The GABAergic neurons of the rostral Zona Incerta (ZIr) directly innervate the excitatory neurons of the dorsal periaqueductal gray matter (dPAG) and modulate the defense behavior. The scope of this work is to determine through optogenetic techniques and using transgenic mice expressing CRE-recombinase in GABAergic neurons, how the GABAergic influences in the dorsal PAG modulates the gain of innate defensive responses and the extinction of contextual defensive responses in a predatory situation. We will first determine all sources of GABAergic projections to dorsal PAG using retrograde adeno-associated virus (AAV) expressing the m-Cherry fluorescent protein. Next, using CRE-dependent retrograde adeno-associated virus (AAV) expressing Channelrhodopsin type 2 (ChR2), we will examine how the optogenetic activation of Zr-GABAergic neurons modulates innate and contextual defensive responses of predator-exposed animals. Finally, injecting the ZIr with CRE-dependent AAV-expressing ChR2, we will examine how the optogenetic activation of the Zr-GABAergic fibers that innervate the dorsal PAG modulate these innate and contextual anti-predatory responses.
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