Synapse

CNS

1. - Dr. Chintan Synapse

2. Sensory System

3. Motor System

4. CNS Synapses information is transmitted in the CNS mainly in the form of nerve action potentials, called simply “nerve impulses,” through a succession of neurons, one after another. However, in addition, each impulse (1) may be blocked in its transmission from one neuron to the next, (2) may be changed from a single impulse into repetitive impulses , or (3) may be integrated with impulses from other neurons to cause highly complicated patterns of impulses in successive neurons . All these functions - synaptic functions of neurons .

5. Definition The junction between two neurons is called synapse . This word was first introduced by SHERRINGTON .

6. Characteristic It is not an Anatomical continuity but just a Physiological contiguity ( contact without connection ). Thus a synapse is a functional junction between two neurons . It is the most important determinant of CNS function as information is passed from one neuron to other via a synapse.

7. Functions of synapse 1) Transmission of impulses to and fro from periphery to CNS and vice versa . 2) Modification of impulses, integration of impulses or changing or blocking of impulses . 3) Higher function of CNS like learning, memory etc are possible due to synapses.

8. Types of synapses 1) Anatomical classification - depending upon the part of neurons involved . 2) Physiological classification - depending upon the nature of transmission through the synapse . 3) According to number of neurons involved.

9. Types of Synapses — Chemical and Electrical Almost all the synapses used for signal transmission in the CNS of the human being are chemical synapses . In these, the first neuron secretes at its nerve ending synapse a chemical substance called a neurotransmitter and this transmitter in turn acts on receptor proteins in the membrane of the next neuron to excite the neuron, inhibit it, or modify its sensitivity in some other way. Acetylcholine (Ach), norepinephrine (NE), epinephrine (E), histamine, gamma-aminobutyric acid (GABA), glycine, serotonin and glutamate

10. Types of Synapses — Chemical and Electrical Electrical synapses are characterized by direct open fluid channels that conduct electricity from one cell to the next . Most of these consist of small protein tubular structures called gap junctions that allow free movement of ions from the interior of one cell to the interior of the next . Only a few gap junctions have been found in CNS it is by way of gap junctions and other similar junctions that action potentials are transmitted from one smooth muscle fiber to the next in visceral smooth muscle and from one cardiac muscle cell to the next in cardiac muscle

11. “One-Way” Conduction Chemical synapses always transmit the signals in one direction: that is, from the neuron that secretes the transmitter substance , called the presynaptic neuron , to the neuron on which the transmitter acts , called the postsynaptic neuron . This is the principle of one-way conduction at chemical synapses, and it is quite different from conduction through electrical synapses, which often transmit signals in either direction .

12. Anatomical classification 1) Axodendritic synapse - Type I (most common ) - motor neurons of spinal cord , excitatory synapse in cerebral cortex , climbing fibers of cerebellum . 2) Axosomatic synapse - Type-II (less common ) - motor neurons of spinal cord , basket cells of cerebellum , autonomic ganglia . 3) Axoaxonic synapse (least common) - seen in spinal cord . 4) Dendrodendritic synapse (rare ) - seen in olfactory bulb between mitral and granule cell.

13. Physiological or functional classification 1) Chemical Synapse 2) Electrical Synapse 3) Conjoint Synapse (where both chemical and electrical transmission coexists)

14. Differences between chemical and electrical synapse Chemical synapse 1) Transmission is by Neurotransmitters . 2) Most of the synapses are of this type. 3) They conduct in one direction . 4) More vulnerable to fatigue on repeated stimulation, hypoxia, PH changes. 5) Slow speed causing synaptic delay as it allows for large no of synapses per neuron. Electrical synapse 1) Transmission is by gap junctions – low resistance bridges - ions pass easily 2) Seen in some places eg retina, olfactory bulb, hippocampus, cerebral cortex. 3) They conduct in both directions. 4) Insensitive to hypoxia. 5) Rapid efficient transmission with no delay as not too many synapses per neuron.

