Differential involvement of CA2 in internally vs. externally driven hippocampal sequences

MacDonald and Tonegawa (1) show that inhibiting projections from dorsal CA2 to CA1 impairs performance on a delayed spatial alternation task and destabilizes sequences of neural activity in CA1 (Fig. 1). Notably, the effect on behavior is only observed if CA2 inputs are inhibited during the delay, and the effect on activity sequences is stronger for the delay compared to track running. Fig. 1. MacDonald and Tonegawa (1) report a delay-specific disruption in dorsal CA1 sequential firing and associated impairments in behavioral performance upon optogenetic inhibition of dorsal CA2 inputs. They conclude that CA2 contributes to representing the flow of time within the hippocampal network. However, in the task employed, mice do not need to keep track of time. An alternative interpretation for these results as … [↵][1]1To whom correspondence may be addressed. Email: andrew.lehr{at}phys.uni-goettingen.de or tristan.stoeber{at}posteo.net. [1]: #xref-corresp-1-1