ca2+ into the nerve terminal transported into the presynaptic nerve terminal by a Na+-dependent choline transporter (CHT), which can be blocked by the drug hemicholinium Acetylcholine must be rapidly removed from the synapse if repolarization is to occur. The removal occurs by way of hydrolysis of acetylcholine to choline and acetate, a reaction catalyzed by the enzyme acetylcholinesterase in the synaptic cleft. Biochemical events at a cholinergic synapse  Dopamine  Is synthesized in three steps from the amino acid tyrosine.  Associated with reward mechanisms in brain.  Generally involved in regulatory motor activity, in mood, motivation and attention.  Schizophrenics have too much dopamine.  Patients with Parkinson's Disease have too little dopamine.  Dopamine Dopamine is transported from the cytoplasm into the vesicle by the vesicular monoamine transporter (VMAT), which can be blocked by the drug reserpine. NE and other amines can also be carried by VMAT. Dopamine is converted to NE in the vesicle. Once dopamine is synthesized, it is transported into the vesicle by the VMAT. Norepinephrine (Adrenaline)  Synthesized directly from dopamine.  Direct precursor to epinepherine.  It is synthesized in four steps from tyrosine.  Synthesized within vesicles.  Norepinephrine is strongly associated with bringing our nervous systems into "high alert."  It increases our heart rate and our blood pressure. It is also important for forming memories. Glutamate The amino acid glutamate is the main excitatory neurotransmitter in the brain and spinal cord and may be responsible for 75% of the excitatory transmission in the CNS. There are two distinct pathways involved in the synthesis of glutamate 1. α-ketoglutarate produced by the Krebs cycle is converted to glutamate by the enzyme GABA transaminase (GABA-T) 2. Second pathway, glutamate is released from the nerve terminal into the synaptic cleft by Ca2+-dependent exocytosis and transported via a glutamate reuptake transporter into glia, where it is converted to glutamine by the enzyme glutamine synthetase  Glutamate (Glu) released into the synaptic cleft by Ca2+- dependent exocytosis. Released Glu can act on ionotropic and G- protein-coupled receptors on the postsynaptic neuron. In glia, Glu is converted to glutamine (Gln) by the enzyme glutamine synthetase; Gln then diffuses into the nerve terminal where it is hydrolyzed back to Glu by the enzyme glutaminase. In the nerve terminal, Glu is highly concentrated in synaptic vesicles by a vesicular glutamate transporter γ-AMINO BUTYRIC ACID (GABA)  Synthesized directly from glutamate.  GABA is the major inhibitory mediator in the brain and mediates both presynaptic and postsynaptic inhibition.  Present in high concentrations in the CNS, preventing the brain from becoming overexcited.  If GABA is lacking in certain parts of the brain, epilepsy results. Serotonin (5-HT) ▪ Synthesized in two steps from the amino acid tryptophan ▪ Regulates attention and other complex cognitive functions, such as sleep (dreaming), eating, mood, pain regulation. ▪ Too little serotonin has been shown to lead to depression anger control etc.  Serotonin is transported into the vesicles by the VMAT. After release from serotonergic neurons, serotonin is recaptured by the relatively selective serotonin transporter (SERT). Once serotonin is returned to the nerve terminal, it is either taken back into the vesicles or is inactivated by MAO to form 5- hydroxyindoleacetic acid (5-HIAA) Receptors The action of a chemical mediator on its target structure is more dependent on the type of receptor on which it acts than on the properties of the mediator. There are five ligands-receptors binding. 1. Each chemical mediator has the potential to act on many subtypes of receptors. For example, norepinephrine acts on α1-, α2-, β1-, β2-and β3-adrenergic receptors. This multiplies the possible effects of a given ligand and makes its effects in each cell more selective 2. Receptors for many neurotransmitters are located on both presynaptic and postsynaptic elements. A presynaptic receptor called an auto-receptor often inhibits further release of the transmitter, providing feedback control. Ex: norepinephrine acts on α2-presynaptic receptors to inhibit additional norepinephrine release. A presynaptic hetero-receptor is one whose ligand is a chemical other than the transmitter released by the nerve ending on which the receptor is located. For example, norepinephrine acts on a heteroreceptor on a cholinergic nerve terminal to inhibit the release of acetylcholine. In some cases, presynaptic receptors facilitate the release of neurotransmitters. Receptors 3. Receptors are grouped into two large families based on structure and function: ligand-gated channels (also known as ionotropic receptors) and metabotropic receptors (also known as G-protein-coupled receptors [GPCRs]). In the case of ionotropic receptors, a membrane channel is opened when a ligand binds to the receptor; and activation of the channel usually elicits a brief (few to tens of milliseconds) increase in ionic conductance. Thus, these receptors are important for fast synaptic transmission.  