15. Physiologic Anatomy of the Synapse

16. Structure of a synapse Pre synaptic terminal Pre synaptic membrane Synaptic cleft Postsynaptic terminal or process Postsynaptic membrane

17. Presynaptic terminals Electron Microscope studies show that there are various anatomical forms hence called by different names, terminal knobs, buttons, end feet or synaptic knobs . There is no myelin sheath and each knob has Mitochondria and synaptic vesicles containing neurotransmitter substance . Mitochondria provides ATP for synthesis of NTs

18. Pre synaptic terminals on dendrites & soma 1) Some of these presynaptic terminals are excitatory — that is, they secrete a transmitter substance that excites the postsynaptic neuron. 2) But other presynaptic terminals are inhibitory — they secrete a transmitter substance that inhibits the postsynaptic neuron

19. Synaptic vesicles- different types 1) Round or spherical clear vesicles Have excitatory NTs eg , Ach, Glutamate 2) Flat clear vesicles Have inhibitory NTs eg , GABA, Glycine 3) Small dense core vesicles Have catecholamines - E/NE , Dopamine 4) Large dense core vesicles Peptide NTs – Endorphin, Enkephalin

20. Axoplasmic transport of vesicles The vesicles and the proteins contained in their walls are synthesized in the Golgi apparatus in the neuronal cell body and migrate down the axon to the endings by fast Axoplasmic transport .

21. Presynaptic membrane It is the axonal membrane of the synaptic terminal. It contains large no. of calcium gated channels (Active zone - a thickened area) These voltage gated Ca channels open when an Action Potential depolarizes the presynaptic membrane . Calcium causes the release of NTs

22. Synaptic cleft It is a small gap of 200-300 angstrom width ( 20-40 nm) between pre and postsynaptic membranes . It is filled with ECF containing some glycoproteins . The NTs is released in this cleft .

23. Post synaptic terminal or process It is the name of the receiving neuron eg dendritic spine, or soma , where synaptic knob synapses .

24. Post synaptic membrane It is the membrane lining the postsynaptic process . It contains a large no of receptor proteins which protrude into the synaptic cleft . NTs released in the cleft bind to receptor proteins to cause the effect

25. Mech - AP causes release of NTs from presynaptic terminal - Ca role The presynaptic membrane contains large numbers of voltage-gated calcium channels . When an action potential depolarizes the presynaptic membrane, these calcium channels open and allow large numbers of calcium ions to flow into the terminal . The quantity of transmitter substance that is then released from the terminal into the synaptic cleft is directly related to the number of calcium ions that enter.

26. When the calcium ions enter the presynaptic terminal - they bind with special protein molecules on the inside surface of the presynaptic membrane, called release sites . This binding in turn causes the release sites to open through the membrane , allowing a few transmitter vesicles to release their transmitter into the cleft after each single action potential.

27. Clinical application Clinically, tetanus toxin causes spastic paralysis by blocking presynaptic transmitter release in the CNS and botulism causes flaccid paralysis by blocking the release of acetylcholine at the neuromuscular junction . On the positive side, however, local injection of small doses of botulinum toxin has proved effective in the treatment of a wide variety of conditions characterized by muscle hyperactivity. Examples include injection into the lower esophageal sphincter to relieve achalasia and injection into facial muscles to remove wrinkles

28. Receptors on postsynaptic membrane They have two important components- (1) a binding component that protrudes outward from the membrane into the synaptic cleft— here it binds the neurotransmitter coming from the presynaptic terminal and (2) ionophore component that passes all the way through the postsynaptic membrane to the interior of the postsynaptic neuron .

29. Ionophore component is of two types (1) an ion channel that allows passage of specified types of ions through the membrane or (2) a “ second messenger ” activator is a molecule that protrudes into the cell cytoplasm and activates one or more substances inside the postsynaptic neuron. These substances in turn serve as “second messengers” to increase or decrease specific cellular functions .

30. Ion channels- two types (1) cation channels that most often allow sodium ions to pass when opened, but sometimes allow potassium and/or calcium ions as well, and (2) anion channels that allow mainly chloride ions to pass but also minute quantities of other anions.

