Prefrontal Cortex Drives Distinct Projection Neurons in the Basolateral Amygdala

The prefrontal cortex (PFC) regulates emotional behavior via top-down control of the basolateral amygdala (BLA). However, the influence of PFC inputs on the different projection pathways within the BLA remains largely unexplored. Here, we combine whole-cell recordings and optogenetics to study these cell-type specific connections in mouse BLA. We characterize PFC inputs onto three distinct populations of BLA neurons that project to the PFC, ventral hippocampus, or nucleus accumbens. We find that PFC-evoked synaptic responses are strongest at amygdala-cortical and amygdala-hippocampal neurons and much weaker at amygdala-striatal neurons. We assess the mechanisms for this targeting and conclude that it reflects fewer connections onto amygdala-striatal neurons. Given the similar intrinsic properties of these cells, this connectivity allows the PFC to preferentially activate amygdala-cortical and amygdala-hippocampal neurons. Together, our findings reveal how PFC inputs to the BLA selectively drive feedback projections to the PFC and feedforward projections to the hippocampus. McGarry and Carter report that the prefrontal cortex (PFC) contacts three distinct populations of projection neurons in the BLA, with the strongest inputs onto neurons that project back to the PFC and to the hippocampus and the weakest inputs onto neurons that project to the striatum.