Grant: CIHR Fellowship

Rapid eye movement (REM) sleep is important for processing emotional memories. REM sleep is defined by a distinct pattern of functional brain connectivity: a signaling loop including the hippocampus (HP), amygdala (AM) and prefrontal cortex (PF). In mice, REM sleep functional connectivity is associated with theta synchronization of the HP/AM/PF field potentials. The involvement of brainstem REM sleep control centers in driving this connectivity is undetermined. The proposed research will: (i) identify what REM-active brainstem pathway(s) drive HP/AM/PF theta synchronization in REM sleep, and (ii) determine the necessity of REM sleep theta synchrony, and the enabling brainstem pathways, in emotional memory consolidation. I hypothesize that signaling between GABAergic CeA neurons and the SLD is required for HP/AM/PF theta synchrony during REM sleep. Preliminary data shows that selective inhibition of hM4Di-expressing GABAergic CeA neurons prevents HP/AM/PF theta rhythm synchrony in REM sleep. To test the specific involvement of the SLD pathway, an anterograde trans-synaptic tagging approach is used. The use of optrode recording is proposed: (i) to identify the firing characteristics of CeA targeted SLD neurons and (ii) to identify the effect of activating CeA targeted SLD neurons on the firing local REM sleep-active theta synchronized cells. I hypothesize that activation of these neurons will: (i) disrupt firing in the theta-active population locally and, (ii) disrupt global HP/AM/PF theta rhythm synchrony. To identify the functional importance of this amygdalo-pontine pathway in REM sleep related emotional memory consolidation, GABAergic CeA neurons and CeA targeted SLD neurons will be optogenetically inhibited following a standard fear conditioning protocol. I hypothesize that neuronal silencing will disrupt HP/AM/PF theta synchronization and attenuate subsequent contextual and cued recall: evidence of impaired emotional memory consolidation.