Since an IPSP hyperpolarizes the membrane, it inhibits action potentials. Remember that a neuron synapses with many other neurons. So a postsynaptic neuron can receive signals from many presynaptic neurons simultaneously.
Whether or not the postsynaptic cell has an action potential depends on the summation the additive effect of all the incoming signals.
The net effect of all the local potentials on the trigger zone determines whether or not there is an action potential in the postsynaptic cell. There are two different ways that local potentials can sum to excite the postsynaptic cell to have an action potential. Temporal summation occurs when successive EPSPs at a single synapse occur in rapid succession.
The successive potentials occur before the previous ones die out producing an increasing membrane depolarization. Temporal summation occurs when one synapse stimulates the postsynaptic cell very quickly and the EPSPs produced in the postsynaptic cell piggyback on each other causing an increasing level of depolarization.
The effect of temporal summation on membrane voltage at the trigger zone. The threshold voltage is attained and the postsynaptic cell fires an action potential. Summation can also occur when multiple presynaptic neurons stimulate the postsynaptic neuron at the same time spatial summation.
Each individual synapse lets in a limited number of ions and alters the membrane potential a little. The collective effect of all the synapses allows in enough ions to reach the threshold potential and an action potential is triggered.
Spatial summation occurs when the collective effect of multiple synapses depolarizes the postsynaptic neuron to threshold resulting in an action potential. Neurotransmitters are organic molecules that allow neurons to communicate with each other and with target cells. Neurotransmitters fall into four classes based on their chemical makeup. Acetylcholine ACh is a small molecule formed from acetate and choline. It is in a class by itself.
Acetylcholine is the sole neurotransmitter used at the neuromuscular junction and is also the neurotransmitters used by the parasympathetic nervous system. Some amino acids act as neurotransmitters. Glutamate glutamic acid and aspartate are excitatory neurotransmitters found in the brain and spinal cord, respectively. Biogenic amines monoamines are formed from amino acids from which the carboxyl terminus is removed. Three of the biogenic amines, called the catecholamines, are grouped together as they are all derived from the same amino acid, L-tyrosine.
The catecholamines include: norepinephrine noradrenalin , epinephrine adrenalin and dopamine dopamine can also be made from phenylalanine. Norepinephrine NE is the neurotransmitter of the sympathetic nervous system your fight or flight response. Epinephrine E has similar effects to NE, but is less abundant.
Dopamine is best known for its role in motor inhibition. Loss of dopamine producing neurons in Parkinson disease leads to dyskinesias movement disorders. Catecholamines bind to adrenergic receptors. Other biogenic amines include serotonin and histamine. The structures of the biogenic amine neurotransmitters. Neuropeptides are small proteins that function as neurotransmitters. They are the largest neurotransmitters and can range from just a couple of amino acids to as many as Examples of neuropeptide neurotransmitters.
Privacy Policy. These synapse types have different molecular compositions and physiological properties: a single action potential generates a 1 mV potential from type 1 a weak synapse , 2 mV from type 2 a medium strength synapse and 3 mV from type 3 a strong synapse. There is a non-random spatial organization synaptome architecture to the heterogeneous population, where the top two layers are type 2 synapses, the third layer is type 3 and the fourth layer is type 1 Figure 2B.
When these two populations are stimulated with a single action potential, there are distinct spatial maps of synaptic responses observable at single-synapse resolution. In other words, electrophysiological methods that record population measurements are blinded to the diversity of synapses and their spatial organization. Figure 2. Populations of A homogeneous and B heterogeneous synapses can show the same overall response. The key shows three synapse types and their strength.
Next we will consider how population recordings could confuse the interpretation of synaptic plasticity in heterogeneous populations of synapses Figure 3. Here we will contrast two stimulation protocols: one that results in long-term potentiation LTP and another that results in long-term depression LTD.
However, unlike the homogeneous population where all the synapses either strengthen or weaken, the heterogeneous populations show physiological diversity at the single-synapse level: some synapses strengthen and others weaken. If the specific synapses or subsets within each population were to have distinct physiological outputs for example, because of their location within the dendritic tree then the population recording could not be relied upon to inform us if their output was increased or decreased in either the LTP or LTD experiment.
Figure 3. Although both homogeneous and heterogeneous populations show LTP and LTD, only some synapses in the heterogeneous populations reflect the population measure and subpopulations of synapses can show opposite phenotypes i. The failure of population recordings to discriminate spatial effects of heterogeneous synapse populations has important implications for those experiments that attempt to correlate physiological and behavioral properties.
For the purposes of this discussion, we will assume that a subset of synapses within the population drive a circuit that controls the behavior behavior-relevant synapses. An increase in synaptic strength recorded in the whole population of synapses LTP would not necessarily correlate with an increase in synaptic strength in the behavior-relevant synapses and so there would not be a correlation between LTP and learning.
