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Unsourced material may be challenged and removed. A neurologist usually recommends vagus nerve stimulation after they have decided that phamacalogically and surgically they can go no further. These children appear to be timid and shy and represent about 20 percent of volunteer Caucasian samples. This modulation is mediated by the neurotransmitter acetylcholine and downstream changes to ionic currents and calcium of heart cells. Glutamate speeds up the neurons in your mind and enhances the connections between neurons. Or take 1 drop of rosemary internally with a smoothie or cup of soup.
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These nuclei include the Edinger-Westphal pupillary nucleus, superior and inferior salivatory nuclei, dorsal motor nucleus of the vagus, and adjacent reticular nuclei. Axons preganglionic fibers of the visceral cranial nuclei course through the oculomotor, facial, glossopharyngeal, and vagus cranial nerves.
The preganglionic fibers from the Edinger-Westphal nucleus traverse the oculomotor nerve and synapse in the ciliary ganglion in the orbit; axons of the ciliary ganglion cells innervate the ciliary muscle and pupillary sphincter see Fig.
The preganglionic fibers of the superior salivatory nucleus enter the facial nerve and, at a point near the geniculate ganglion, form the greater superficial petrosal nerve, through which they reach the sphenopalatine ganglion; postganglionic fibers from the cells of this ganglion innervate the lacrimal gland see also Figs. Other fibers originating in the salivatory nuclei are carried in the facial nerve and traverse the tympanic cavity as the chorda tympani to eventually join the submandibular ganglion.
Cells of this ganglion innervate the submandibular and sublingual glands. Axons of the inferior salivatory nerve cells enter the glossopharyngeal nerve and reach the otic ganglion through the tympanic plexus and lesser superficial petrosal nerve; cells of the otic ganglion send fibers to the parotid gland.
Preganglionic fibers, derived from the dorsal motor nucleus of the vagus and adjacent visceral nuclei in the lateral reticular formation mainly the nucleus ambiguus , enter the vagus nerve and terminate in ganglia situated in the walls of many thoracic and abdominal viscera.
The ganglionic cells give rise to short postganglionic fibers that activate smooth muscle and glands of the pharynx, esophagus, and gastrointestinal tract the vagal innervation of the colon is somewhat uncertain but considered to extend up to the descending colon and of the heart, pancreas, liver, gallbladder, kidney, and ureter. The sacral part of the parasympathetic system originates in the lateral horn cells of the second, third, and fourth sacral segments. Axons of these sacral neurons, constituting the preganglionic fibers, traverse the sacral spinal nerve roots of the cauda equina and synapse in ganglia that lie within the walls of the distal colon, bladder, and other pelvic organs.
Thus, the sacral autonomic neurons, like the cranial ones, have long preganglionic and short postganglionic fibers, a feature that permits a circumscribed influence upon the target organ. In organs containing smooth muscle that is innervated by parasympathetic fibers and therefore not under voluntary control, there is a parallel innervation of adjacent voluntary striated muscle by anterior horn cells.
For example, the neurons that activate the external sphincter of the bladder voluntary muscle differ from those that supply the smooth muscle of the internal sphincter as discussed further on. In , Onufrowicz calling himself Onuf described a discrete group of relatively small cells in the anterior horns of sacral segments 2 to 4.
These neurons were originally thought to be autonomic in function, mainly because of their histologic features. There is now evidence that they are somatomotor, innervating the skeletal muscle of the external urethral and anal sphincters Holstege and Tan.
Neurons in sacral cord segments located in a region analogous to the intermediolateral cell column of the sympathetic nervous system see later , innervate the detrusor and internal sphincter of the bladder wall. In passing, it is worth noting that in motor system disease, in which bladder and bowel functions are usually preserved until late in the disease, the neurons in the Onuf nucleus, in contrast to other somatomotor neurons in the sacral cord, tend not to be involved in the degenerative process Mannen et al.
