Cooperate to compete: Identifying a potential role for hippocampal region CA2 in episodic memory formation

Abstract

To memorize an experience, our brain is replaying associated sequences of neuronal activity in the hippocamus and associated regions. Since we remember only a fraction of our experiences, the brain must have a way to prioritize certain neural activity sequences for replay. This thesis outlines why and how interactions between hippocampal region CA2 and CA3 may play a decisive role in determining which sequences are reactivated. These interactions stand out for two reasons: First, synaptic plasticity at CA3 to CA2 projections is strongly regulated by neuromodulatory substances, which are likely released during emotionally arousing situations. Second, in both directions, excitatory activity in one region suppresses activity in the other region. Connecting these findings, I argue that neuromodulatory release can lead to selective pairing of co-active neural activity sequences across the two regions. Paired sequences may support each others reactivation, while suppressing competing sequences. As shown by neural network simulations, such a pairing mechanism may be particularly beneficial for neural activity sequences comprised of few cells. As the number of recruited cells varies depending on the type of experience, the proposed CA2-CA3 sequence interaction may explain why CA2 is involved in some but not all situations.