• Position (eccentricity) of the released vesicle
• Ca
2+ different modulations of the SNARE complex
2.1.2 Postsynaptic-dependent EPSP variability
The PSD is the postsynaptic area containing the receptors (AMPA and NMDA)
with different roles [44]. The number of receptors among different synapses is
highly variable but varies also in the same synapse as a function of its maturity and
activity. The number of AMPA receptors in a typical hippocampal synapse can
range between 0 (AMPA-silent synapses [45]) and 80–100 [46, 47]. The number
of AMPA is related to the synaptic maturation and potentiation and is strongly
associated to phenomena like memory formation and learning (among many
others [17, 29, 48–51]). Some of these mechanisms can change the properties of a
synapse in the time-lapse of less than a second if the presynaptic neuron furnishes
an appropriate stimulation. The variability of the number of AMPA not only
produces potentiation of a synapse but also a depotentiation (by removing of
AMPA [52]), and both mechanisms are Ca
2+ and NMDA dependent [53]. AMPA
can either be inserted (or removed) because a migration from the extrasynaptic
membrane space to the PSD or just aquired from the cytoplasm [52]. According
to some authors, also the number of NMDA receptors can change as a function of
the activity [54]. This point is not trivial for the understanding of the synaptic
response variability. By changing the number of receptors, it changes the total
conductance and the current that the synapse can produce for a single presynaptic
spike (see Figure 2).
Both AMPA and NMDA are tetramers (composed of four subunits) arranged as
dimer of dimers. The dimeric and tetrameric composition produces a mosaic of
configurations each with electrophysiological properties different from the others
[24, 55–60]. Their conductances mediated over different dimeric compositions (as
computed in Di Maio et al. Table 2 of [61]), in fact, are for AMPA 15 Æ 10 pS and for
NMDA 40 Æ 15 pS. This means that the variability induced by the insertion activitydependent of an AMPA, for example, will furnish a variation of the response
depending on the dimeric composition (conductance) of the newly inserted
receptor.
The current produced by the opening of the receptors (EPSC) produces a
variation of the membrane potential (EPSP) at the postsynaptic side which depends
on the biophysical properties of the postsynaptic membrane. The glutamatergic
Figure 2.
Different synaptic responses obtained for the release of a single vesicle. The different amplitudes can be due either
for presynaptic regulation (e.g., different positions of the vesicle or different numbers of molecules) or for
postsynaptic regulation (e.g., different numbers of receptors or different membrane voltage at the moment of the
EPSP start).
97
Information Processing and Synaptic Transmission
DOI: http://dx.doi.org/10.5772/intechopen.88405
• Ca
2+ different modulations of the SNARE complex
2.1.2 Postsynaptic-dependent EPSP variability
The PSD is the postsynaptic area containing the receptors (AMPA and NMDA)
with different roles [44]. The number of receptors among different synapses is
highly variable but varies also in the same synapse as a function of its maturity and
activity. The number of AMPA receptors in a typical hippocampal synapse can
range between 0 (AMPA-silent synapses [45]) and 80–100 [46, 47]. The number
of AMPA is related to the synaptic maturation and potentiation and is strongly
associated to phenomena like memory formation and learning (among many
others [17, 29, 48–51]). Some of these mechanisms can change the properties of a
synapse in the time-lapse of less than a second if the presynaptic neuron furnishes
an appropriate stimulation. The variability of the number of AMPA not only
produces potentiation of a synapse but also a depotentiation (by removing of
AMPA [52]), and both mechanisms are Ca
2+ and NMDA dependent [53]. AMPA
can either be inserted (or removed) because a migration from the extrasynaptic
membrane space to the PSD or just aquired from the cytoplasm [52]. According
to some authors, also the number of NMDA receptors can change as a function of
the activity [54]. This point is not trivial for the understanding of the synaptic
response variability. By changing the number of receptors, it changes the total
conductance and the current that the synapse can produce for a single presynaptic
spike (see Figure 2).
Both AMPA and NMDA are tetramers (composed of four subunits) arranged as
dimer of dimers. The dimeric and tetrameric composition produces a mosaic of
configurations each with electrophysiological properties different from the others
[24, 55–60]. Their conductances mediated over different dimeric compositions (as
computed in Di Maio et al. Table 2 of [61]), in fact, are for AMPA 15 Æ 10 pS and for
NMDA 40 Æ 15 pS. This means that the variability induced by the insertion activitydependent of an AMPA, for example, will furnish a variation of the response
depending on the dimeric composition (conductance) of the newly inserted
receptor.
The current produced by the opening of the receptors (EPSC) produces a
variation of the membrane potential (EPSP) at the postsynaptic side which depends
on the biophysical properties of the postsynaptic membrane. The glutamatergic
Figure 2.
Different synaptic responses obtained for the release of a single vesicle. The different amplitudes can be due either
for presynaptic regulation (e.g., different positions of the vesicle or different numbers of molecules) or for
postsynaptic regulation (e.g., different numbers of receptors or different membrane voltage at the moment of the
EPSP start).
97
Information Processing and Synaptic Transmission
DOI: http://dx.doi.org/10.5772/intechopen.88405