There are elaborate connections between supranuclear centers, mainly in the hypothalamus, to the pupillary sphincters, lacrimal and salivary glands that course the brainstem. With regard to the supranuclear innervation of parasympathetic nuclei in the sacral segments, little is known.
There appear to be connections to these neurons from the hypothalamus, locus ceruleus, and pontine micturition centers but their course in the human spinal cord has not been identified with certainty. The preganglionic neurons of the sympathetic division originate in the intermediolateral cell column of the spinal gray matter, from the eighth cervical to the second lumbar segments.
Low and Dyck have estimated that each segment of the cord contains approximately 5, lateral horn cells and that there is an attrition of 5 to 7 percent per decade in late adult life. The axons of the nerve fibers originating in the intermediolateral column are of small caliber and are myelinated; when grouped, they form the white communicating rami as shown in Fig. These preganglionic fibers synapse with the cell bodies of the postganglionic neurons, which are collected into two large ganglionated chains or cords, one on each side of the vertebral column paravertebral ganglia , and several single prevertebral ganglia.
These constitute the sympathetic ganglia. Axons of the sympathetic ganglion cells are also of small caliber but are unmyelinated. Most of the postganglionic fibers pass via gray communicating rami to their adjacent spinal nerves of T5 to L2; they supply blood vessels, sweat glands, and hair follicles, and also form plexuses that supply the heart, bronchi, kidneys, intestines, pancreas, bladder, and sex organs.
The postganglionic fibers of the prevertebral ganglia located in the retroperitoneal posterior abdomen rather than paravertebrally, along the sides of the spinal column form the hypogastric, splanchnic, and mesenteric plexuses, which innervate the glands, smooth muscle, and blood vessels of the abdominal and pelvic viscera see Fig.
The sympathetic innervation of the adrenal medulla is unique in that its secretory cells receive preganglionic fibers directly, via the splanchnic nerves.
This is an exception to the rule that organs innervated by the autonomic nervous system receive only postganglionic fibers. This special arrangement can be explained by the fact that cells of the adrenal medulla are the morphologic homologues of the postganglionic sympathetic neurons and secrete epinephrine and norepinephrine the postganglionic transmitters directly into the bloodstream.
In this way, the sympathetic nervous system and the adrenal medulla act in unison to produce diffuse effects, as one would expect from their role in emergency reactions. There are 3 cervical superior, middle, and inferior, or stellate , 11 thoracic, and 4 to 6 lumbar sympathetic ganglia. The head receives its sympathetic innervation from the eighth cervical and first two thoracic cord segments, the fibers of which pass through the inferior to the middle and superior cervical ganglia.
Postganglionic fibers from cells of the superior cervical ganglion follow the internal and external carotid arteries and innervate the blood vessels and smooth muscle, as well as the sweat, lacrimal, and salivary glands of the head.
Included among these postganglionic fibers, issuing mainly from T1, are the pupillodilator fibers and those innervating the Müller muscle of the upper eyelid it connects the upper tarsus to the undersurface of the levator ; there is a separate small inferior tarsus muscle that is also sympathetically innervated. The arm receives its postganglionic innervation from the inferior cervical ganglion and uppermost thoracic ganglia the two are fused to form the stellate ganglion.
The cardiac plexus and other thoracic sympathetic nerves are derived from the stellate ganglion and the abdominal visceral plexuses, from the fifth to the ninth or tenth thoracic ganglia.
The lowermost thoracic ganglia have no abdominal visceral connections; their axons course rostrally and caudally in the sympathetic chain.
The upper lumbar ganglia supply the descending colon, pelvic organs, and legs. The terminals of autonomic nerves and their junctions with smooth muscle and glands have been more difficult to visualize and study than the motor end plates of striated muscle. As the postganglionic axons enter an organ, usually via the vasculature, they ramify into many smaller branches and disperse, without a Schwann cell covering, to innervate the smooth muscle fibers, the glands, and, in largest number, the small arteries, arterioles, and precapillary sphincters see Burnstock.