Receptors 4. Receptors are concentrated in clusters on the postsynaptic membrane close to the endings of neurons that secrete the neurotransmitters specific for them. This is generally due to the presence of specific binding proteins for them. Receptors 5. In response to prolonged exposure to their ligands, most receptors become unresponsive; that is, they undergo desensitization. This can be of two types: homologous desensitization, with loss of responsiveness only to the ligand and maintained responsiveness of the cell to other ligands; and heterologous desensitization, in which the cell becomes unresponsive to other ligands as well. Conclusion Steps In Neurotransmitter Processing Synthesis: Neurotransmitters are synthesized by the enzymatic transformation of precursors. Storage: They are packaged inside synaptic vesicles Release: They are released from presynaptic terminal byexocytosis when calcium enters axon terminal during an action potential diffuse across the synaptic cleft to the postsynaptic membrane Binding: They bind to receptor proteins. Inactivation: The neurotransmitter is degraded either by being broken down enzymatically, or reused by active reuptake. Conclusion Steps In Neurotransmitter Processing Synthesis: Neurotransmitters are synthesized by the enzymatic transformation of precursors. Storage: They are packaged inside synaptic vesicles Release: They are released from presynaptic terminal byexocytosis when calcium enters axon terminal during an action potential diffuse across the synaptic cleft to the postsynaptic membrane Binding: They bind to receptor proteins. Inactivation: The neurotransmitter is degraded either by being broken down enzymatically, or reused by active reuptake. The Integumentary System The Skin The two major layers of the skin are the outer epidermis and the inner dermis. “Each of these layers is made of different tissues and has very different functions”. EPIDERMIS The epidermis is made of stratified squamous keratinizing epithelial tissue and thickest on the palms of the hands and the soles of the feet. The cells are called keratinocytes, and there are no capillaries present between them. The Skin The Integumentary System The Skin The Integumentary System DERMIS The dermis is made of an irregular type of fibrous connective tissue, irregular meaning that the fibers are not parallel but criss-cross and run in all directions. Fibro-blasts produce both collagen and elastin fibers. Recall that collagen fibers are strong, and elastin fibers are able to recoil after being stretched. Strength and elasticity are two characteristics of the dermis. With increasing age, the deterioration of the elastin fibers causes the skin to lose its elasticity. We can all look forward to at least a few wrinkles as we get older. Cutaneous Receptors Most sensory receptors for the cutaneous senses are found in the dermis. SENSORY RECEPTORS CUTANEOUS MECHANORECEPTORS Touch and pressure are sensed by four types of mechanoreceptors SENSORY RECEPTORS 4-Channel Model of Touch Perception MERKEL MEISSNER Sustained pressure; Perpendicular to surface; Spatial shape; Bump/hole discrimination Texture discrimination (Touch screens) RUFFINI PACINIAN Parallel to skin surface; Parallel to skin surface; Deep lateral stretch; Curvature; Rigidity; Grip stability/slippage Deep pressure (Fingerprints) Sensory Pathway 1. Receptors—detect changes (stimuli) and generate impulses. Once a specific stimulus has affected receptors, however, they all respond in the same way by generating electrical nerve impulses. All receptors change the energy of a stimulus to the electrical energy of a nerve impulse. 2. Sensory neurons—transmit impulses from receptors to the central nervous system. These sensory neurons are found in both spinal nerves and cranial nerves, but each carries impulses from only one type of receptor. 3. Sensory tracts—white matter in the spinal cord or brain that transmits the impulses to a specific part ofthe brain. 4. Sensory areas—most are in the cerebral cortex These areas feel and interpret the sensations. Learning to interpret nerve impulses as sensations begins in infancy (if not before birth), without our awareness of it, and continues throughout life. Characteristics of Sensations 1. Projection—the sensation seems to come from the area where the receptors were stimulated. If you touch this book, the sensation of touch seems to be in your hand but is actually being felt by your cerebral cortex. 2. Intensity—some sensations are felt more distinctly and to a greater degree than are others. When more receptors are stimulated, more impulses will arrive in the sensory area of the brain. The brain “counts” the impulses and projects a more intense sensation. 3. Contrast—the effect of a previous or simultaneous sensation on a current sensation, which may then be exaggerated or diminished. If, on a very hot day, you jump into a swimming pool, the water may feel quite cold at first. The brain compares the new sensation with the previous one, and since there is a significant difference between the two, the water will seem colder than it actually is. 4. Adaptation—becoming unaware of a continuing stimulus. Receptors detect changes, but if the stimulus continues, it may not be much of a change, and the receptors will generate fewer impulses. Nociceptors Mechanical nociceptors respond to strong pressure (eg, from a sharp object). Thermal nociceptors are activated by skin temperatures above 45°C or by severe cold (