Peri-Head Distance Coding in the Mouse Brainstem

Abstract

Perceiving and representing space is essential for animals to navigate the environment, avoid threats, and interact with objects. In particular, peripersonal space (PPS) — the space immediately surrounding the body — plays a crucial role in object localization, defensive reactions, and goal-directed behaviors. Extensive research in primates has identified many cortical and subcortical regions that contain PPS representations. While prior research has focused on the reference frame transformation in PPS-representing neurons, surprisingly little is known about how distance in PPS is encoded. Here, we propose the rodent whisker system as a model for studying the neural mechanisms underlying distance encoding within PPS. By sweeping their whiskers through the space near the head, rodents extract information about object locations through mechanical signals transduced by trigeminal ganglion (TG) afferents. However, how these sensory inputs are transformed into a spatial representation of distance in the second order processing center, the brainstem, remains unclear. This dissertation investigates this question with the following three studies: (i) the first study examines how neurons in the principal trigeminal nucleus (PrV) encode object distance in peri-head space. Using in vivo electrophysiological recordings in awake, behaving mice during a naturalistic wall-passing paradigm, we discover that PrV neurons exhibit a diverse range of distance tuning properties. While some neurons show a monotonic increase in firing rate with object proximity (a "proximity code"), others exhibit non-monotonic tuning with peak activity at specific distances (a "map code"), forming a neural representation of peri-head space. (ii) The second study investigates the role of multi-whisker integration in shaping the distance representation in PrV. Through acute whisker cutting, we assess how removing multi-whisker inputs alters PrV neural responses to object distance. The results reveal that multi-whisker integration contributes substantially to but is not absolutely required for the formation of the map code in PrV. (iii) The third study explores the role of inhibitory circuits in transforming monotonic proximity-based inputs into a distance map code. Using optogenetic and chemogenetic manipulations, we selectively suppress either local or long-range inhibitory projections within PrV. The findings show that local inhibition modulates the gain of PrV firing rate without altering distance tuning, whereas long-range inhibitory inputs from the spinal trigeminal nucleus interpolaris (SpVi) to PrV play a crucial role in generating the non-monotonic map representation of object distance. Together, these studies provide novel insights into the neural mechanisms underlying the emergence of distance maps in the early tactile processing center of the brainstem. By identifying the circuit mechanisms that transform mechanical inputs into a map-like representation of peri-head distances, this work enhances our understanding of how simple neural computations in early sensory processing shape the representation of PPS in the somatosensory system.