Synaptic mechanisms underlying strong reciprocal connectivity between the medial prefrontal cortex and basolateral...

The medial prefrontal cortex (mPFC) plays a critical role in the control of cognition and emotion. Reciprocal circuits between the mPFC and basolateral amygdala (BLA) are particularly important for emotional control. However, the neurons and synapses that link these brain regions remain largely unknown. Here we examine long-range connections between the mouse mPFC and BLA, using whole-cell recordings, optogenetics, and two-photon microscopy. We first identify two non-overlapping populations of layer 2 pyramidal neurons that directly project to either the BLA or contralateral mPFC. We then show that pyramidal neurons projecting to the BLA receive much stronger excitatory inputs from this same brain region. We next assess the contributions of both presynaptic and postsynaptic mechanisms to this cell-type and input-specific connectivity. We use two-photon mapping to reveal differences in both the synaptic density and subcellular targeting of BLA inputs. Finally, we simulate and experimentally validate how the number, volume, and location of active spines all contribute to preferential synaptic drive. Together, our findings reveal a novel and strong reciprocal circuit that is likely to be important for how the mPFC controls cognition and emotion.