Tonic activin signaling shapes cellular and synaptic properties of CA1 neurons mainly in dorsal hippocampus

Abstract

Dorsal and ventral hippocampus serve different functions in cognition and affective behavior, but the underpinnings of this diversity at the cellular and synaptic level are not well understood. We found that the basal level of activin A, a member of the TGF-β family, which regulates hippocampal circuits in a behaviorally relevant fashion, is much higher in dorsal than in ventral hippocampus. Using transgenic mice with a forebrain-specific disruption of activin receptor signaling, we identified the pronounced dorsal-ventral gradient of activin A as a major factor determining the distinct neurophysiologic signatures of dorsal and ventral hippocampus, ranging from pyramidal cell firing, tuning of frequency-dependent synaptic facilitation, to long-term potentiation (LTP), long-term depression (LTD), and de-potentiation. Thus, the strong activin A tone in dorsal hippocampus appears crucial to establish cellular and synaptic phenotypes that are tailored specifically to the respective network operations in dorsal and ventral hippocampus.