Complexity and Computation at the Synapse: Multilayer Architecture and Role of Diffusion in Shaping Synaptic Activity and Computation - Bioinspired Approaches for Human-Centric Technologies - page 279

decay kinetics has been explained by the fact that GluK2/K5 receptors possess two
different types of binding sites showing distinct affinity and desensitization prop-
erties. In particular, glutamate binding to the high-affinity sites induces poor
desensitization, while activation of low-affinity binding sites determines fast and
profound GluK2/K5 desensitization (Mott et al. 2010 ). During fast synaptic acti-
vation, therefore, the high-affinity/poorly desensitizing binding site is preferentially
activated, mediating hence slow decaying responses.
Another interesting dependence of GABAergic current kinetics upon the time
course of presynaptic GABA is provided by the slow inhibitory postsynaptic
currents (slow IPSCs) first observed in the CA1 regions of the hippocampus (Pearce
1993 ; Banks et al. 1998 ). These particular forms of GABAergic synaptic current,
characterized by slow onset and decay kinetics, have been shown to be mediated by
the neurogliaform cells (NGFCs), specific interneuron subtype located in the
stratum lacunosum moleculare . Ultrastructural and electrophysiological investi-
gations clarified that the presynaptic boutons of NGFCs are distant from the
postsynaptic element, thus determining GABA “volume release” (Szabadics
et al. 2007 ; Ol´h et al. 2009 ). Karayannis et al. ( 2010 ), using a quantitative
approach, demonstrated that slow IPSCs are, by a slow and low-concentration
GABA transient (1-60 M, 20-200 ms), compatible with the “volume release”

from NGFC boutons to pyramidal cells.

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9.4.3 Neurotransmitter Diffusion Outside the Synaptic Cleft

In conventional synaptic transmission, the information transfer mediated by neu-
rotransmitter release is believed to be restricted to the pre- and postsynaptic
elements of the same synapse. It has been argued that these conditions of “synapse
independence” would maximize the information storage capacity of the brain
(Barbour 2001 ). However, several lines of evidence indicate that, after synaptic
release, neurotransmitter can diffuse out the synaptic cleft thus activating both
postsynaptic receptors belonging to neighbor synapses and receptors expressed at
the presynaptic level (Trussell et al. 1993 ; Rusakov and Kullmann 1998 ; Isaacson
1999 ; Digregorio et al. 2002 ; Arnth-Jensen et al. 2002 ; Chalifoux and Carter 2011 ;
Scanziani et al. 1997 ; Mitchell and Silver 2000a , b ). This phenomenon, referred to
as “neurotransmitter spillover,” has been shown to play a central role in the
modulation of the synaptic activity.
At the presynaptic level, the activation of high-affinity neurotransmitter recep-
tors (mGluR, GABAB) reduces the glutamate release (Mitchell and Silver 2000a , b )
and increases the threshold for LTP (Vogt and Nicoll 1999 ). At the postsynaptic
level, neurotransmitter spillover has been extensively demonstrated to activate the
high-affinity NMDA glutamate receptors at Asztely et al. ( 1997 ), Arnth-Jensen
et al. ( 2002 ), and Chalifoux and Carter ( 2011 ). Rusakov and Kullmann ( 1998 )by
using model simulations estimated that a single quantum of glutamate can escape
the synaptic cleft and reach (although to a considerably lower concentration)