Optogenetic study of central medial and paraventricular thalamic projections to the basolateral amygdala.

The central medial (CMT) and paraventricular (PVT) thalamic nuclei project strongly to the basolateral amygdala (BL). Similarities between the responsiveness of CMT, PVT, and BL neurons suggest that these nuclei strongly influence BL activity. Supporting this possibility, an electron microscopic study reported that, in contrast with other extrinsic afferents, CMT and PVT axon terminals form very few synapses with BL interneurons. However, since limited sampling is a concern in electron microscopic studies, the present investigation was undertaken to compare the impact of CMT and PVT thalamic inputs on principal and local-circuit BL neurons with optogenetic methods and whole cell recordings in vitro. Optogenetic stimulation of CMT and PVT axons elicited glutamatergic excitatory postsynaptic potentials (EPSPs) or excitatory postsynaptic currents (EPSCs) in principal cells and interneurons, but they generally had a longer latency in interneurons. Moreover, after blockade of polysynaptic interactions with tetrodotoxin (TTX), a lower proportion of interneurons (50%) than principal cells (90%) remained responsive to CMT and PVT inputs. Although the presence of TTX-resistant responses in some interneurons indicates that CMT and PVT inputs directly contact some local-circuit cells, their lower incidence and amplitude after TTX suggest that CMT and PVT inputs form fewer synapses with them than with principal BL cells. Together, these results indicate that CMT and PVT inputs mainly contact principal BL neurons such that when CMT or PVT neurons fire, limited feedforward inhibition counters their excitatory influence over principal BL cells. However, CMT and PVT axons can also recruit interneurons indirectly, via the activation of principal cells, thereby generating feedback inhibition. Midline thalamic (MTh) nuclei contribute major projections to the basolateral amygdala (BL). Similarities between the responsiveness of MTh and BL neurons suggest that MTh neurons exert a significant influence over BL activity. Using optogenetic techniques, we show that MTh inputs mainly contact principal BL neurons such that when MTh neurons fire, little feedforward inhibition counters their excitatory influence over principal cells. Thus, MTh inputs may be major determinants of BL activity.