Some of these terminals penetrate the smooth muscle of the arterioles; others remain in the adventitia. At the ends of the postganglionic fibers and in part along their course there are swellings that lie in close proximity to the sarcolemma or gland cell membrane; often the muscle fiber is grooved to accommodate these swellings.
The axonal swellings contain synaptic vesicles, some clear and others with a dense granular core. The clear vesicles contain acetylcholine and those with a dense core contain catecholamines, particularly norepinephrine Falck. This is well illustrated in the iris, where nerves to the dilator muscle sympathetic contain dense-core vesicles and those to the constrictor parasympathetic contain clear vesicles. A single nerve fiber innervates multiple smooth muscle and gland cells.
Somewhat arbitrarily, anatomists have declared the autonomic nervous system to be purely efferent motor and secretory in function. However, most autonomic nerves are mixed, also containing afferent fibers that convey sensory impulses from the viscera and blood vessels. The cell bodies of these sensory neurons lie in the posterior root sensory ganglia; some central axons of these ganglionic cells synapse with lateral horn cells of the spinal cord and subserve visceral reflexes; others synapse in the dorsal horn and convey or modulate impulses for conscious sensation.
Secondary afferents carry sensory impulses to certain brainstem nuclei, particularly the nucleus tractus solitarius, as described later, and the thalamus via the lateral spinothalamic and polysynaptic pathways. Integration of autonomic function takes place at two levels, the brainstem and the cerebrum. In the brainstem, the main visceral afferent nucleus is the nucleus tractus solitarius NTS. Cardiovascular, respiratory, and gastrointestinal afferents, carried in cranial nerves X and IX via the nodose and petrosal ganglia, terminate on specific subnuclei of the NTS.
The caudal subnuclei are the primary receiving site for viscerosensory fibers; other less-well-defined areas receive baroreceptor and chemoreceptor information. The caudal NTS integrates these signals and projects to a number of critical areas in the hypothalamus, amygdala, and insular cortex, involved primarily in cardiovascular control, as well as to the pontine and medullary nuclei controlling respiratory rhythms. The NTS therefore serves a critical integratory function for both circulation and respiration, as described further on.
Perhaps the major advance in our understanding of the autonomic nervous system occurred with the elaboration of the autonomic regulating functions of the hypothalamus. Small, insignificant-appearing nuclei in the walls of the third ventricle and in buried parts of the limbic cortex have rich bidirectional connections with autonomic centers in various parts of the nervous system.
As indicated in Chap. The regulatory activity of the hypothalamus is accomplished in two ways, through direct pathways that descend to particular groups of cells in the brainstem and spinal cord, and through the pituitary and thence to other endocrine glands.
The supranuclear regulatory apparatus of the hypothalamus includes three main cerebral structures: The ventromedial prefrontal and cingulate cortices function as the highest levels of autonomic integration.
Stimulation of one frontal lobe may evoke changes in temperature and sweating in the contralateral arm and leg; massive lesions here, which usually cause a hemiplegia, may modify the autonomic functions in the direction of either inhibition or facilitation. Lesions involving the posterior part of the superior frontal and anterior part of the cingulate gyri usually bilateral, occasionally unilateral result in loss of voluntary control of the bladder and bowel.
Most likely a large contingent of these fibers terminates in the hypothalamus, which, in turn, sends fibers to the brainstem and spinal cord. The descending spinal pathways from the hypothalamus are believed to lie ventromedial to the corticospinal fibers. The insular cortex receives projections from the NTS, the parabrachial nucleus of the pons, and the lateral hypothalamic nuclei. Direct stimulation of the insula produces cardiac arrhythmias and a number of other alterations in visceral function.
The cingulate and hippocampal gyri and their associated subcortical structures substantia innominata and the amygdaloid, septal, piriform, habenular, and midbrain tegmental nuclei have been identified as important cerebral autonomic regulatory centers. Together they have been called the visceral brain see Chap.
