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Chapter 45: Organization of the Nervous System, Basic Functions of Synapses, and Neurotransmitters Guyton and Hall, Textbook of Medical Physiology, 12th edition General Design of the Nervous System • CNS Neuron: The Basic Functional Unit Fig. 45.1 General Design of the Nervous System • Sensory Part of the Nervous System- Sensory Receptors Fig. 45.2 Somatosensory axis of the nervous system General Design of the Nervous System • Sensory Part of the Nervous System- Sensory Receptors a. Information enters the CNS through peripheral nerves and is conducted immediately to sensory areas in 1. The spinal cord at all levels 2. The reticular substance of the medulla, pons, and mesencephalon 3. Cerebellum 4. Thalamus 5. Areas of the cerebral cortex General Design of the Nervous System • Motor Part of the Nervous System- Effectors- most important role of the nervous system is to control various bodily activities. This is achieved by controlling: a. Contraction of appropriate skeletal muscles b. Contraction of smooth muscles in internal organs c. Secretion of chemical substances by exocrine and endocrine glands General Design of the Nervous System • Skeletal Motor Axis Fig. 45.3 Skeletal motor nerve axis of the nervous system General Design of the Nervous System • Skeletal Motor Axis- skeletal muscles can be controlled from many levels of the CNS a. The spinal cord b. The reticular substance of the medulla, pons, and mesencephalon c. The basal ganglia d. Cerebellum e. Motor cortex General Design of the Nervous System • Processing of Information- “Integrative Function of the Nervous System a. Channeling and processing of information b. Approximately 99% of sensory information is filtered out and considered irrelevant and unimportant by the nervous system General Design of the Nervous System • Role of Synapses in Processing Information a. Some synapses transmit info from one neuron to another with ease, and others with difficulty b. Facilitatory and inhibitory signals from other areas of the nervous system can control synaptic transmission c. Synapses perform a selective action, often blocking weak signals and allowing strong signals to pass but sometimes select and amplify certain weak signals General Design of the Nervous System • Storage of Information (Memory) a. Information stored for future control of motor activities and for use in the thinking process is stored in the cerebral cortex b. Facilitation-each time a synapse transfer info, the synapses become more and more capable Major Levels of CNS Function • Spinal Cord Level a. A conduit for information to travel from the periphery of the body to the brain and vice versa b. Can cause walking movements c. Withdrawal reflexes d. Reflexes that stiffen the legs to support the body against gravity e. Reflexes that control local blood vessels, G.I. movements, and urinary excretion Major Levels of CNS Function • Lower Brain or Subcortical Level a. Control of most of the “subconscious” activities b. Arterial pressure and respiration c. Control of equilibrium d. Feeding reflexes e. Many emotional patterns (anger, excitement, sexual response, reaction to pain and pleasure) Major Levels of CNS Function • Higher Brain or Cortical Level a. Cerebral cortex is an extremely large memory storehouse b. Never functions alone but in association with lower centers of the nervous system c. Essential for most thought processes CNS Synapses • Types of Synapses a. Chemical 1. Almost all of the synapses in the CNS 2. First neuron secretes a neurotransmitter 3. Neurotransmitter binds to receptors on the second neuron (excites, inhibits, or modifies its sensitivity CNS Synapses (cont.) • Types of Synapses b. Electrical 1. Have direct open fluid channels that conduct electricity from one cell to the next 2. Have gap junctions which allow the movement of ions 3. Very few in the CNS but are the predominant type in the periphery of the body (i.e. skeletal muscle and smooth muscle contraction) CNS Synapses (cont.) • “One-Way Conduction at Chemical Synapses a. Always transmit signals in one direction (from the pre-synaptic neuron (releases neurotransmitter) to the post-synaptic neuron b. Called the principle of one-way conduction c. Allows signals to be directed toward specific goals CNS Synapses (cont.) • Physiologic Anatomy of the Synapse Fig. 45.5 Typical anterior motor neuron, showing pre-synaptic terminals on the neuronal soma and dendrites CNS Synapses (cont.) • Physiologic Anatomy of the Synapse a. Presynaptic terminals may be either stimulatory or inhibitory b. (Fig. 45.5) Neurons in other parts of the spinal cord and brain differ from the anterior motor neuron in: 1. 2. 3. 4. Size of the cell body Length, number, and size of the dendrites Length and size of the axon The number of presynaptic terminals CNS Synapses (cont.) • Presynaptic Terminals Fig. 45.6 Physiologic anatomy of the synapse CNS Synapses (cont.) • Neurotransmitter Release From the Presynaptic Terminal a. The membrane of the presynaptic terminal contains large numbers of voltage gated Ca channels b. When the membrane depolarizes, the channels open and Ca ions flow into the terminal c. Quantity of transmitter released is directly related to the amount of Ca that enters d. Ca binds with special proteins called release sites which open and allow the transmitter to diffuse into the synaptic cleft CNS Synapses (cont.) • Action of the Neurotransmitter a. The postsynaptic membrane contains receptor proteins that have two components: 1. A binding part that protrudes outward and binds the neurotransmitter, and 2. An ionophore part that passes through to the interior of the postsynaptic neuron 3. The ionophore is either an ion channel or a second messenger activator CNS Synapses (cont.) • Ion Channels- two types a. Cation- most often