Midbrain circuits for defensive behavior

MARIA SOLEDAD ESPOSITO; PHILIP TOVOTE; PAOLO BOTTA; FABRICE CHAUDUN; JONATHAN P. FADOK; STEFFEN B. E. WOLFF; MILICA MARKOVIC; CHARU RAMAKRISHNAN; KARL DEISSEROTH; CYRIL HERRY; SILVIA ARBER; ANDREAS LÜTHI

Mar del Plata

Congreso; XXX SAN; 2015

The periaqueductal grey (PAG) is a central part of the circuitry that elicits defensive behaviors in aversive situations. Previous research has shown that the PAG is organized into functionally distinct columns, with the dorsolateral and lateral (dl/lPAG) columns producing flight and the ventrolateral column (vlPAG) being responsible for freezing. However, little is known about functional roles of neuronal subpopulations within these regions in the expression of active and passive defensive behaviors. We used optogenetics, neuronal recordings, and tracing techniques to characterize circuits important for innate and fear-evoked freezing and flight. Active defensive behaviors were evoked by optical activation of dl/lPAG glutamatergic cells, while freezing was observed after activation of vlPAG glutamatergic cells or inhibition of GABAergic cells in the PAG. Freezing behavior correlated with both enhanced as well as reduced single-unit activity in the PAG. Slice recordings and rabies tracing revealed preferential connectivity of GABAergic CEA inputs onto GABAergic vlPAG cells, and local GABAergic input onto glutamatergic vlPAG cells. Our data suggests that inhibitory input from the amygdala onto GABAergic cells of the PAG produces freezing by disinhibition of glutamatergic vlPAG outputs. Specific optogenetic activation of glutamatergic vlPAG output to the magnocellular nucleus of the medulla resulted in freezing behavior. In summary, we here present novel insights into the circuit mechanisms underlying defensive behaviors.