31. Cation channel opens - excitation anion channel opens - inhibition when cation channels open and allow positively charged sodium ions to enter, the positive electrical charges of the sodium ions will in turn excite this neuron . Therefore , a transmitter substance that opens cation channels is called an excitatory transmitter . Conversely, opening anion channels allows negative electrical charges to enter, which inhibits the neuron. Therefore , transmitter substances that open these channels are called inhibitory transmitters

32. Rapid opening or closing of ion channels When a transmitter substance activates an ion channel, the channel usually opens within a fraction of a millisecond ; when the transmitter substance is no longer present, the channel closes equally rapidly . The opening and closing of ion channels provide a means for very rapid control of postsynaptic neurons.

33. Second messenger system - via G protein causes 4 effects 1) opening an ion channel (K channel) in the membrane of the second neuron ; 2) activating an enzyme system in the neuron’s membrane Eg – ATP- cAMP or GTP – cGMP 3) activating an intracellular enzyme system ; 4) causing gene transcription in the second neuron for structural changes.

34. Post – Synaptic events

35. Excitatory or Inhibitory Receptors Excitation 1. Opening of sodium channels to allow large numbers of positive electrical charges to flow to the interior of the postsynaptic cell . This raises the intracellular membrane potential in the positive direction up toward the threshold level for excitation . 2. Depressed conduction through chloride or potassium channels This decreases the diffusion of negatively charged chloride ions to the inside of the postsynaptic neuron or decreases the diffusion of positively charged potassium ions to the outside . the effect is to make the internal membrane potential more positive than normal , which is excitatory

36. Excitatory or Inhibitory Receptors Excitation 3. Various changes in the internal metabolism of the postsynaptic neuron to excite cell activity or, to increase the number of excitatory membrane receptors or decrease the number of inhibitory membrane receptors Inhibition 1. Opening of chloride ion channels through the postsynaptic neuronal membrane. This allows rapid diffusion of negatively charged chloride ions from outside the postsynaptic neuron to the inside , thereby carrying negative charges inward and increasing the negativity inside , which is inhibitory.

37. Excitatory or Inhibitory Receptors Inhibition 2. Increase in conductance of potassium ions out of the neuron. This allows positive ions to diffuse to the exterior , which causes increased negativity inside the neuron; this is inhibitory . 3. Activation of receptor enzymes that inhibit cellular metabolic functions increase the number of inhibitory synaptic receptors or decrease the number of excitatory receptors.

38. Synaptic transmission Arrival of A P in axon terminal (synaptic knob ) --- Depolarization of presynaptic terminal --- Opening of voltage gated Ca channels in presynaptic memb --- Influx of Ca from ECF of synaptic cleft into presynaptic terminal --- exocytosis of vesicles & release of NTs into synaptic cleft --- Binds to receptors on post synaptic membrane to form a complex

39. Electrical Events

40. Excitatory NT- Na entry – EPSP - AP if excitatory then opening of Na channels with influx of Na from ECF into postsynaptic --- Development of EPSP --- With more & more opening of Na channels in initial segment of axon --- When excitation reaches critical level --- Action Potential develops which spreads through the axon of postsynaptic neuron. Glutamate is one such excitatory NT.

41. Inhibitory NT - Cl, K - IPSP If it is an inhibitory synapse then NT --- Receptor complex causes opening of K or Cl channels --- causing Hyperpolarisation --- IPSP --- inhibition thus occurs . GABA, Glycine are inhibitory NTs

42. EPSP - Excitatory post synaptic potential It is depolarization of post synaptic memb , produced by excitatory NT eg Glutamate . Ionic basis of EPSP – excitatory NT binds to receptor protein to open up ligand gated Na channels of postsynaptic memb . Thus rapid entry of Na ions change RMP of -65mv to -45mv called EPSP . Discharge of single presynaptic terminal does not cause potential change of -65 to -45mv so simultaneous discharge of many (40-80) leads to this thus causing Summation

43. Excitatory Postsynaptic Potential - EPSP

44. Properties of EPSP 1) It is similar to receptor potential & end plate potential . 2) It is non propagative hence differs from AP . 3 ) It does not obey All or None law 5) It shows temporal and spatial summation

45. IPSP - Inhibitory post synaptic potential both chloride influx and potassium efflux increase the degree of intracellular negativity, which is called hyperpolarization . This inhibits the neuron because the membrane potential is even more negative than the normal intracellular potential. Therefore, an increase in negativity beyond the normal resting membrane potential level is called an inhibitory postsynaptic potential (IPSP) .

