The Basolateral Amygdala Sends a Mixed (GABAergic and Glutamatergic) Projection to the Mediodorsal Thalamic Nucleus

The medial prefrontal cortex receives converging inputs from the mediodorsal thalamic nucleus (MD) and basolateral amygdala (BLA). Although many studies reported that the BLA also projects to MD, there is conflicting evidence regarding this projection, with some data suggesting that it originates from GABAergic or glutamatergic neurons. Therefore, the present study aimed to determine the neurotransmitter used by MD-projecting BLA cells in male and female rats. We first examined whether BLA cells retrogradely labeled by Fast Blue infusions in MD are immunopositive for multiple established markers of BLA interneurons. A minority of MD-projecting BLA cells expressed somatostatin (∼22%) or calretinin (∼11%) but not other interneuronal markers, suggesting that BLA neurons projecting to MD not only include glutamatergic cells, but also long-range GABAergic neurons. Second, we examined the responses of MD cells to optogenetic activation of BLA axons using whole-cell recordings in vitro Consistent with our immunohistochemical findings, among responsive MD cells, light stimuli typically elicited isolated EPSPs (73%) or IPSPs (27%) as well as coincident EPSPs and IPSPs (11%). Indicating that these IPSPs were monosynaptic, light-evoked EPSPs and IPSPs had the same latency and the IPSPs persisted in the presence of ionotropic glutamate receptor antagonists. Overall, our results indicate that the BLA sends a mixed, glutamatergic-GABAergic projection to MD, which likely influences coordination of activity between BLA, MD, and medial prefrontal cortex. An important challenge for future studies will be to examine the connections formed by MD-projecting glutamatergic and GABAergic BLA cells with each other and other populations of BLA cells.SIGNIFICANCE STATEMENT The mediodorsal thalamic nucleus (MD) and basolateral amygdala (BLA) send convergent projections to the medial prefrontal cortex. Although many studies reported that the BLA also projects to MD, there is conflicting evidence as to whether this projection is glutamatergic or GABAergic. By combining tract tracing, immunohistochemistry, optogenetics, and patch clamp recordings in vitro, we found that BLA neurons projecting to MD not only include glutamatergic cells, but also long-range GABAergic neurons. Differential recruitment of these two contingents of cells likely influences coordination of activity between the BLA, MD, and medial prefrontal cortex.