A central neuron receives input signals from ~10,000 synapses,

some excitatory in the form of EPSPs, and some inhibitory in

the form of IPSPs. Synaptic integration determines whether or
not the central neuron fires an action potential. This refers to the
way the many inputs from presynaptic neurons are summated
within the postsynaptic neuron to generate an action potential. In
this essay, I shall discuss the factors influencing synaptic
integration, namely
a) the type of input (excitatory or inhibitory)
b) spatial and temporal summation
c) localization of synapses
d) voltage-gated ion channels in the dendritic tree
Additionally, epiphatic interactions may influence the ability of
a neuron to fire an AP.
a) Type of input
i)
Excitatory
In the CNS, the main excitatory neurotransmitter is glutamate.
When an AP arrives at the presynaptic terminal, the resulting
depolarization causes voltage-gated calcium channels to open.
The subsequent rise in intracellular free calcium triggers the
fusion of synaptic vesicles containing glutamate to the
presynaptic membrane via SNARE proteins. The released
glutamate then diffuses across the cleft and bind to either ligandgated ion channels (AMPA & NMDA receptors) or metabotropic
receptors (mGluR1-mGluR5). Regardless of whichever receptor
is bound, the end result is the same, i.e. the postsynaptic
membrane is depolarized (by sodium and calcium influx), and
this EPSP travels towards the soma and axon hillock, making it
likelier for the neuron to fire an AP.
ii) Inhibitory
Much of the mechanisms by which an inhibitory signal is
tranduced, i.e. the calcium dependent exocytosis of
neurotransmitters are similar to that of in excitation. However,
instead of having glutamate, GABA and glycine are the main
neurotransmitters released by these inhibitory neurons. They
bind to metabotropic and ionotropic receptors on the

postsynaptic membrane, and cause a hyperpolarization (either

by potassium efflux or chloride influx). The IPSP, like the EPSP
travels towards the soma and axon hillock, but makes it less
likely for the neuron to fire an AP, unlike the EPSP that does the
opposite.
How strongly these EPSPs and IPSPs influence the likelihood of
an AP being fired depends on a range of factors, which are what
Ill be discussing next.
b) Summation (how individual inputs interact with one
another)
i)
Temporal summation
In most neurons, EPSPs and IPSPs cause only a small (less than
1mV) change in membrane potential. Hence, a large number of
EPSPs need to summate before threshold is reached and an AP
is fired. Furthermore, glutamate and GABA typically cause a
potential change that is quite brief (~10ms), with a fast rising
phase followed by a slower decay. The ability of EPSPs to
summate is therefore dependent on how quickly they are
activated in time. The summation of synaptic potentials over
time is called temporal summation.
The number of EPSPs required to bring the postsynaptic neuron
to threshold depends on a number of factors:
(1) The amplitude of each individual EPSP
If individual EPSPs are large in amplitude, then less EPSPs will
be required to depolarize the postsynaptic neuron to threshold
for AP generation.
(2) The time course of individual EPSPs and (3) how close
together in time EPSPs are generated.
If EPSPs have a slow time course, individual EPSPs will be able
to summate efficiently over time, even if each presynaptic
neuron produces EPSPs at very slow rates. The time course of a
synaptic potential and therefore the window for temporal
summation, is largely determined by properties of the

postsynaptic membrane. The neuronal membrane resistance and

capacitance, which are influenced by the membrane receptor
density and surface area respectively, will determine how
quickly the membrane potential changes when ion channels
open and current flows across the membrane. Typically, both
EPSPs and IPSPs have a small amplitude and a fast time course,
meaning that temporal summation will occur only when a large
number of presynaptic neurons release neurotransmitter at
approximately the same time.
However, EPSPs and IPSPs do not add up linearly, as the
generation of one EPSP/IPSP can affect the electrical driving
force for ion flow and hence the amplitude of subsequent EPSPs
/IPSPs. Usually, the second event is smaller owing to a reduced
driving force (nonlinear summation).
ii)

Spatial summation

This refers to the summation of EPSPs and IPSPs generated by

synapses at different locations. The extent of spatial summation
depends on how effectively they spread towards each other,
which in turn depends on the electrical properties of the
postsynaptic neuron's membrane and the geometry of the
dendritic tree. The neuronal membrane has leak channels, which
attenuate the synaptic potential as they spread along dendrites.
The neuronal membrane also acts as a capacitor, which slows
the postsynaptic potential changes (as the capacitance has to be
charged). The reduction in the amplitude of synaptic potentials
is, however, partly balanced by their increased duration.
Functionally, this means that as synaptic potentials spread to the
axon, they become smaller in amplitude, but longer in duration
and so better suited for integration over time (temporal
summation).
The spatial segregation of synaptic inputs on to different parts of
the dendritic tree has advantages. One advantage is the reduction
of nonlinear summation of synaptic potentials.

If all these excitatory were grouped tightly together on a small

area of the postsynaptic neuron, for example on one dendritic
branch, the generation of an EPSP at one synapse would
decrease the amplitude of EPSPs generated by the other
synapses as a consequence of a reduction in electrical driving
force. If the same synaptic connections were distributed over a
wide area, however, the local depolarisation produced by each
EPSP would have little effect on the electrical driving force for
EPSPs generated at the other synaptic connections.
c) Localisation of synapses
To trigger action potentials, synaptic potentials have to spread to
the axon hillock where the threshold is the lowest and action
potentials are initiated. Synaptic connections located closer to
the axon have the most influence on action potential generation.
Indeed, many neurons have inhibitory synapses placed precisely
at the axon hillock. These inhibitory inputs exerts a powerful
negative control, in essence vetoing the influence of all
excitatory synaptic input to the neuron. If the same group of
inhibitory inputs were moved to a localised region of the
dendritic tree, they would have a less powerful effect on action
potential generation, but would be better placed to inhibit EPSPs
generated locally in that part of the dendritic tree. An even more
specific way to control excitation occurs when the inhibitory
inputs are located presynaptically, that is directly on the nerve
terminals of excitatory presynaptic neurons. In this unique case
(called presynaptic inhibition) inhibitory input can modify the
output of a single synaptic connection.
The location of synapses within the neuron, therefore, has
important functional consequences. In general, synapses located
at sites remote from the axon hillock have a less powerful
control over neuronal output, unless mechanisms are in place to
compensate for the attenuation due to their remote location. For
example, the number of channels activated during a synaptic
potential could be larger at dendritic sites further away from the
axon. Alternatively, synaptic potentials generated at remote sites

may be amplified by voltage-activated channels similar to the

ion channels involved in the generation and propagation of
action potentials in the axon (discussed next).
d) voltage-gated ion channels in the dendritic tree
Voltage-gated ion channels are present in dendritic membranes alongside
ligand-gated ion channels that respond to neurotransmitter binding. The two
examples that I shall illustrate are sodium channels (much like those involved
in AP propagation) and NMDA receptors (which is both ligand and voltage
gated).

An action potential will be generated only if the balance of all excitatory and
inhibitory postsynaptic potentials at this site leads to a change in membrane
potential that crosses the threshold for action potential generation. The main
role of the dendritic tree is therefore to funnel synaptic inputs to the axon.