TY - JOUR T1 - Specific targeting of the basolateral amygdala to projectionally defined pyramidal neurons in prelimbic and infralimbic cortex JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0002-16.2016 SP - ENEURO.0002-16.2016 AU - John Cheriyan AU - Mahesh K. Kaushik AU - Ashley N. Ferreira AU - Patrick L. Sheets Y1 - 2016/03/12 UR - http://www.eneuro.org/content/early/2016/03/11/ENEURO.0002-16.2016.abstract N2 - Adjacent prelimbic (PL) and infralimbic (IL) regions in the medial prefrontal cortex (mPFC) have distinct roles in emotional learning. A complete mechanistic understanding underlying this dichotomy remains unclear. Here we explored targeting of specific PL and IL neurons by the basolateral amygdala (BLA), a limbic structure pivotal in pain and fear processing. In mice, we used retrograde labeling, brain slice recordings, and adenoviral optogenetics to dissect connectivity of ascending BLA input onto PL and IL neurons projecting to the periaqueductal gray (PAG) or the amygdala. We found differential targeting of BLA projections to PL and IL cortex. Activating BLA projections evoked excitatory and inhibitory responses in cortico-PAG (CP) neurons in layer 5 (L5) of both PL and IL cortex. However, all inhibitory responses were polysynaptic and monosynaptic BLA input was stronger to CP neurons in IL cortex. Conversely, the BLA preferentially targeted corticoamygdalar (CA) neurons in L2 of PL over IL cortex. We also reveal that BLA input is projection specific by showing preferential targeting of L5 CP neurons over neighboring L3/5 CA neurons in IL cortex. We conclude by showing that BLA input is laminar specific by producing stronger excitatory responses CA neurons in L3/5 compared to L2 in IL cortex. Collectively, this study reveals differential targeting of the BLA to PL and IL cortex which depends both on laminar location and projection target of cortical neurons. Overall, our findings should have important implications for understanding the processing of pain and fear input by the PL and IL cortex.Significance Statement: The prelimbic (PL) and infralimbic (IL) cortices are comprised of a heterogeneous population of pyramidal neurons that receive, integrate, and relay information ascending from subcortical (long-range) origins. For the first time, we address critical unknowns regarding long-range targeting of the basolateral amygdala (BLA) to specific PL and IL neurons projecting to key subcortical structures involved in pain and fear, the periaqueductal gray (PAG) and the amygdala. Our data reveal a distinctive pattern of BLA input to these neurons demonstrating that BLA-mPFC connections are region, laminar and projection specific. Elucidating the organization and strength of long-range connections to specific neurons in the PL and IL cortex provides valuable insight into cortical processing of outputs relevant in pain and anxiety disorders. ER -