Of particular importance in autonomic regulation is the amygdala, the central nucleus of which is a major site of origin of projections to the hypothalamus and brainstem. The anatomy and the effects of stimulation and ablation of the amygdala have been discussed in Chap. In addition to the aforementioned central relationships, it should be noted that important interactions between the autonomic nervous system and the endocrine glands occur at a peripheral level.
The best-known example is in the adrenal medulla. A similar relationship pertains to the pineal gland, in which norepinephrine NE released from postganglionic fibers that end on pineal cells stimulates several enzymes involved in the biosynthesis of melatonin. Similarly, the juxtaglomerular apparatus of the kidney and the islets of Langerhans of the pancreas may function as neuroendocrine transducers insofar as they convert a neural stimulus in these cases adrenergic to an endocrine secretion renin, glucagon, and insulin, respectively.
The numerous autonomic—endocrine interactions are elaborated in the next chapter. Finally, there is the essential role that the hypothalamus plays in the initiation and regulation of autonomic activity, both sympathetic and parasympathetic. Sympathetic responses are most readily obtained by stimulation of the posterior and lateral regions of the hypothalamus, and parasympathetic responses from the anterior regions.
The descending sympathetic fibers are largely or totally uncrossed. According to Carmel , fibers from the caudal hypothalamus at first run in the prerubral field, dorsal and slightly rostral to the red nucleus, and then ventral to the ventrolateral thalamic nuclei; then they descend in the lateral tegmentum of the midbrain, pons, and medulla to synapse in the intermediolateral cell column of the spinal cord.
In the medulla, the descending sympathetic pathway is located in the posterolateral retroolivary area, where it is frequently involved in lateral medullary infarctions. In the cervical cord, the fibers run in the posterior angle of the anterior horn Nathan and Smith. According to the latter authors, some of the fibers supplying sudomotor neurons run outside this area but also remain ipsilateral. Jansen and colleagues , by the use of viral vectors in rodents, were able to label certain neurons of the hypothalamus and the ventral medulla that stimulated sympathetic activity in both the stellate ganglion and the adrenal gland.
They hypothesized that this dual control underlies the fight-or-flight response, as described in Chap. By contrast, the pathways of descending parasympathetic fibers are not well defined. Afferent projections from the spinal cord to the hypothalamus have been demonstrated in animals and provide a potential route by which sensation from somatic and possibly visceral structures may influence autonomic responses.
The function of the autonomic nervous system in its regulation of the visceral organs is to a high degree independent of voluntary control and awareness. Furthermore, when the autonomic nerves are interrupted, these organs continue to function the organism survives , but they are no longer as effective in maintaining homeostasis and adapting to the demands of changing internal conditions and external stresses. Viscera have a double-nerve supply, sympathetic and parasympathetic and in general these two parts of the autonomic nervous system exert opposite effects.
For example, the effects of the sympathetic nervous system on the heart are excitatory and those of the parasympathetic inhibitory. However, some structures—sweat glands, cutaneous blood vessels, and hair follicles—receive only sympathetic postganglionic fibers, and the adrenal gland, as indicated earlier, has only a preganglionic sympathetic innervation.
Also, some parasympathetic neurons have been identified in sympathetic ganglia. All autonomic functions are mediated through the release of chemical transmitters. The modern concept of neurohumoral transmission had its beginnings in the early decades of the twentieth century. In , Loewi discovered that stimulation of the vagus nerve released a chemical substance Vagusstoff that slowed the heart. Later this substance was shown by Dale to be acetylcholine ACh. Also, in , Cannon reported that stimulation of the sympathetic trunk released an epinephrine-like substance, which increased the heart rate and blood pressure.
The most important of the autonomic neurotransmitters are ACh and NE. ACh is synthesized at the terminals of axons and stored in presynaptic vesicles until it is released by the arrival of nerve impulses. ACh is released at the terminals of all preganglionic fibers in both the sympathetic and parasympathetic ganglia , as well as at the terminals of all postganglionic parasympathetic and a few special postganglionic sympathetic fibers, mainly those subserving sweat glands.
