Synapse

“ The difference between the two autonomic nervous systems and the central (cerebro-spinal) system is that, in the former, the nerve fibers never proceed, as ordinarily, directly from the nerve center to the organ controlled, but pass, as neurons, from the gray substance to a ganglion in which they encounter a break or synapse (separating surface) , on the other side of which a similar post-ganglionic neuron proceeds to the organ controlled. The synapse, a term first proposed by Sir Michael Foster, has been likened to a switch over which the nervous impulse jumps to proceed on its way. ”

“ Every time it passes, it exercises the end-brush and dendrites at the synapse (for the "passage of a nerve current" really means activity on the part of the neurones through which it passes) , and the after-effect of this exercise is growth of the exercised parts, and consequent improvement of the synapse as a linkage between one neurone and the other. Repeated exercise may probably bring a synapse from a very loose condition to a state of close interweaving and excellent power of transmitting the nerve current. ”

“ It is thought that the most important changes in the nervous system do not occur within the individual neurones, but at the points where they join with each other. This point of connection is called the synapse and although we do not understand its exact nature, it may well be pictured as a valve that governs the passage of the nervous current from neurone to neurone. At time of birth, most of the valves are closed. Only a few are open, mainly those connected with the vegetative processes such as breathing and digestion. ”

“ The more a synapse is used, the better synapse it becomes, and the better linkage it provides between some stimulus and some response. The cortex is the place where linkages are made in the process of learning, and it is there also that forgetting, or atrophy, takes place through disuse. Exercise makes a synapse closer, disuse lets it relapse into a loose and poorly conducting state. ”

“ In terms of functional operation, we can think of the synapse as a transducer. The input to this transducer is a spike or series of spikes in the presynaptic axon. The output is an accumulative, long-lasting potential which in some way (perhaps not uniquely) represents the pattern of presynaptic spikes. The pacemaker appears to perform the function of a clock, producing periodic spikes or spike bursts or producing periodic changes in the over-all excitability of the neuron. The graded-response regions appear to act as nonlinear amplifiers and, occasionally, spike initiators. ”

“ The vocal movement of saying the name is made in response to the auditory stimulus of hearing the name, but when the neurone in the "speech center" is thus made active, it takes up current also from the axon that reaches it from the visual center, even though the synapse between this axon and the speech neurone is far from close. This particular synapse between the visual and the speech centers, being thus exercised, is left in an improved condition. Each neurone in the diagram represents hundreds in the brain, for brain activities are carried on by companies and regiments of neurones. ”

“ London, 1903) and McDougal ("Synapse Theory of Fatigue," Brain, 1910) has deservedly attracted wide attention. They contend that all the phenomena can be more simply explained without postulating the movement required for the Duval Theory or the glial activity of Ramon y Cajal's hypothesis. They consider that each nerve cell has, as it were, a certain potential energy which it sends forth in nerve impulses. These are transferred from neuron to neuron through the synapse. ”

“ Close connection might mean protoplasmic union, or proximity of the neurones in space, or a greater permeability of a membrane, or a lowered electrical resistance, or a favorable chemical condition of some other sort. Let us call this undefined condition which parallels the strength of a connection between situation and response the intimacy of the synapse. Then the modifiability or connection changing of a neurone equals its power to alter the intimacy of its synapses. ”

“ At the present time, owing to the researches of Golgi, Ramón y Cajal, and others, the nervous system is considered to be composed of a number of separate nerve-units, called neurones, each neurone consisting of a nerve-cell with its various processes; one of these—the neuraxon—constitutes the nerve-fibre belonging to that nerve-cell, the other processes—the dendrites—establish communication with other neurones. The place where these processes come together is called a synapse, and the tangle of fine fibres formed at a number of synapses forms the 'neuropil.' ”

“ The strength of the communication at each synapse changes in response to neuronal activity—a process called synaptic plasticity—allowing networks of neurons to adapt and learn. How synaptic plasticity occurs is a major question in neurobiology. A central player in synaptic plasticity is an assembly of synaptic proteins called the NMDA receptor complex. Here, we discovered that the protein Neto1 is a component of the NMDA receptor complex. Neto1-deficient mice had a dramatic decrease in the number of NMDA receptors at synapses and consequently, synaptic plasticity and learning were impaired. ”

“ A—Diagram to illustrate neurons and their method of connection; a, axon; d, dendrite; s, synapse. To simplify the diagram the medullary sheathes of such fibers as would have them have been omitted. The arrows indicate the direction in which the impulse travels. The lower series shows diagrammatically how from the same neuron in the cortex two subordinate neurons may be affected, the one excited to cause contraction of a certain group of muscle fibers, the other inhibited so that the antagonistic fibers may relax and thus not hinder the movement of a given part. ”

“ Tracts of association are probably formed in definite lines through the nervous system, as during the life of a child repeated waves of sense impulses beat against and overcome resistances, and make smooth pathways here and there through the brain structure. Thus may be produced growth of axons in certain directions, and synapses of this cell with that. If the same stimulus be often repeated, the synapses between groups of cells may become permanent. A memory, a definite line of action which is manifested by a certain muscular response, may thus become structurally fixed. ”

“ Error bars are SEM. SN: sensory neuron, MN: Motor neuron. Having established that antisense oligonucleotides are able to knock down ApHTT mRNA levels in sensory neurons, we examined whether the down regulation of ApHTT mRNA by antisense oligonucleotides in the presynaptic sensory neurons affects basal synaptic transmission in the sensory-motor neuron synapse by measuring excitatory postsynaptic potentials (EPSPs) at 24 hours after oligonucleotides injection (50 ng/μl) to the presynaptic sensory neurons. ”

