Electrophysiological properties of the medial mammillary bodies across the sleep-wake cycle

Abstract

The medial mammillary bodies (MB) play an important role in the formation of spatial memories; their dense inputs from hippocampal and brainstem regions makes them well-placed to integrate movement-related and spatial information, that is then extended to the anterior thalamic nuclei and beyond to cortex. While the anatomical connectivity of the medial MBs has been well-studied, much less is known about their physiological properties, particularly in freely-moving animals. We therefore carried out a comprehensive characterization of medial MB electrophysiology across arousal states by concurrently recording from the medial MB and the CA1 field of the hippocampus in male rats. In agreement with previous studies, we found medial MB neurons to have firing rates modulated by running speed and angular head velocity, as well as theta-entrained firing. We extended the characterization of MB neuron electrophysiology in three key ways: 1) we identified a subset of neurons (25%) that exhibit dominant bursting activity; 2) we showed that ∼30% of theta-entrained neurons exhibit robust theta cycle skipping, a firing characteristic that implicates them in a network for prospective coding of position; 3) a considerable proportion of medial MB units showed sharp wave-ripple (SWR) responsive firing (∼37%). The functional heterogeneity of MB electrophysiology reinforces their role as an integrative node for mnemonic processing and identifies potential roles for the MBs in memory consolidation through propagation of SWR-responsive activity to the anterior thalamus and prospective coding in the form of theta-cycle skipping.

Significance Statement While the medial mammillary bodies (MBs) are important for memory, it is still not clear how they support memory formation. Through conjoint medial MB and hippocampal recordings across different arousal states we identified a population of medial MB units with diverse and often conjunctive physiological properties, including theta-entrained cells, cells modulated by running speed and angular head velocity, complex bursting, theta cycle skipping activity, and hippocampal sharp-wave ripple-responsive firing. These properties likely support a role for the medial MBs in mnemonic processing, enabling the integration of separate sensory streams and the propagation of information to the thalamus.