Distinct aversive states in the mouse medial prefrontal cortex.

It was recently shown that glutamatergic neurons in the lateral hypothalamus (LHA) projecting to the lateral habenula (LH) encode negative value. However, it is still unclear how such aversive neuronal pathways located in subcortical neuronal populations affect the activity of the rest of the brain. We report here how the neuronal activity in an integrative cortical area previously reported to be involved in aversion, the medial prefrontal cortex (mPFC), is modulated when an internal aversive signal is emitted in the hypothalamic-habenula (LHA-LH) pathway. We have used a transgenic mouse line (VGlut2-cre) to determine the role of the LHA-LH pathway in signaling the aversive state in (mPFC). We recorded from 2569 single units using dense extracellular recordings (Neuropixels) in combination with optogenetic activation to determine the neural signature across prefrontal subregions (anterior cingulate area, dorsal part (ACAd), prelimbic area (PL), infralimbic area (ILA), and orbitofrontal area, medial part (ORBm)). We found that the specific activation of the aversive LHA-LH pathway elicited distinct activity signatures in the mPFC, suggesting a central role of the PL in response to internal aversive signals. Interestingly, the induced activity dynamics showed region-specific patterns that were decodable from the spontaneous spiking activity, supporting that the PL and the ORBm carry distinct signatures of the aversive state.