Neurons are continuously receiving from thousands of other neurons around it. However, whether these inputs are able to elicit an action potential or not depends on the summation of these inputs. Summation can be defined as a process by which the excitatory and inhibitory signals together are able to generate an action potential or not.
There are two types of summations, these are the temporal and spatial summations, respectively. Spatial summations can be defined as signals coming from multiple simultaneous inputs. Temporal summation on the other hand comes from repeated inputs. Essentially to achieve an action potential, the threshold voltage must be reached. This can be determined by adding up the individual inputs from temporal and spatial summation.
There are two types of neurotransmitters released from presynaptic neurons. Depolarization is caused by excitatory neurotransmitters, this is called an excitatory postsynaptic potential (EPSP). Inhibitory neurotransmitters cause hyperpolarization, in other words an inhibitory postsynaptic potential (IPSP). Neurons are able to affect one another in a number of ways. They are able cause excitation, inhibition and may bias each other’s excitability.
Defacilitation is the removal of excitatory inputs which can facilitate a pathway. Disinhibition on the other hand is the inhibitory input removal.
Multiple source inputs on a neuron can be summated spatially, however the inputs must be closely spaced so that none of the early inputs decay. If a neuron is receiving multiple inputs from a single source in the required close time interval so that no input is decayed, then these inputs may summate temporally.
Another very important factor in determining whether the threshold potential is reached and an action potential is achieved or not is the distance between the synapse and the neuronal cell body. The closer the distance between the synapse and cell body, the greater the summation and the more likely it is to elicit an action potential.
As we know the means of travel for a postsynaptic neuron is a dendrite. These dendrites have few voltage gated ion channels. Hence, on reaching the neuronal cell body, the postsynaptic potential attenuates. This neuronal cell body summates these incoming potentials. An action potential is then elicited on transmission of the net potential to the axon hillock.
When inputs from multiple neurons trigger an action potential, this is called as spatial summation. These potentials are most commonly from dendrites, we add these inputs together to get the spatial summation.
The greater the number of excitatory post synaptic potentials, the greater the chances of the potential achieving the threshold potential to elicit an action potential. Similarly, the greater the number of inhibitory postsynaptic potentials, the lesser the chances of reaching the threshold potential to generate an action potential.
The chances of eliciting an action potential are also significantly influenced by how close the dendritic input is to the axon hillock. The closer the dendritic input is to the axon hillock, the more likely it is to cause an action potential. Shunting of an excitatory postsynaptic potential is the is the nullification of an excitatory inputs by the spatial summation of inhibitory inputs.
When a large amount of presynaptic neuron action potentials triggers postsynaptic action potentials that summate with one another, this is called as temporal summation.
In this case, the interval between action potentials is less than the postsynaptic action potential duration. The summation may be increased if the cell membrane time constant is long enough. When the next postsynaptic potential starts, the amplitude of the previous postsynaptic potential will summate with it producing a greater potential increasing the likelihood of reaching the threshold potential.
The postsynaptic cells contain ion channels, these ion channels may open or close depending on which neurotransmitter bind to the receptors. The opening/closing of these channels creates a postsynaptic potential. There are 2 types of postsynaptic potentials. An excitatory postsynaptic potential is that which increases the chances of initiating an action potential. Similarly inhibitory postsynaptic potentials decrease the chances of an action potential being initiated.
Excitatory neurotransmitters (Glutamate)
One prime example of an excitatory neurotransmitter is glutamate. This glutamate binds to AMPA receptors on the postsynaptic membrane. This binding causes a sodium cation influx. This sodium influx causes a depolarization. This is called as the excitatory postsynaptic potential (EPSP). It is essential to note that for the EPSP summation to reach the threshold potential, a large number of these inputs are required. The effects of neurotransmitters last much longer than that of presynaptic impulses.
The difference between excitatory postsynaptic potentials and action potentials is that excitatory postsynaptic potentials are able to summate its inputs producing a graded response as opposed to the all or nothing response in which the threshold potential may be reached stimulating an action potential or it may not be reached at all.
Inhibitory neurotransmitters (GABA)
GABA is the main neurotransmitter involved in inhibitory postsynaptic potentials (IPSP). On binding to postsynaptic neuron receptors GABA opens specific ion channels which are different from those opened in EPSP by excitatory neurotransmitters like Glutamate. These channels allow an influx of negatively charged anions or an efflux of positively charged cations. The anion in this case is chloride ions. The effluxed cations are potassium ions. Both ions have the same effect in lowering membrane potential causing hyperpolarization of the postsynaptic neuron.
Summation of these IPSPs and the drop in membrane voltage will deviate away from the threshold potential inhibiting an action potential. However these IPSPs and EPSPs may be occurring at the same time, hence the postsynaptic neuron may be receiving excitatory signals from glutamate and inhibitory signals from GABA. The goal of inhibitory glutamate is to lower membrane potential away from the threshold potential by hyperpolarization.