46. Inhibitory Postsynaptic Potential - IPSP

47. Synaptic Transmitters One group - small-molecule, rapidly acting transmitters - most acute responses of the nervous system , transmission of sensory signals to the brain motor signals back to the muscles. The other group is made up of a large number of neuropeptides of much larger molecular size that are slowly acting - More prolonged actions long-term changes in numbers of neuronal receptors , long-term opening or closure of certain ion channels , Long term changes in numbers of synapses or sizes of synapses .

48. Initial Segment of the Axon When the EPSP rises high enough in the positive direction , there comes a point at which this initiates an action potential in the neuron. the action potential begins in the initial segment of the axon where the axon leaves the neuronal soma. The main reason for this point of origin of the action potential is that the soma has relatively few voltage-gated sodium channels in its membrane, which makes it difficult for the EPSP to open the required number of sodium channels to elicit an action potential .

49. Initial Segment of the Axon the membrane of the initial segment has seven times as great a concentration of voltage-gated sodium channels as does the soma and, therefore, can generate an action potential with much greater ease than can the soma. The EPSP that will elicit an action potential in the axon initial segment is between +10 and +20 millivolts . This is in contrast to the +30 or +40 millivolts or more required on the soma .

50. Excitation and spread of AP

51. Types of synaptic inhibition 1. Pre synaptic inhibition 2. Renshaw Cell inhibition 3. Post synaptic inhibition

52. Presynaptic Inhibition In addition to inhibition caused by inhibitory synapses operating at the neuronal membrane - postsynaptic inhibition , another type of inhibition often occurs at the presynaptic terminals before the signal ever reaches the synapse - presynaptic inhibition Presynaptic inhibition is caused by release of an inhibitory substance onto the outsides of the presynaptic nerve fibrils before their own endings terminate on the postsynaptic neuron – GABA This has a specific effect of opening anion channels, allowing large numbers of chloride ions to diffuse into the terminal fibril. The negative charges of these ions inhibit synaptic transmission because they cancel much of the excitatory effect of the positively charged sodium ions that also enter the terminal fibrils when an action potential arrives.

53. Importance of pre synaptic inhibition Presynaptic inhibition occurs in many of the sensory pathways in the nervous system. Seen in pain pathways – gating of pain transmission - so pain control occurs . adjacent sensory nerve fibers often mutually inhibit one another , which minimizes sideways spread and mixing of signals in sensory tracts

54. Renshaw cell inhibition Here neurons inhibit themselves in a negative feedback manner . It is seen in spinal cord which has motor neurons like alpha motor neurons situated in anterior gray horn . Renshaw cell is a type of motor neuron near alpha motor neuron . When alpha sends impulses via ant nerve root fibres - some of its impulses reach the Renshaw cells by collaterals, which excites them . Renshaw cell in turn sends inhibitory impulses to alpha motor neurons and thus inhibits them .

55. Post synaptic inhibition It is also called direct inhibition . It is due to the development of IPSP . It is due to failure of production of AP in post synaptic membrane because of release of inhibitory NT from pre synaptic terminal . Sometimes it may occur also due to refractory period – postsynaptic membrane can be refractory to excitation because it has just fired and is in refractory state .

56. Feed forward inhibition Seen in the cerebellum in basket cells and Purkinje cells . When impulse passes through afferent nerve both the cells are stimulated but basket cells in turn inhibit Purkinje cells. So duration of discharge by Purkinje cells is reduced and output from it is controlled.