Of course, ACh is also the chemical transmitter of nerve impulses to the skeletal muscle fibers. Parasympathetic postganglionic function is mediated by two distinct types of ACh receptors: The postganglionic parasympathetic receptors are located within the innervated organ and are muscarinic; i.
As already mentioned the receptors in ganglia, like those of skeletal muscle, are nicotinic; they are not blocked by atropine but are counteracted by other agents e.
It is likely that more than ACh is involved in nerve transmission at a ganglionic level. Many peptides—substance P, enkephalins, somatostatin, vasoactive intestinal peptide, adenosine triphosphate ATP , and nitric oxide—have been identified in the autonomic ganglia, localizing in some cases to the same cell as ACh. Particular neuronal firing rates appear to cause the preferential release of one or another of these substances. Most of the neuropeptides exert their postsynaptic effects through the G-protein transduction system, which uses adenyl cyclase or phospholipase C as an intermediary.
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The end-plate potential recorded after the spike has been blocked with curare. Acetylcholine acts to open the ionic channels in the postsynaptic membrane for only msec; the remainder of the end-plate potential is simply due to the passive properties of the muscle membrane.
After msec, the acetylcholine is removed from the receptor and hydrolyzed by the enzyme acetylcholinesterase , which is found on the postsynaptic membrane mainly in the region of the synaptic cleft.
Acetylcholinesterase is capable of hydrolyzing about 10 acetylcholine molecules per msec. Therefore, most of the transmitter substance is hydrolyzed, and the products are taken up again by the motoneuron terminal, but some of the acetylcholine escapes from the cleft and is carried away by the blood.
There is no danger that this escaped transmitter can re-excite the muscle because it is only effective in changing the membrane potential when applied to the membrane within the cleft, i. Within the motoneuron terminals, acetylcholine is stored in the synaptic vesicles, each vesicle containing about 10, molecules of acetylcholine.
Because the transmitter substance is stored in this fashion and because the entire content of a vesicle is released or none of it is released, it is reasonable to assume that the end-plate potentials must be made up of some multiple of the potential change caused by a single vesicle's contents. Actually, when recordings are made from a nerve-muscle preparation Fig. These have a time-course and configuration reminiscent of the end-plate potential, and they are termed miniature endplate potentials or MEPPs.
Pharmacologically and physiologically, it has been demonstrated that MEPPs have the same properties as the end-plate potential and that they are caused by spontaneous release of small quantities of acetylcholine. MEPPs tend to have the same amplitude or multiples of their smallest amplitude, so it is surmised that they are caused by release of nearly equal-sized packets of acetylcholine, called quanta.
It seems reasonable to assume that a quantum is the amount of transmitter in a single vesicle. It also seems reasonable that the end-plate potential is always composed of integral multiples of a MEPP. MEPPs occur spontaneously at irregular intervals with a low rate of occurrence at the resting end-plate. The motoneuron spike increases the rate of occurrence of MEPPs for a short time, msec, during which , quanta, depending upon the particular nerve-muscle preparation, are released.
The potential for change in the membrane potential of the muscle is enormous and therefore always more than enough to cause a spike in normal, healthy muscle. Because the process of transmission at the neuromuscular junction contains so many different steps, the possibilities for interference with the process are numerous.
Curare has already been mentioned as a blocker; curare competes with acetylcholine for the receptor sites, but is incapable of activating them. Other competitive blockers, such as decamethonium or succinylcholine, not only compete, but activate the receptor. Their paralyzing effect is due to the tenacity with which they bind the receptor and the difficulty with which they are removed from the receptor and hydrolyzed.
The toxin of botulinus bacteria, found in some spoiled food, is an extremely powerful neuromuscular blocker that works by preventing the release of the transmitter substance from the motoneuron terminals. Neuromuscular blocks can also be created by interfering with the action of the ACh-degrading enzyme acetylcholinesterase.