Algebraic processing of EPSPs and IPSPs
In any neuron at any point in time, it will be receiving numerous EPSP and IPSP inputs simultaneously. To determine the output whether the threshold potential will be reached and an action potential will be elicited or not, the algebraic processing of these EPSPs and IPSPs must be taken. These neurons will be receiving numerous inputs whether it be from multiple neurons (spatial summation) or multiple inputs from one single neuron (temporal summation).
This output depends on the number of each type of neurotransmitter whether it be excitatory neurotransmitters like glutamate which cause sodium ion influx through sodium ion channels or inhibitory neurotransmitters like GABA which cause a chloride ion influx or potassium ion influx through chloride or potassium ion channels respectively. This synapse can referred to as the decision point where algebraic processing of these IPSPs and EPSPs determines the output.
The part of the cell body of a neuron that connects to the axon is called the axon hillock. It has a sparse distribution of Nissl substance. We are able to identify it by light microscopy. As this axon hillock connects the axon and soma of the neuron, it is the final region of the soma where summation of membrane potentials from synaptic inputs occurs. This summation is then transmitted to the axon.
Although in the past, many believed the axon hillock to be the trigger zone where action potentials are initiated, it is now believed that the initial segment between initial unmyelinated axon segment and the axon hillock peak is where the action potential is initiated. The positive point of the axon where the action potential is started varies from cell to cell.
Hormonal stimulation and neurotransmitter second messenger effects may also change this positive point. Localization of membrane potentials to the somal or axonal part of the cell may be achieved by delineation of distinct membrane domains between the axon and cell body. This can be achieved by the axon hillock.
Often times in a neuron, the excitatory postsynaptic and inhibitory postsynaptic potentials in a dendrite are very close to one another. This is called as shunting. In addition to dendrites, shunting may also occur in the soma of a cell.
Temporal summation would tell us to summate these excitatory postsynaptic and inhibitory postsynaptic potentials in order to determine the resulting output whether the threshold potential is reached and an action potential is initiated or not. However in the case of this sequence of events occurring in the soma of a call, the cell resistance is altered by the inhibitory input. The cell begins to leak, this will create a shunt as opposed to getting rid of the excitatory input’s effect.
When discussing nociceptive stimulation, temporal summation is repetitive painful stimuli integration. Spatial summation on the other hand is nociceptive input integration from large areas. Many chronic diseases have symptoms of long durations of pain which are widespread. Hence both temporal and spatial nociceptive summations are found in chronic diseases. Pressure stimulation experiments provide proof of the fact that temporal summation of nociceptive inputs is facilitated through spatial summation. Hence the best course of action in treatment of chronic pain is to direct the treatment towards both spatial and temporal summation of pain.
Most experimentations of spatial summation are tested on optical and sensory neurons, the reason for this being that they have a constant range of frequency of excitatory and inhibitory neurons. Postsynaptic potential attenuation of neuron cell bodies and dendrites is large focus of neural summation in recent day studies. Due to the fact that the response of these interactions is less than the sum of the individual responses, these responses are described as nonlinear. Shunting is a common cause on this effect. Shunting is decreased excitatory postsynaptic potential conductance.
Naoki Kogo and Michael Ariel were able to experiment on turtle basal optic nucleus, from this they were able to draw information on shunting inhibition. According to their work, EPSP and IPSP spatial summation caused excitatory response attenuation during the inhibitory response. It was also noticed that after attenuation there was augmentation of the excitatory response. The control for this experiment was testing for attenuation when a hyperpolarization current activated these voltage sensitive channels. It was concluded that attenuation is caused by synaptic receptor channel opening and not hyperpolarization.
At any given time, a neuron will be receiving multiple inputs from multiple different neurons.
These inputs may be excitatory or inhibitory, however, to determine whether the threshold potential will be reached and an action potential will be elicited or not, a number of factors must be looked at.
Different neurotransmitters have different effects, excitatory neurotransmitter like glutamate cause opening of sodium ion channels causing sodium ion influx raising the membrane potential. Inhibitory neurotransmitters like GABA can open chloride ion channels causing chloride ion influx or it may open potassium ion channels causing potassium ion efflux.
Both of these effects lower the membrane potential deviating it away from the threshold voltage decreasing chances of initiating an action potential.
Another factor which increases the chances of initiating an action potential is how close the dendritic input is to the axon hillock, the closer the higher the chances on an action potential being initiated. An axon hillock is part of the soma of a neuron that connects it to the axon.
Excitatory neurotransmitters increase the chances of depolarization, the change in the membrane voltage is called as an excitatory postsynaptic potential (EPSP). Inhibitory neurotransmitters increase the chances of hyperpolarization, this change in the membrane potential called as an inhibitory postsynaptic potential (IPSP).
Whether the threshold voltage will be reached, and an action potential will be initiated or not, depends on the algebraic summation of the individual inputs. There are two types of summation.
Summation of multiple inputs from multiple different presynaptic neurons triggering an action potential is called as spatial summation. A high frequency of inputs from one presynaptic neuron summated to produce an action potential is called as temporal summation. This postsynaptic potential duration is longer than the duration between the respective action potentials.
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