57. Significance of synaptic inhibition 1) It offers restriction over neurons and muscles so that excess stimuli are inhibited and various movements are performed properly and accurately . 2) Inhibition helps to select exact no of impulses and to block the excess ones . 3) Poison like strychnine destroys all inhibitory functions causing convulsions - post synaptic inhibition . 4) In disorders like Parkinsonism inhibitory system is impaired resulting in rigidity .

58. Fate of NT The NT is inactivated as follows , 1) By diffusion out of the cleft 2) Enzymatic degradation of NT , eg dissociation of Ach by acetylcholinesterase enzyme . 3) Reuptake of NT back into presynaptic membrane.

59. Importance of inhibition Persistence of NT in synaptic cleft produces prolong stimulation of post synaptic neuron in response to a single electrical impulse in pre synaptic neuron.

60. Properties of synapse 1) One way conduction (Law of forward conduction). 2) Synaptic delay. 3) Synaptic fatigue. 4) Convergence and Divergence. 5) Summation. 6) Occlusion phenomenon. 7) Subliminal fringe effect.

61. Properties of synapse 8) Facilitation. 9) Reverberation. 10) Reciprocal inhibition. 11) After discharge. 12) Effect of acidosis and hypoxia. 13) Effect of drugs. 14) Synaptic plasticity and learning

62. One Way Conduction The chemical synapse allows only one way conduction i.e. from presynaptic to postsynaptic neuron and never in opposite direction. This is also called Bell- Magendie Law . It occurs because NT is present only at presynaptic area and postsynaptic has specific receptor sites . Hence antidromically conducted signal dies out at soma due to lack of chemical substance. Significance - for orderly neural function .

63. Synaptic Delay During transmission of a neuronal signal from a presynaptic neuron to a postsynaptic neuron , a certain amount of time is consumed in the process of (1) discharge of the transmitter substance by the presynaptic terminal, (2) diffusion of the transmitter to the postsynaptic neuronal membrane, (3) action of the transmitter on the membrane receptor, (4) action of the receptor to increase the membrane permeability, (5) inward diffusion of sodium to raise the excitatory postsynaptic potential to a high enough level to elicit an action potential . 0.5 millisecond - synaptic delay.

64. Significance of delay 1) Conduction along a chain of neurons is slow if there are many synapses . 2) It is possible to know if reflex pathway is monosynaptic or polysynaptic by measuring the delay in transmission of impulse from dorsal to ventral root across the spinal cord.

65. Summation It is of two types, 1)Spatial Summation — When many presynaptic terminals are stimulated simultaneously there is summation or fusion of effects in postsynaptic neuron . 2)Temporal Summation — When one presynaptic terminal is stimulated repeatedly . Summation causes progressive increase in EPSP which causes membrane potential to reach firing level.

66. Spatial Summation

67. Temporal Summation Each time a presynaptic terminal fires, the released transmitter substance opens the membrane channels for at most a millisecond But the changed postsynaptic potential lasts up to 15 milliseconds after the synaptic membrane channels have already closed. Therefore, a second opening of the same channels can increase the postsynaptic potential to a still greater level, and the more rapid the rate of stimulation , the greater the postsynaptic potential becomes. Thus, successive discharges from a single presynaptic terminal , if they occur rapidly enough, can add to one another ; that is, they can “summate.” - temporal summation .

68. Occlusion phenomenon It means that when there is simultaneous stimulation of two presynaptic neurons the response is less than the sum total of the response obtained when they are stimulated separately . For eg presynaptic neuron A & B upon stimulation separately each stimulates 10 post synaptic neurons making total of 20, But when A & B are stimulated simultaneously they stimulate less eg 15 postsynaptic neurons only . This decrease in response is due to some post synaptic neurons being common to both presynaptic neurons . This is due to overlapping of afferent fibers in their central distribution

69. Occlusion the response to stimulation of B and C together is not as great as the sum of responses to stimulation of B and C separately, because B and C both end on neuron Y . This decrease in expected response, due to presynaptic fibers sharing postsynaptic neurons , is called occlusion

70. Occlusion (2+2=3)

71. Subliminal fringe 2+2 = 5 Opposite to occlusion Response obtained by the simultaneous stimulation of two presynaptic neurons is greater than the sum total of the response obtained when they are separately stimulated Suppose stimulation of neuron A causes stimulation of 5 post synaptic neurons and stimulation of neuron B causes stimulation of 5 postsynaptic neurons and then sum of neurons stimulated is 10 But when neuron A and B are stimulated simultaneously number of the postsynaptic neurons stimulated is more than ten.