Cholinesterase inhibitors, such as neostigmine, block the removal and hydrolyzation of acetylcholine; thus, the muscle membrane stays hypopolarized for too long a period and the muscle cannot relax. This is the principle of action of many insecticides and nerve gases. Prolonged hypopolarizations lead to convulsions, then to paralysis and death, usually caused by paralysis of the diaphragm. The disease myasthenia gravis is characterized by muscle weakness after repeated activation of the neuromuscular junction, but not for a single activation.
Patients typically are strong in the morning, but become progressively weaker as the day goes on. The problem with the myasthenic appears to be threefold: With repeated activation of the synapse, the vesicular stores of acetylcholine are depleted, not replenished as they normally would be, and after a while the junction fails to transmit. In addition, the reduction in the number of receptors means that less of the acetylcholine available can be bound.
Administration of anticholinesterase drugs like neostigmine is sometime effective in treatment of myasthenia, probably because they make the acetylcholine remain in the cleft longer, increasing the likelihood that it will bind to a receptor and activate the muscle. The surface of a motoneuron soma studded with boutons terminaux. Amsterdam, Elsevier, Synaptic transmission between neurons. Spatial and temporal summation of EPSPs. EPSPs elicited by stimulation of two fibers afferent to a motoneuron both separately and simultaneously.
Notice the algebraic summation. EPSPs elicitied by a single stimulus to a fiber afferent to a motoneuron and two stimuli applied in rapid succession 2 msec apart. Like all generator potentials, EPSPs can show temporal summation. If the same afferent axon is stimulated twice in rapid succession, the response to the first stimulus is not yet over before the response to the second begins. The changes in potential again sum, but because they do not start at exactly the same time 2 msec apart , the sum is a bit irregular in shape Fig.
This is an example of temporal summation. The membrane potential can be brought to firing level by summation, spatial or temporal or both. Any number of EPSPs, from a variety of types of presynaptic neurons, can be summed by a single postsynaptic cell. Synapses that require a lot of summation to reach firing level are called integrative synapses , and they make up the bulk of the synapses in the nervous system. A few synapses require only one presynaptic action potential to bring the postsynaptic membrane to critical firing level, and these are called obligatory synapses.
An example of an obligatory synapse is the neuromuscular junction. A single action potential in a single alpha-motoneuron causes a postsynaptic action potential in every extrafusal muscle fiber in its motor unit a motoneuron plus all the muscle fibers it innervates is a motor unit.
Generation of the action potentials in the alpha-motoneurons themselves requires considerable summation, and therefore synapses on motoneuron somata or dendrites are integrative. Not all neurons behave exactly like motoneurons, but most use this same basic mechanism for transmission at chemical synaptic junctions with other cells. An IPSP elicited by a single stimulus applied to a peripheral nerve at increasing strengths from top to bottom. The IPSP, on the other hand, is produced by increased permeability of the membrane to chloride or potassium or both.
If V r is less negative than V Cl - , then the driving force on chloride will move it inward, creating an outward current. Under this circumstance, an increase in chloride conductance will hyperpolarize the membrane. On the other hand, if V r is more negative than V Cl - , then the driving force on chloride will move it outward, creating an inward current. Under this circumstance, an increase in chloride conductance will actually hypopolarize the cell.
Chloride and potassium are nearly in electrochemical equilibrium, and therefore their driving forces are small, but then the amplitude of the IPSP is also small. The EPSP by itself. The IPSP by itself. A much larger EPSP by itself. It is important that the inhibitory effect of the IPSP is not due simply to the hyperpolarization, driving the membrane away from the critical firing level, but also includes another process.
This is shown in Figure If the EPSP and the IPSP are initiated at the same time, the resulting change in potential is a small hyperpolarization as shown in C, not the small hypopolarization that would be expected if there were algebraic summation. The IPSP inhibits both by virtue of the decreased membrane resistance and the hyperpolarization. The hyperpolarization forces a greater amount of hypopolarization to achieve critical firing level, and the decreased membrane resistance reduces the size of the EPSP.
