The Temporal Expression Patterns of CREB Governing Long-Term Memory Formation

The cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) is a nodal transcription factor that has been hypothesized to be a molecular switch governing the formation of long-term memories in the mammalian brain. The present thesis takes advantage of a novel optogenetic regulator of CREB, applying it for the first time in an in vivo system, to present the first evidence showing that a temporally-restricted elevation in CREB function, in a small proportion of neurons in the lateral amygdala (LA), is sufficient to enhance the formation of long-term memories in a living mouse. Specifically, a restricted spike in CREB function in a small proportion of LA neurons one hour before learning is sufficient to enhance the encoding of an auditory fear memory. These results, in combination with the existing literature, suggest that the timing of variations in endogenous CREB function govern the formation or forgetting of long-term memories.M.Sc