Biology Reference
In-Depth Information
C. Presynaptic involvement
LTP can be induced either by strong tetanic stimulation of a single pathway to a synapse,
or cooperatively via a weaker stimulation of many. This is due to the presence of a stimulus
threshold that must be reached in order to induce LTP. Associativity refers to the observation
that when weak stimulation of a single pathway is insufficient for the induction of LTP,
simultaneous strong stimulation of another pathway will induce LTP at both pathways.
Simultaneous activation of converging cortical and thalamic afferents specifically induced
associative, NMDA-receptor-dependent LTP at cortical, but not at thalamic, inputs (Humeau
et al. 2003). The induction of associative LTP at cortical inputs was found to be completely
independent of postsynaptic activity, including depolarization, postsynaptic NMDA receptor
activation or increases in postsynaptic Ca
2+
concentration, and did not require network
activity. LTP expression was mediated by a persistent increase in presynaptic release
probability at cortical afferents. Thus, the authors demonstrated the presynaptic induction and
expression of heterosynaptic and associative synaptic plasticity on simultaneous activity of
converging afferents. These data suggest that input specificity of associative LTP can be
determined exclusively by presynaptic properties, although it has been also demonstrated for
the amygdala that near coincidental pre- and postsynaptic action potentials induce associative
LTP or LTD, depending on the order of their timing. A presynaptic involvement in LA-LTP
induction was also described (Tsvetkov et al. 2002), when the EC-LA pathway was
stimulated in coronal slices. In this context, it is noteworthy to add that by immuno-electron
microscopy the
existence of presynaptic NMDARs in the LA has been evidenced (Farb et al.
1995).
Interestingly, inhibition of glutamate transporters leads to a loss of input specificity of
LTP in the amygdala slices, as assessed by monitoring synaptic responses at two independent
inputs converging on a single postsynaptic neuron. Diffusion of glutamate ("spillover") from
stimulated synapses, paired with postsynaptic depolarization, is sufficient to induce LTP in
the heterosynaptic pathway, whereas an enzymatic glutamate scavenger abolishes this effect.
These results establish active glutamate uptake as a crucial mechanism maintaining the
pathway specificity of LTP in the neural circuitry of fear conditioning (Tsvetkov et al. 2004).
Furthermore, using a combined genetic and electrophysiological approach, it recently has
been shown that the lack of a specific GABA
B
receptor subtype, GABA
B
(1a,2), unmasks a
nonassociative, NMDA receptor-independent form of presynaptic LTP at cortico-amygdala
afferents (Shaban et al. 2006). Moreover, these authors show that the level of presynaptic
GABA
B
(1a,2) receptor activation, and hence the balance between associative and
nonassociative forms of LTP, could be dynamically modulated by local inhibitory activity. At
the behavioral level, genetic loss of GABA
B
(1a) resulted in a generalization of conditioned
fear to nonconditioned stimuli.
In addition to the recently demonstrated presynaptic location of NMDA receptors, it is
well known that the group II mGluRs, mGluR 2 and 3, are found in a high concentration
presynaptically and also at a lower concentration postsynaptically. In the BLA presynaptic
(Neugebauer et al. 1997) as well postsynaptic effects (Rainnie et al. 1994) of group II mGluR
agonists have been shown. It has been demonstrated that LTD can be also induced by
activation of group II mGLURs in the BLA. This chemically-induced LTD was NMDA-
independent and required synaptic activation and presynaptic, but not postsynaptic, Ca
2+
increase and was associated with an increase in paired pulse facilitation (Lin et al. 2000). In
