Biomedical Engineering Reference
In-Depth Information
Recent experimental evidence indicates that spontaneous transmission serves
important roles in neuronal communication. Spontaneous GABA release provides
continuous background inhibition and sets the inhibitory tone of postsynaptic
neurons (Otis et al.
1991
; Lu and Trussell
2000
), and spontaneous release has
been hypothesized to regulate receptor clustering and neuronal excitability parti-
cularly at high levels of input resistance (Saitoe et al.
2001
; Carter and Regehr
2002
; Sharma and Vijayaraghavan
2003
). Convincing evidence exists that sponta-
neous release affects the local dendritic signal transduction systems and protein
translation machinery (Sutton et al.
2007
), thereby modulating postsynaptic
responsivity (Sutton et al.
2004
,
2006
,
2007
). Spontaneous release represents the
only cross talk between the presynaptic and the postsynaptic neuron in silent
synapses, with a central trophic role for the postsynaptic neuron, triggering signal-
ing, maturation, and stability of neural networks. Moreover, it is the main target of
homeostatic plasticity mechanisms: when neurons are chronically deprived of
activity or subjected to prolonged hyperactivity, spontaneous release responds
with compensatory changes in the frequency and amplitude of the events, trying
to rescue the initial set point of synaptic activity.
Several studies have debated whether the spontaneous release activity depends
on a specific pool of SVs endowed with distinct molecular markers present in all
synapses (e.g., Vti1a or VAMP7 positive) or reflects a specialization of certain
populations of synapses that exhibit a very low probability for evoked release
(Ramirez and Kavalali
2011
). Interestingly, spontaneous neurotransmission seems
to use specific postsynaptic pathways for information transfer. Indeed, a subset of
ionotropic NMDA-type glutamate receptors appears to be selectively activated by
this particular modality of release. Treatment with MK-801, a high-affinity
use-dependent open channel blocker of NMDA receptors, strongly reduces mini-
ature NMDA-mediated currents, leaving NMDA receptor activation in response to
subsequent evoked release unaffected. Multichannel parallel signaling is a common
feature of ICT networks. These parallel communication channels cooperate with
the main, time-locked information transfer channel (i.e., the synchronous release)
and ensure error correction, maintenance, and connectivity. Thus, it is likely that
spontaneous transmission, far from simply being the expression of the stochastic
overcoming of the fusion energy barrier for exocytosis (basal
fusion willingness
of
SVs) or
synaptic noise
, plays a key function in maintaining a tight synaptic
homeostasis and connectivity within a large dynamic range for reliable information
transfer and storage.
9.3.2 Synchronous and Asynchronous Release
Fast neurotransmitter release is tightly time-locked (less than 0.5-1 ms delay) to the
action potential (Sabatini and Regehr
1996
). Such a process is fundamental for the
timing and high fidelity of neuronal communication. However, neurotransmitter
quanta are also released with some delay in response to Ca
2+
entry in a sustained,
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