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Diversity and sensorimotor specialization of head direction cells in the mouse thalamus

Abstract:
There is increasing recognition of diversity within functionally-defined classes of spatiallymodulated brain cells. One such functional class, the head direction (HD) cells, provides our sense of direction and is essential for spatial navigation. HD signals are routed to the cortex via the thalamus, with the highest density of HD cells found within the anterodorsal thalamic nucleus (ADn). Variability in axonal projections and in vivo firing patterns suggest the existence of distinct neuronal subpopulations in the ADn. We investigated this diversity by extracellularly recording and juxtacellularly labeling single HD cells in subregions of the ADn in awake mice. We find that in vivo firing patterns of individual HD cells are differentially modulated by light pulses, sound, and movement, indicating sensorimotor specialization. We also reveal a mediolateral gradient of calretinin-expressing (CR+) cells, with CR+ HD cells having narrower tuning widths, lower peak firing rates, and different intrinsic properties compared to CR– HD cells. We identify distinct axonal projection patterns, including HD cells innervating the thalamic reticular nucleus (TRN) and different layers of the granular retrosplenial cortex, and HD cells with additional collaterals in the dorsomedial striatum. We also define an unusual CR+ subpopulation, the tortuosa HD cells, which possess twisted dendrites and a descending axon that does not innervate the TRN. Together, these findings suggest that ADn HD cells comprise specific cell types that integrate multimodal streams of sensorimotor input within their receptive fields that relate to attention and arousal, thereby providing downstream targets with dynamically updated and behaviorally-relevant directional information.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.cub.2026.05.026

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Institution:
University of Oxford
Division:
MSD
Department:
Pharmacology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pharmacology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pharmacology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pharmacology
Role:
Author


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Funder identifier:
https://ror.org/02ymzm013
Grant:
ARUK-RF2023B-026
AVR01965
More from this funder
Funder identifier:
https://ror.org/001aqnf71
Grant:
EP/Z001358/1
More from this funder
Funder identifier:
https://ror.org/00rk2pe57
Grant:
MURI N00014-1-19-2571
More from this funder
Funder identifier:
https://ror.org/03x94j517
Grant:
MR/R011567/1
MR/Z504518/1
More from this funder
Funder identifier:
https://ror.org/01cwqze88
Grant:
F32MH139270
R01 MH120073


Publisher:
Cell Press
Journal:
Current Biology More from this journal
Publication date:
2026-06-10
Acceptance date:
2026-05-12
DOI:
EISSN:
1879-0445
ISSN:
0960-9822


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