Abstract
Synaptic plasticity in the amygdala is essential for emotional learning. Fear conditioning, for example, depends on changes in excitatory transmission that occur following NMDA receptor activation and AMPA receptor modification in this region. The role of these and other glutamatergic mechanisms have been studied extensively in this circuit while relatively little is known about the contribution of inhibitory transmission. The current experiments addressed this issue by examining the role of the GABA(A) receptor subunit α1 in fear learning and plasticity. We first confirmed previous findings that the α1 subunit is highly expressed in the lateral nucleus of the amygdala. Consistent with this observation, genetic deletion of this subunit selectively enhanced plasticity in the lateral amygdala and increased auditory fear conditioning. Mice with selective deletion of α1 in excitatory cells did not exhibit enhanced learning. Finally, infusion of a α1 receptor antagonist into the lateral amygdala selectively impaired auditory fear learning. Together, these results suggest that inhibitory transmission mediated by α1-containing GABA(A) receptors plays a critical role in amygdala plasticity and fear learning.
Highlights
Fear conditioning is a highly conserved form of emotional learning that occurs when stimuli in the environment predict aversive events
Immunolabeling of α1 was highest in the lateral nucleus (LA), relatively low in the basolateral nucleus (BLA), and virtually absent in the central nucleus, where the level of labeling was similar to the background labeling in the optic tract (Figures 1A,C)
Given that αCaMKII is selectively expressed in excitatory cells in the lateral and basolateral amygdala (McDonald et al, 2002) these results suggest that the loss of α1 in inhibitory neurons is likely responsible for the increased auditory fear conditioning observed in global knockout mice
Summary
Fear conditioning is a highly conserved form of emotional learning that occurs when stimuli in the environment predict aversive events. The central nucleus serves as an output structure capable of activating a variety of fear responses via its connections with the hypothalamus and periaqueductal grey (Fendt and Fanselow, 1999; LeDoux, 2000; Nader et al, 2001) This compartmentalization is observed in the genetic anatomy of the amygdala. The α1 subunit of the GABA receptor is highly expressed in the lateral amygdala, moderately expressed in the BLA and completely absent from the central nucleus (Fritschy and Mohler, 1995; Kaufmann et al, 2003; Marowsky et al, 2004; McDonald and Mascagni, 2004) The function of this differential genetic expression pattern is currently unknown
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