Glutamate plasticity in the drunken amygdala: the making of an anxious synapse

Abstract

Plasticity at glutamatergic synapses is believed to be the cellular correlate of learning and memory. Classic fear conditioning, for example, is dependent upon NMDA-type glutamate receptor activation in the lateral/basolateral amygdala followed by increased synaptic expression of AMPA-type glutamate receptors. This review provides an extensive comparison between the initiation and expression of glutamatergic plasticity during learning/memory and glutamatergic alterations associated with chronic ethanol exposure and withdrawal. The parallels between these neuro-adaptive processes suggest that long-term ethanol exposure might "chemically condition" amygdala-dependent fear/anxiety via the increased function of pre- and post-synaptic glutamate signaling.

Figure 1

Model describing glutamatergic alterations measured in lateral/basolateral amygdala principal neurons following chronic ethanol exposure and withdrawal. Pre-synaptic (purple) and post-synaptic (green) specializations represent a ‘generic’ glutamatergic synapse. Synaptic responses mediated by postsynaptic AMPA (red)- , kainate (blue)-, and NMDA (yellow)-type glutamate receptors can be measured in ethanol naïve (left) neurons (Lack et al., 2008; Lack et al., 2009; Lack et al., 2007). Chronic ethanol exposure (middle) enhances NMDA and kainate receptor synaptic function (here represented as increased numbers of receptors found at the postsynaptic specialization) and increases the probability of glutamate release measured by paired stimuli and the frequency spontaneous AMPA mediated synaptic events. Since this effect is sensitive to tetrodotoxin, we presume presynaptic alterations involve voltage- or calcium-dependent processes. During withdrawal (right), kainate receptor-mediated synaptic responses return to control levels while AMPA receptor-mediated responses are markedly increased, possibly due to increased numbers of receptors at the synapse. Like chronic ethanol, withdrawal also increases presynaptic function but these changes become resistant to tetrodotoxin–here represented as increased numbers of vesicles but could also involve increases in the probability of release or quantal content at single synapses or increases in the total number of release sites. See text for details.