Cellular components and circuitry of the presubiculum and its functional role in the head direction system.

Orientation in space is a fundamental cognitive process relying on brain-wide neuronal circuits. Many neurons in the presubiculum in the parahippocampal region encode head direction and each head direction cell selectively discharges when the animal faces a specific direction. Here, we attempt to link the current knowledge of afferent and efferent connectivity of the presubiculum to the processing of the head direction signal. We describe the cytoarchitecture of the presubicular six-layered cortex and the morphological and electrophysiological intrinsic properties of principal neurons and interneurons. While the presubicular head direction signal depends on synaptic input from thalamus, the intra- and interlaminar information flow in the microcircuit of the presubiculum may contribute to refine directional tuning. The interaction of a specific interneuron type, the Martinotti cells, with the excitatory pyramidal cells may maintain the head direction signal in the presubiculum with attractor-like properties.

Activity dependent feedback inhibition may maintain head direction signals in mouse presubiculum.

Orientation in space is represented in specialized brain circuits. Persistent head direction signals are transmitted from anterior thalamus to the presubiculum, but the identity of the presubicular target neurons, their connectivity and function in local microcircuits are unknown. Here, we examine how thalamic afferents recruit presubicular principal neurons and Martinotti interneurons, and the ensuing synaptic interactions between these cells. Pyramidal neuron activation of Martinotti cells in superficial layers is strongly facilitating such that high-frequency head directional stimulation efficiently unmutes synaptic excitation. Martinotti-cell feedback plays a dual role: precisely timed spikes may not inhibit the firing of in-tune head direction cells, while exerting lateral inhibition. Autonomous attractor dynamics emerge from a modelled network implementing wiring motifs and timing sensitive synaptic interactions in the pyramidal-Martinotti-cell feedback loop. This inhibitory microcircuit is therefore tuned to refine and maintain head direction information in the presubiculum.

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

The presubiculum (PrS) is part of an interconnected network of distributed brain regions where individual neurons signal the animals heading direction. PrS sends axons to medial entorhinal cortex (MEC), it is reciprocally connected with anterior thalamic nuclei (ATNs), 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 PrS, which corresponds to layer IV. The physiology of LMN projecting, pyramidal neurons stood out with a tendency to fire in bursts of action potentials (APs) 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 PrS and may be engaged differently in transmitting head direction related information.