Dopaminergic modulation of spontaneous inhibitory network activity in the lateral amygdala

There is converging evidence that dopamine (DA) receptor activation in the lateral amygdala (LA) is required for the acquisition of conditioned fear. Powerful inhibitory circuits exist in the LA shaping the activity of excitatory projection neurons and controlling the induction of associative plasticity, which is thought to underlie fear learning. In vivo and in vitro electrophysiological experiments indicate that DA suppresses inhibitory transmission triggered by excitatory afferent input. Conversely, DA increases the excitability of inhibitory interneurons in the LA. However, the mechanisms by which DA modulates inhibitory transmission are poorly understood. Using whole-cell recordings from LA projection neurons in coronal mouse brain slices, we found that DA strongly increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs). In addition, DA application induced low-frequency (2-6 Hz) oscillatory activity of inhibitory circuits in the absence of excitatory input. The increase in sIPSC frequency required activation of D1-like receptors. Unlike D1 receptor-mediated transmission in other brain areas, this effect was independent of the cAMP/PKA signal transduction cascade, but involved activation of the protein tyrosine kinase Src. This indicates that DA orchestrates the activity of populations of interneurons in the LA by a D1-dependent, non-canonical signal transduction pathway.