Abstract Traumatic brain injury is the most common neurological disorder and 80% consist of mild traumatic brain injury (mTBI). The severity and persistence of cognitive symptoms is increased with additional repeat mTBIs (rmTBI). A high frequency head impact (HF-HI) mouse model of rmTBI developed by the Burns lab displays decreased learning and changes in transcriptomic profiles related to synaptic signaling accompanied by decreased plasticity and synaptic changes in CA1 pyramidal neurons. This would suggest that synaptic modifications underly the anterograde cognitive symptoms following rmTBI. It is still unknown how rmTBI directly effects an already established memory. Engrams, defined as lasting physical or chemical changes in neurons, are the neural substrate underlying episodic memory. Studies in transgenic rodents use immediate early genes and pharmacological labeling, can tag engram cells in contextual fear conditioning (CFC) paradigms. Subsequent optogenetic reactivation of engrams in the hippocampal formation is sufficient to elicit memory recall outside the conditioned context and reanimate fear memories in models of amnesia. Preliminary data has shown that the HF-HI model reduces freezing time in CFC probe trials and engram cells expressing Chr2-YFP can be tagged in transgenic engram mice. I propose to interrogate immunohistological and electrophysiological properties of engram cells to explore architectural or synaptic modifications in the repeat head impact brain. I will also use optogenetics in vivo to reanimate amnestic memories. This research will explore how synaptic modification relates to retrograde cognitive deficits following rmTBI and probe memory recall, not memory substrate loss, as a mechanism for retrograde amnesia.