allow Na ions to pass, but sometimes K, and Ca also; lined with negative charges which attract cations but repel anions; opened by excitatory transmitters b. Anion- when channels are large enough, Cl ions pass through (cations are hydrated and too large); opened by inhibitory transmitters CNS Synapses (cont.) • Second Messenger Systems Fig. 45.7 Second messenger systems CNS Synapses (cont.) • Second Messenger Systems- the alpha component of the G protein performs one of four functions: a. Opening specific ion channels through the postsynaptic membrane b. Activation of cAMP or cGMP c. Activation of one or more cellular enzymes d. Activation of gene transcription CNS Synapses (cont.) • Excitatory Receptors in the Postsynaptic Membrane a. In excitation: the opening of Na channels to allow large numbers of + electrical charges to flow to the interior. This raises the membrane potential toward threshold (most widely used method of excitation) b. In excitation: depressed conduction through chloride or potassium channels or both; decreases the diffusion of Cl to the inside or K to the outside which makes the membrane potential more positive c. Metabolic changes to excite cell activity, increase excitatory receptors or decrease inhibitory receptors CNS Synapses (cont.) • Inhibitory Receptors in the Postsynaptic Membrane a. Opening of chloride channels allowing the rapid influx of ions which causes the membrane potential to become more negative, and therefore inhibitory b. Increase in conductance of potassium ions out of the neuron allowing positive ions to diffuse to the outside causing increased negativitiy, and therefore inhibitory c. Activation of receptor enzymes that inhibit metabolic functions or increase the number of inhibitory receptors or decrease the number of excitatory receptors Types of Neurotransmitters • Small Molecule, Rapidly Acting Transmitters Table 45.1 Class I Acetylcholine Class II: The Amines Class III: Amino Acids Norepinephrine GABA Epinephrine Glycine Dopamine Glutamate Serotonin Aspartate Histamine Class IV Nitric Oxide Types of Neurotransmitters • Neuropeptide, Slow Acting Transmitters or Growth Factors Hypothalamic Releasing Hormones Table 45.2 Pituitary Peptides Peptides-Act on Gut and Brain Peptides- Act on Gut and Brain From Other Tissues Thyrotropin RH ACTH Leucine enkephalin Insulin Angiotensin II Leutinizing HRH Betaendorphin Methionine enkephalin Glucagon Bradykinin Somatostatin Alpha-MSH Substance P Carnosine Prolactin Gastrin Sleep peptides LH CCK Calcitonin Thyrotropin VIP GH Nerve growth factor Vasopressin Brain derived neurotropic factor Oxytocin Neurotensin Electrical Events During Excitation • Resting Membrane Potential (-65 mV for a spinal motor neuron) Fig. 45.8 Electrical Events During Excitation • Concentration Difference of Ions Fig. 45.8 Electrical Events During Excitation • Uniform Distribution of Electrical Potential Inside the Soma • Effect of Synaptic Excitation on the Postsynaptic Membrane—Excitatory Postsynaptic Potential Electrical Events During Excitation Fig. 45.9 Three states of a neuron Electrical Events During Excitation • Generation of APs in the Initial Segment a. Axon hillock b. The membrane has 7x the voltage gated Na channels as does the membrane of the soma c. Threshold is about -45 mv (Fig. 45.9) Electrical Events During Inhibition • Effect of Inhibitory Synapses on the Postsynaptic Membrane—Inhibitory Postsynaptic Potential a. Inhibitory synapses open mostly Cl channels b. As the chloride ions enter, the membrane potential becomes more negative (toward -70 mV) c. Opening K channels allows the positive ions to move out; with the Cl, this causes a hyperpolarization d. Causes an IPSP (inhibitory postsynaptic potential) Electrical Events During Inhibition • Presynaptic Inhibition a. Release of an inhibitory substance onto the outside of the presynaptic nerve fibrils (usually GABA) b. Opens anion channels, allows Cl to diffuse inward c. Negative charges cancel much of the excitatory effect d. Occurs in many sensory pathways Electrical Events During Inhibition • Time Course of Postsynaptic Potentials Fig. 45.10 EPSPs Electrical Events During Inhibition • Spatial Summation- stimulation of many presynaptic terminals; the effects can summate until neuronal excitation occurs (Fig. 45.10) • Temporal Summation- successive discharges from a single presynaptic terminal; if they occur rapidly enough, they also summate Electrical Events During Inhibition • Simultaneous Summation of IPSPs and EPSPsthe two effects either completely or partially nullify each other • Facilitation of Neurons a. Occurs when the summated postsynaptic potential is excitatory but has not reached the threshold b. Another excitatory signal can then excite the membrane quite easily Electrical Events During Inhibition • Special Functions of Dendrites for Exciting Neurons a. Large spatial field of excitation of the dendrites- 80-95% of all presynaptic terminals of the anterior motor neuron terminate on dendrites b. Most dendrites cannot transmit APs but they can transmit signals by ion conduction of the fluids in cytoplasm Electrical Events During Inhibition • Decrement of Electrotonic Conduction in the DendritesGreater Excitatory or Inhibitory Effect by Synapses Located Near the Soma Fig. 45.11 Electrical Events During Inhibition • Summation of Excitation and Inhibition in Dendrites Fig. 45.11 Electrical Events During Inhibition •Relation of State of Excitation of the Neuron to Rate of Firing- excitatory state is the summated degree of excitatory drive to the neuron Fig. 45.12 Response characteristics of different types of neurons to different levels of excitatory state Special Characteristics of Synaptic Transmission • Fatigue of Synaptic Transmission • Effect of Acidosis or Alkalosis • Effect of Hypoxia • Effects of Drugs • Synaptic Delay