Neuronal circuits for expression of active versus passive defensive behaviors

PHILIP TOVOTE; MARIA SOLEDAD ESPOSITO; STEFFEN B. E. WOLFF; JONATHAN P. FADOK; Z. J. HUANG; SILVIA ARBER; ANDREAS LÜTHI

New Orleans

Congreso; Society for Neuroscience; 2012

Society for Neuroscience

The midbrain periaqueductal gray (PAG) mediates adaptive defensive responses to aversive stimuli. It plays a major role in expression of passive (e.g. freezing) and active (e.g. flight) fear responses. Via a strong projection to the PAG, the central nucleus of the amygdala (CeA) mediates behavioral fear responses. Little is known about circuit mechanisms within the PAG underlying those behaviors and rapid switching between them. We first identified the projections from CeA to PAG using retrograde tracing in GAD67-GFP mice. We then took an optogenetic approach in mice to identify cell types within lateral (lPAG) and ventrolateral (vlPAG) columns of PAG contributing to freezing versus flight responses. Channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR) were first unconditionally expressed in lPAG and vlPAG. Light activation of ChR2 in vlPAG neurons resulted in strong freezing behavior, whereas flight responses could be evoked in mice with widespread ChR2 expression within lPAG. We next conditionally expressed ChR2 and NpHR within specific subpopulations of neurons in lPAG and vlPAG. Upon light stimulation, various defensive behaviors ranging from freezing to flight were observed. In vivo single-unit recordings revealed strong correlation between freezing and neuronal activity. For retrograde tracing of pre-motor circuits for freezing and flight downstream of PAG, we injected mutated rabies virus into spinal cord and forelimb muscles of mice. Rabies-infected cells were found in medullary axonal projection areas of PAG neurons such as lateral paragigantocellular and pontine reticular nuclei. Our findings confirm involvement of lPAG neurons in flight behavior, whereas vlPAG cells contribute to freezing, and suggest specific roles of defined neuronal subpopulations within PAG for expression of passive versus active defensive behavior.