Thus, if we assume that LTP is the causal mechanism of learning Bliss and Collingridge, , then synapse diversity could be invoked to explain why dissociations between the direction or strength of change in LTP and learning do not necessarily refute that model. If we do not start with the a priori assumption that LTP is the mechanism of learning, then population-averaging recordings of synapses cannot be used to support the model because it cannot be safely assumed that all synapses are functioning in the same way, as shown in Figure 3B.
Therefore, experiments that do not resolve the physiological properties of individual synapses and rely on population measurements cannot be used to support or rebut the LTP model of learning.
A substantial body of literature describes changes in LTP and LTD during the postnatal developmental period and has suggested that these changes are important for learning in critical periods Fox, ; Feldman et al. Our recent study of the lifespan synaptome architecture shows a dramatic increase in excitatory synapse diversity during the postnatal developmental period, with every brain region undergoing major compositional changes in heterogeneous synapses Cizeron et al.
Thus, although the electrophysiological studies have been interpreted as changes in long-term synaptic strength through synaptic plasticity of existing synapses, a radical suggestion, which remains formally possible, is that there could be circumstances where there are no changes in long-term synapse strength mediated by plasticity but changes in the composition of synapse populations.
Nevertheless, stimulation of single presynaptic terminals can induce short-term plasticity indicating that at least this form of plasticity occurs at single synapses Vandael et al. Untangling the relative contribution of synaptic plasticity and changing populations of synapses to the long-term changes in synaptic strength will require physiological and molecular studies of synapses at single-synapse resolution.
It has long been known that drugs bind to proteins, and because synapses contain different proteins then drugs will target different synapses.
This logic has been at the heart of the majority of neuropharmacological therapies and interventions that target neurotransmitter systems. Here we will illustrate how synapse diversity can confound the interpretation of pharmacological experiments.
For simplicity, we will assume the standard position in the literature — that patterns of neural activity can activate the NMDAR and postsynaptic signaling pathways lead to strengthening of synapses Nicoll, Figure 4.
The differing molecular composition of individual synapses confounds the interpretation of signaling mechanisms. After stimulation Stim 1 , LTP is induced in all the homogeneous synapses A1 but in only half the heterogeneous synapse populations B1 even though LTP is measured in the whole population. However, there are synaptic physiological changes in the heterogeneous population that remain undetected B2. Both homogeneous and heterogeneous populations show no overall change in synaptic strength; in other words, LTP is blocked.
These simulations show that in an experiment in which there is diversity in the expression of the NMDAR and downstream signaling molecules, a misleading interpretation can be drawn of the synaptic changes within the population. As noted above, if these subpopulations are of differing relevance to behavioral outputs then the population measures would give a misleading interpretation of both the electrophysiological and pharmacological data.
The scenarios we portray are not unrealistic as studies of spike timing-dependent plasticity show that a given pattern of pre- and post-synaptic activation induces LTP at some synapses and induces LTD at other synapses Brzosko et al. In addition to considering the action of drugs that target neurotransmitters these principles apply to signaling and metabolic enzymes, which are known to have differential distributions Roy et al.
If synapses showed different rates of protein synthesis then protein synthesis inhibitors would exert different phenotypes on individual synapses. There are well-documented examples of dissociations between protein synthesis and long-term memory, which remain unexplained Routtenberg and Rekart, ; Gold, , potentially because of synapse diversity. Genetic perturbations e. Broadly speaking, synaptome reprograming changes one heterogeneous population of synapses into a different population Figure 5.
We will consider two versions of synaptic reprograming that occur with gene mutations: i where the spatial location of the different synapses has changed Figure 5 , mutation 1 ; and ii where the numbers of synapse types and their spatial location have changed Figure 5 , mutation 2. Figure 5. Synaptome reprograming by gene mutations alters the spatial distribution of heterogeneous synapses. Mutation 2, however, has altered the representation of synapse types more type 1 and fewer type 2 and an LTP-inducing stimulus shows less LTP than the wild type.
After an LTP-inducing stimulation, the response of mutation 1 is the same as wild type, but the mutant synaptome produces different outputs from those synapses located in rows 2 and 4. If these were behavior-relevant synapses, then this would produce behavioral differences to the wild type without an apparent difference in LTP. The response of mutation 2 is a different spatial output to the wild type and mutation 1 and an overall lower LTP.
The behavioral output will depend on the relative importance of synapses in different locations. Together, these examples illustrate how genetic mutations could produce a change in LTP and have any number of effects increase, decrease or no change on behavior. These simulations have implications for the interpretation of population recording in mutant organisms. In the presence of synaptic diversity it is not possible to conclude the physiological properties of individual synapses or the potential contribution to a behavioral output without knowing the physiological changes in each synapse and the spatial location of the synapse.
