WHEN AND HOW DOES OUR BRAIN INTEGRATE MEMORIES?

Memories are constantly formed and retrieved in our brain. Our brain having encoded a set of information, can store subsequent related information using the initial memory as a substrate. Here we propose and test if such related events are integrated rather than being encoded as discrete events while maintaining their distinctive identity and preserving their interrelationship. We employed virus based gene delivery systems for targeted ensemble activity manipulation, biochemical and behavioural assays, in- vivo imaging, ML based classifiers for following the dynamics of memory integration. Our results show that after training the subjects in two related contexts, extinguishing the memory for one context affects the other contextual memory asymmetrically. The memory that was acquired second showed a strong coupling/dependence on the memory of a prior event. Our study further indicates that while this cross dependence was abolished by small GTPase inhibitors, the second learning event showed an elevated expression of GAPDH implying a higher metabolic demand. Furthermore, we observe HRas to be a putative factor for binding/integrating two such memories. Global blockade of de novo protein synthesis during encoding phase of second learning resulted in generalization of two contextual memories suggesting discrimination of two similar contexts require protein synthesis.