“ If the stimulus be not repeated, the synapses may be but temporary, and the memory fade as the group of cells is occupied by a new memory of some more potent sense stimulus. Many association tracts and synapses are laid down in the central nervous system when the child is born. ”

“ Each ganglion consists of ganglion-cells, nerve-fibres, and 'neuropil,' and, in addition, supporting cells of a neuroglial type. By means of the methylene blue method and the Golgi method, it is seen that the retinal end-cells, with their visual rods, are connected with the fibres of the optic nerve by means of a system of neurones, the synapses of which take place in and help to form the 'neuropil' of the various ganglia. Thus, an impulse in passing from the retina to the brain would ordinarily travel over five neurones, beginning with one of the first order and ending with one of the fifth. ”

“ Together, our results establish the principle that auxiliary proteins are required for the normal abundance of NMDAR subunits at synapses, and demonstrate that an inherited learning defect can be rescued pharmacologically, a finding with therapeutic implications for humans.==Abstract== Author Summary
The fundamental unit for information processing in the brain is the synapse, a highly specialized site of communication between the brain's multitude of individual neurons. ”

“ The human brain contains approximately 1010 neurons to which the neuron theory assigns the primary role in central nervous activity. These cells occupy, however, a relatively small fraction of the total volume. There are, for example, approximately 10 times that number of neuroglia, cells of relatively indeterminate function. Each neuron (consisting of cell body, dendrites and, sometimes, an axon) comes into close contact with the dendrites of other neurones at some thousands of places, these synapses and “ephapses” being spaced approximately 5μ apart (1) . ”

“ Now, perikarya and synapses are not present in the white matter of the central nervous organ, any more than they are in nerve-trunks. They are confined exclusively to those portions of the central organ which consist of grey matter (so called from its naked-eye appearance) . ”

“ The neural connections of the vestibular organ consist of numerous chains of neurons, reciprocally linked in many ways and having their synapses in various anatomical nuclei. All the chains work in intimate collaboration, and the final pattern of reflex responses is attributable largely to the highly complex integrating activity of the center. ”

“ This also illustrates how one nerve center influences another. (Figure text: white matter, gray matter, lung, respiratory center in the brain stem, diaphragm, motor center in cord for the diaphragm)
Very often, and possibly always, the reflex arc really consists of three neurones, a "central" neurone intervening between the sensory and motor neurones and being connected through synapses with each. The central neurone plays an important rôle in coördination. ”

“ Given that Neto1 is expressed in the CA1 region of the hippocampus (Figure 1C) , we studied synaptic transmission and plasticity at Schaffer collateral-CA1 synapses, which are widely used to investigate glutamatergic synaptic physiology [31] . We recorded field excitatory postsynaptic potentials (fEPSPs) in acute hippocampal slices from adult animals and used theta-burst pattern stimulation to induce long-term potentiation (tbLTP) , a robust form of NMDAR-dependent synaptic plasticity [32] . ”

“ The possibility of conduct or intelligence depends upon the connections at the synapses,—upon the possibility of the current affecting neurones in a certain definite way. The possession of an 'original nature,' then, means the possession, as a matter of inheritance, of certain connections between neurones, the possession of certain synapses which are in functional contact and across which a current may pass merely as a matter of structure. Just why certain synapses should be thus connected is the whole question of heredity. ”

“ It means that the synapses between stimulus and response are so improved, when traversed by nerve currents in the making of a reaction, that nerve currents can get across them more easily the next time. ”

“ Left: At wild-type synapses, during basal synaptic transmission, glutamate release activates AMPA receptors, causing a depolarization of the synaptic membrane. Right: During LTP induction, membrane depolarization provides a temporary relief of the magnesium ion blockade of NMDARs (primarily NR2A-NMDARs) , allowing sodium and calcium ions to enter through the receptor, which triggers events leading to LTP. (B) Left: At Neto1-null Schaffer collateral-CA1 synapses, basal synaptic transmission through AMPA receptors is unperturbed. ”

“ Each neuron does not extend to and from the brain and the periphery, but series of neurons connect the surface of the body with the brain. There is usually a group of neurons in the path from the surface to the brain cortex. The peripheral neuron for sensation runs from the surface of the body to the spinal cord, while for motion it runs in the opposite direction. There is a secondary neuron in each chain that runs up or down the spinal cord to and from the base of the brain. ”

“ The time course and magnitude of facilitation or antifacilitation may very well be important synaptic parameters. In addition, the postsynaptic membrane sometimes exhibits excitatory or inhibitory aftereffects (or both) on cessation of a volley of presynaptic spikes (2) , (7) ; and the time course and magnitude of the aftereffects may be important parameters. Clearly, even if one considers the synaptic potentials alone, he is faced with an impressive variety of responses. ”

“ These neurons are controlled for the most part by fibers from the bulb and spinal cord, and cannot for this reason be looked upon as forming an independent system. Their chief purpose seems to be that of spreading the influence of neurons from the central system over a wider area than they would otherwise reach. For example, a single neuron passing out from the spinal cord may, by terminating in a sympathetic ganglion, stimulate a large number of neurons, each of which will in turn stimulate the cells of muscles or of glands. ”

“ Although it can not be said at present that a synaptic nervous system is the peculiar possession of the vertebrates, there are two important features in which the central organs of these animals differ from those of the invertebrates. In the first place, the central organs of vertebrates exhibit a large prepondernace of long neurones over short ones, and in the second place, they show an enormous increase in the number of association neurones. ”