For this reason, inhibition always makes itself felt. Equal excitatory and inhibitory presynaptic inputs to a cell always result in inhibition of its discharge. And it is for this reason that increasing Cl - conductance inhibits even though Cl - is in electrochemical equilibrium and changing it conductance produces no voltage change in the cell. Current flow at synapses. Excitatory and inhibitory synapses are indicated on the soma and proximal dendrites and currents initiated at each, flowing through the possynaptic membrane and the region of the axon hillock, where the spike is thought to be initiated.
The postsynaptic membranes at all synapses are electrically inexcitable; the action potential is initiated somewhere else on the membrane. Most people think that the spike in most neurons is initiated in the region where the axon is connected to the soma, the axon hillock.
The axon hillock is thought to have an electrical threshold about half that of the soma and dendrites, so that the spike is initiated there first. Figure shows a drawing of the neuron showing the axon hillock, synaptic junctions on the soma and dendrites, and the currents that flow when the synapses are active.
This means that, for synapses producing equal changes in membrane potential at the synapse, the ones closer to the hillock have a greater influence on the firing of the cell. However, synapses on dendrites tend to generate particularly large EPSPs, somewhat offsetting their greater distance.
Inhibitory synapses, synapses that produce IPSPs, also tend to be located closer than excitatory synapses to the axon hillock the spike-generating region. This arrangement may also add to the great influence of IPSPs on the neuron membrane. The firing pattern of the neuron is completely determined by the sum of its synaptic bombardment, both excitatory and inhibitory.
This is especially important in cells with integrative synapses. It was pointed out in the earlier discussion of generator potentials that there is a linear relationship between generator potential amplitude and the frequency of discharge in the receptor or its nerve. The EPSP is a generator potential, and, like any good generator potential, its amplitude is related to discharge frequency in a linear way.
As a result, the firing frequency increases or decreases. Figure shows a hypothetical arrangement of synapses on a cell and some different configurations of synaptic potentials at the axon hillock A 5 and the resulting patterns of discharge in the axon hillock B. Shown are two excitatory synapses, one on the soma and one on a dendrite, and one inhibitory synapse on the soma. Each pattern in A was generated by some combination of inputs over the three synapses indicated by the letters: The same synapses are involved in generating each pattern; only the order and timing are changed.
Even small changes result in noticeably different patterns of spike discharges, with great consequences for behavior. Inset shows a neuron with three synaptic junctions--two on the soma and one on a proximal dendrite. Two of the synapses are excitatory; one is inhibitory. Transmembrane potential recorded with the micropipette, with different temporal arrangements of a single postsynaptic potential at each synapse indicated by letters under trace.
The spike trains that would be recorded from the axon of the cell as generated by the synaptic potential patterns in A. If the precise timing required to produce spatial and temporal summation is altered, the precise firing patterns of interneurons and motoneurons required to produce even the simplest of movements are no longer possible.
In fact, the real impact of certain demyelinating diseases such as multiple sclerosis is not due to destruction of neurons or even blockage of conduction; they still conduct at least in the early stages of the disease , although at reduced velocities after the myelin is removed. The slowed conduction in a demyelinating disease means that some impulses do not arrive on time at synapses on motoneurons.
Considering the time constant of an EPSP, a slowing of conduction that produces even a 0. The timing of the arrival of impulses is also important in sensory events.
Humans use small differences in the time of arrival of a sound at the two ears to localize the source of sounds with low frequencies. This difference in arrival time can be as little as 30 sec. Clearly, very close timing of impulses is essential to this behavior. In some cases, the postsynaptic potential elicited by a given transmitter substance can be altered by, or contingent upon, the postsynaptic action of a neuromodulator. For example, a brief exposure to dopamine released synaptically into sympathetic ganglia enhances the muscarinic hypopolarizations induced by acetylcholine for hours, even though the dopamine causes no change in the membrane potential or resistance of the postsynaptic cell.
Similar effects of dopamine have also been described in the caudate nucleus and hippocampus. A shorter potentiation of both excitatory and inhibitory responses of Purkinje cells in the cerebellar cortex is induced by norepinephrine released by axons originating in the locus ceruleus.