72. Subliminal fringe 2+2 = 5 Subliminal means below threshold Fringe means border . Thus the post synaptic neurons are said to be in a subliminal fringe if they are not discharged by activity of pre synaptic neurons but their excitability is increased . Those which have discharged are in discharging zone and have fired due to development of AP in them whereas those in periphery ( fringe) are excited up to sub threshold level only and AP is not development in them .

73. Neuronal pool – supra, sub, thresold

74. Synaptic plasticity Plasticity refers to the capability of being easily moulded or changed . Synaptic transmission can easily be increased or decreased on the basis of past experience . These changes can be presynaptic or postsynaptic in location and play an important role in learning and memory.

75. Forms of synaptic plasticity 1) Post tetanic Potentiation 2) Long term Potentiation 3) Long term Depression 4) Habituation 5) Sensitization

76. Post tetanic Potentiation Tetanizing stimuli in pre synaptic neuron results in increase postsynaptic potentials lasting for minutes to hours . Cause is increase Ca influx in pre synaptic neuron which increases release of NTs. Hence response is potentiated.

77. Long term Potentiation If post tetanic potentiation gets more prolonged and lasts for days it is called as long term potentiation . Cause is due to increase intracellular Ca in post synaptic neuron rather than presynaptic . This occurs in HIPPOCAMPUS commonly.

78. Long term depression It is opposite of long term potentiation . There is slower stimulation of presynaptic neurons, with decrease in synaptic conduction following decreased Ca influx . Seen commonly in Hippocampus and Cerebellum

79. Habituation When a stimulus is benign and is repeated over and over, the response to the stimulus gradually disappears (habituation). This is associated with decreased release of neurotransmitter from the presynaptic terminal because of decreased intracellular Ca2 +. The decrease in intracellular Ca2+ is due to a gradual inactivation of Ca2+ channels . It can be short-term, or it can be prolonged if exposure to the benign stimulus is repeated many times .

80. Sensitization There is prolong occurrence of increased postsynaptic responses after a stimulus is paired once or several times with a noxious stimulus . It is due to Ca mediated changes - adenyl cyclase that results in greater production of cAMP .

81. Facilitation When presynaptic neuron is stimulated with several successive individual stimuli , each stimulus may evoke a larger post synaptic potential than that evoked by the previous stimulus. This is called as Facilitation .

82. “Facilitation” of Neurons Often the summated postsynaptic potential is excitatory but has not risen high enough to reach the threshold for firing of the postsynaptic neuron. When this happens, the neuron is said to be facilitated – its membrane potential is nearer the threshold for firing than normal, but not yet at the firing level . Consequently, another excitatory signal entering the neuron from some other source can then excite the neuron very easily . Diffuse signals in the nervous system often facilitate large groups of neurons so that they can respond quickly and easily to signals arriving from other sources.

83. Fatigue of Synaptic Transmission When excitatory synapses are repetitively stimulated at a rapid rate , the number of discharges by the postsynaptic neuron is at first very great , but the firing rate becomes progressively less in succeeding milliseconds or seconds - fatigue of synaptic transmission . Fatigue is an exceedingly important characteristic of synaptic function because when areas of the nervous system become overexcited , fatigue causes them to lose this excess excitability after awhile . Fatigue is probably the most important means by which the excess excitability of the brain during an epileptic seizure is finally unresponsive so that the seizure stops. Thus, the development of fatigue is a protective mechanism against excess neuronal activity .

