Laminar Localization and Projection-Specific Properties of Presubicular Neurons Targeting the Lateral Mammillary Nucleus, Thalamus or Medial Entorhinal Cortex

Abstract

The presubiculum is part of an interconnected network of distributed brain regions where individual neurons signal the animals heading direction. Presubiculum sends axons to medial entorhinal cortex (MEC), it is reciprocally connected with anterior thalamic nuclei (ATN) and it sends feedback projections to the lateral mammillary nucleus (LMN), involved in generating the head direction signal. The intrinsic properties of projecting neurons will influence the pathway-specific transmission of activity. Here we used projection specific labeling of presubicular neurons to identify MEC, LMN and ATN projecting neurons in mice. MEC projecting neurons located in superficial layers II/III were mostly regular spiking pyramidal neurons, and we also identified a Martinotti-type GABAergic neuron. The cell bodies of LMN projecting neurons were located in a well-delimited area in the middle portion of the presubiculum, which corresponds to layer IV. The physiology of LMN projecting, pyramidal neurons stood out with a tendency to fire in bursts of action potentials with rapid onset. These properties may be uniquely adapted to reliably transmit visual landmark information with short latency to upstream LMN. Neurons projecting to ATN were located in layers V/VI, and they were mostly regular spiking pyramidal neurons. Unsupervised cluster analysis of intrinsic properties suggested distinct physiological features for the different categories of projection neurons, with some similarities between MEC and ATN projecting neurons. Projection-specific subpopulations may serve separate functions in the presubiculum and may be engaged differently in transmitting head direction related information.

Significance Statement The presubiculum is part of a brain wide network of head direction cells. It contributes to the generation of grid cell activity in the downstream medial entorhinal cortex, and it also feeds back information to subcortical input regions. Here we identify projection specific subpopulations of presubicular neurons. We show how they differ in their morphology, laminar location and in their electrophysiological tuning. Distinct presubicular cell types may provide specific coding capacities for distinct output channels of presubiculum.