With synaptome reprograming, the spatial reorganization of synapse types complicates the interpretation of basal physiological differences between wild type and mutant, and of differences that arise after a stimulation protocol that induces LTP. The vast majority of electrophysiological studies of synaptic function employ methods that record from populations of synapses. Data from these experiments have been highly influential; for example, they have been used to support the hypothesis that an increase in stable synaptic strength can account for learning and for how behaviors change during development.
These models are based on the assumption that the synapses are homogeneous and therefore the population measure can be extrapolated to reflect the physiology of the individual synapses. However, in the presence of synapse diversity, the population measure does not accurately inform on the physiological properties of individual synapses.
As we have argued, there can be a dissociation between the population measure and the changes in subsets of synapses. Synapse diversity interferes in many different ways with the interpretation of electrophysiological experiments that record populations of synapses.
Phenotypic dissociations between electrophysiology and behavior using pharmacological and genetic approaches are confounded. Indeed, there have been many examples where LTP and learning have been dissociated with pharmacological and genetic approaches. These dissociations could be explained by synapse diversity and synaptome reprograming. Although synapse diversity and synaptome reprograming could be used to dismiss a dissociation, we need to recognize that the null hypothesis itself that LTP is the causal mechanism of learning is also subject to the same confound because the experiments that have shown the correlation between synapse strength and learning are themselves based on population measurements of synapse physiology.
An important area of molecular neuroscience has been the dissection of signaling pathways from neurotransmitter receptors. These experiments have almost universally used synapse population measures e. However, the molecular targets of these drugs and the proteins comprising the signaling pathways can differ between synapses, and the physiological outputs could therefore represent changes in the relative contributions of different synapse types rather than the efficacy of the putative pathway.
This problem has previously been described in the context of cellular heterogeneity Altschuler and Wu, Synapse electrophysiology is not the only area of synaptic biology that is bedeviled by synapse diversity.
Many biochemical studies involve extracting proteins from populations of synapses e. It is also important to recognize that homogenous synapses can have differential physiological outputs depending on their spatial location in the dendritic tree Spruston, When considering the physiological importance of synapses, it is therefore necessary to consider the spatial location and the molecular, morphological and functional characteristics of each synapse.
This underlines the conceptual and practical importance of the synaptome architecture Grant, b ; Zhu et al. The first synaptome maps that describe the synaptome architecture of the mouse and human brain are now emerging Zhu et al. Once a nerve impulse has triggered the release of neurotransmitters, these chemical messengers cross the tiny synaptic gap and are taken up by receptors on the surface of the next cell.
These receptors act much like a lock, while the neurotransmitters function much like keys. Neurotransmitters may excite or inhibit the neuron they bind to. Think of the nerve signal like the electrical current, and the neurons like wires. Synapses would be the outlets or junction boxes that connect the current to a lamp or other electrical appliance of your choosing , allowing the lamp to light.
Synapses are composed of three main parts:. An electrical impulse travels down the axon of a neuron and then triggers the release of tiny vesicles containing neurotransmitters.
These vesicles will then bind to the membrane of the presynaptic cell, releasing the neurotransmitters into the synapse. These chemical messengers cross the synaptic cleft and connect with receptor sites in the next nerve cell, triggering an electrical impulse known as an action potential.
There are two main types of synapses:. In a chemical synapse, the electrical activity in the presynaptic neuron triggers the release of chemical messengers, the neurotransmitters. The neurotransmitters diffuse across the synapse and bind to the specialized receptors of the postsynaptic cell. The neurotransmitter then either excites or inhibits the postsynaptic neuron. Excitation leads to the firing of an action potential while inhibition prevents the propagation of a signal.
In electrical synapses, two neurons are connected by specialized channels known as gap junctions. Electrical synapses allow electrical signals to travel quickly from the presynaptic cell to the postsynaptic cell, rapidly speeding up the transfer of signals. The special protein channels that connect the two cells make it possible for the positive current from the presynaptic neuron to flow directly into the postsynaptic cell.
The gap between electrical synapses is much smaller than that of a chemical synapse about 3. Electrical synapses transfer signals much faster than chemical synapses.
While the speed of transmission in chemical synapses can take up to several milliseconds, the transmission at electrical synapses is nearly instantaneous. While electrical synapses have the advantage of speed, the strength of a signal diminishes as it travels from one cell to the next. Because of this loss of signal strength, it requires a very large presynaptic neuron to influence much smaller postsynaptic neurons.
Chemical synapses may be slower, but they can transmit a message without any loss in signal strength. Very small presynaptic neurons are also able to influence even very large postsynaptic cells. Where chemical synapses can be excitatory or inhibitory, electrical synapses are excitatory only. Sign up for our Health Tip of the Day newsletter, and receive daily tips that will help you live your healthiest life. Lodish HF.
0コメント