84. Fatigue of Synaptic Transmission The mechanism of fatigue is mainly exhaustion or partial exhaustion of the stores of transmitter substance in the presynaptic terminals. The excitatory terminals on many neurons can store enough excitatory transmitter to cause only about 10,000 action potentials , and the transmitter can be exhausted in only a few seconds to a few minutes of rapid stimulation . Part of the fatigue process probably results from two other factors as well: (1) progressive inactivation of many of the postsynaptic membrane receptors and (2) slow development of abnormal concentrations of ions inside the postsynaptic neuronal cell.

85. Effect of Acidosis or Alkalosis Alkalosis greatly increases neuronal excitability - rise in arterial blood pH from the 7.4 norm to 7.8 to 8.0 often causes cerebral epileptic seizures because of increased excitability of some or all of the cerebral neurons. This can be demonstrated especially well by asking a person who is predisposed to epileptic seizures to overbreathe overbreathing blows off carbon dioxide and therefore elevates the pH of the blood momentarily , but even this short time can often precipitate an epileptic attack. acidosis greatly depresses neuronal activity - a fall in pH from 7.4 to below 7.0 usually causes a comatose state - diabetic or uremic acidosis

86. Effect of Hypoxia Neuronal excitability is also highly dependent on an adequate supply of oxygen. Cessation of oxygen for only a few seconds can cause complete inexcitability of some neurons. This is observed when the brain’s blood flow is temporarily interrupted, because within 3 to 7 seconds , the person becomes unconscious.

87. Effect of Drugs caffeine, theophylline, and theobromine, which are found in coffee, tea, and cocoa , respectively, all increase neuronal excitability, presumably by reducing the threshold for excitation of neurons . Most anesthetics increase the neuronal membrane threshold for excitation and thereby decrease synaptic transmission at many points in the nervous system. Because many of the anaesthetics are especially lipid soluble - change the physical characteristics of the neuronal membranes , making them less responsive to excitatory agents .

88. Divergence of Signals An amplifying type of divergence - an input signal spreads to an increasing number of neurons as it passes through successive orders of neurons in its path. corticospinal pathway in its control of skeletal muscles, with a single large pyramidal cell in the motor cortex capable of exciting as many as 10,000 muscle fibers. divergence into multiple tracts - the signal is transmitted in two directions information transmitted up the dorsal columns of the spinal cord takes two courses in the lower part of the brain: (1) into the cerebellum and (2) on through the lower regions of the brain to the thalamus and cerebral cortex. in the thalamus, almost all sensory information is relayed both into still deeper structures of the thalamus and at the same time to separate regions of the cerebral cortex

89. Convergence of Signals Convergence means signals from multiple inputs uniting to excite a single neuron. convergence from a single source - multiple terminals from a single incoming fiber tract terminate on the same neuron. The importance of this is that neurons are never excited by an action potential from a single input terminal . But action potentials converging on the neuron from multiple terminals provide enough spatial summation to bring the neuron to the threshold required for discharge .

90. Convergence of Signals Convergence can also result from input signals (excitatory or inhibitory) from multiple sources the interneurons of the spinal cord receive converging signals from (1) peripheral nerve fibers entering the cord, (2) propriospinal fibers passing from one segment of the cord to another, (3) corticospinal fibers from the cerebral cortex, and (4) several other long pathways descending from the brain into the spinal cord. Then the signals from the interneurons converge on the anterior motor neurons to control muscle function. Such convergence allows summation of information from different sources, and the resulting response is a summated effect of all the different types of information . Convergence is one of the important means by which the CNS correlates, summates, and sorts different types of information.

91. Neuronal Circuit with Both Excitatory and Inhibitory Signals Sometimes an incoming signal to a neuronal pool causes an output excitatory signal going in one direction and at the same time an inhibitory signal going elsewhere . at the same time that an excitatory signal is transmitted by one set of neurons in the spinal cord to cause forward movement of a leg, an inhibitory signal is transmitted through a separate set of neurons to inhibit the muscles on the back of the leg so that they will not oppose the forward movement. This type of circuit is characteristic for controlling all antagonistic pairs of muscles , and it is called the reciprocal inhibition circuit .

92. Afterdischarge a signal entering a pool causes a prolonged output discharge, called afterdischarge , lasting a few milliseconds to as long as many minutes after the incoming signal is over. Synaptic Afterdischarge . When excitatory synapses discharge on the surfaces of dendrites or soma of a neuron, a postsynaptic electrical potential develops in the neuron and lasts for many milliseconds , especially when some of the long-acting synaptic transmitter substances are involved. As long as this potential lasts, it can continue to excite the neuron , causing it to transmit a continuous train of output impulses Thus, as a result of this synaptic “afterdischarge” mechanism alone, it is possible for a single instantaneous input signal to cause a sustained signal output (a series of repetitive discharges) lasting for many milliseconds.

93. Reverberatory (Oscillatory) Circuit Such circuits are caused by positive feedback within the neuronal circuit that feeds back to re-excite the input of the same circuit. So, once stimulated , the circuit may discharge repetitively for a long time. Involvement of only a single neuron . the output neuron simply sends a collateral nerve fiber back to its own dendrites or soma to restimulate itself . once the neuron discharges , the feedback stimuli can keep the neuron discharging for a prolonged time thereafter

94. Reverberatory (Oscillatory) Circuit a few additional neurons in the feedback circuit , which causes a longer delay between initial discharge and the feedback signal both facilitatory and inhibitory fibers impose on the reverberating circuit. A facilitatory signal enhances the intensity and frequency of reverberation , whereas an inhibitory signal depresses or stops the reverberation. most reverberating pathways are constituted of many parallel fibers - At each cell station, the terminal fibrils spread widely . The total reverberating signal can be either weak or strong , depending on how many parallel nerve fibers are temporarily involved in the reverberation

95. Receptor Potentials Whatever the type of stimulus that excites the receptor , its immediate effect is to change the membrane electrical potential of the receptor . This change in potential is called a receptor potential . Different receptors can be excited in one of several ways to cause receptor potentials: (1) by mechanical deformation of the receptor , which stretches the receptor membrane and opens ion channels; (2) by application of a chemical to the membrane , which also opens ion channels; (3) by change of the temperature of the membrane , which alters the permeability of the membrane; or (4) by the effects of electromagnetic radiation, such as light on a retinal visual receptor , which either directly or indirectly changes the receptor membrane characteristics and allows ions to flow through membrane channels

96. Adaptation of Receptors characteristic of all sensory receptors is that they adapt either partially or completely to any constant stimulus after a period of time. when a continuous sensory stimulus is applied, the receptor responds at a high impulse rate at first and then at a progressively slower rate until finally the rate of action potentials decreases to very few or often to none at all. complete adaptation of a mechanoreceptor is about 2 days , which is the adaptation time for many carotid and aortic baroreceptors . the non mechanoreceptors — the chemoreceptors and pain receptors never adapt completely.

97. Slowly Adapting Receptors - tonic receptors Slowly adapting receptors continue to transmit impulses to the brain as long as the stimulus is present - they keep the brain constantly informed of the status of the body and its relation to its surroundings . impulses from the muscle spindles and Golgi tendon apparatuses allow the nervous system to know the status of muscle contraction and load on the muscle tendon (1) receptors of the macula in the vestibular apparatus , (2) pain receptors , (3) baroreceptors of the arterial tree, and (4 ) chemoreceptors of the carotid and aortic bodies.

98. Rapidly Adapting Receptors Rate Receptors, Movement Receptors, Phasic Receptors Receptors that adapt rapidly cannot be used to transmit a continuous signal because these receptors are stimulated only when the stimulus strength changes - they react strongly while a change is actually taking place. sudden pressure applied to the tissue excites pacinian corpuscle for a few milliseconds , and then its excitation is over even though the pressure continues. But later, it transmits a signal again when the pressure is released . the pacinian corpuscle is important in informing the nervous system of rapid tissue deformations , but it is useless for transmitting information about constant conditions in the body.

99. Thank You…