Behavioral and circuit manipulations of directional tuning in Subiculum

NIH RePORTER · NIH · R21 · $446,627 · view on reporter.nih.gov ↗

Abstract

PROJECT SUMMARY/ABSTRACT Defining the forms of neural representation and temporal dynamics of neuron ensembles in the hippocampus and related neocortical regions such as retrosplenial and entorhinal cortex has led to a deep understanding of the brain’s ‘cognitive map’ of the environment. Such work has direct relevance to understanding the pathologies and cognitive impairments attending neurological disorders such as Alzheimer’s disease as well as intact learning and memory processes associated with navigation, episodic memory, and orienting. The dorsal subiculum is highly interconnected with these brain structures and important for normal spatial cognition, yet the unique contributions it makes to the cognitive map and flexible navigation behavior have yet to be defined. Prior work has suggested that subicular neurons are far less spatially-specific in their firing activity than those of hippocampal area CA1, a brain region forming a prominent input to subiculum. A role for subiculum in encoding and learning orientational relationships between an organism and its environment has been suggested and is consistent with its receiving input from the anterior thalamus. A major output target for subiculum is the retrosplenial cortex, a region that contains neurons with left/right turn-related activity and which has been hypothesized to form a transition of spatial cognition into action through projections to secondary motor cortex. Our project is designed to systematically investigate orientation tuning in the subiculum within environments where navigation is constrained to a network of interconnected pathways. More specifically, we will examine the question of whether individual subiculum neurons can encode multiple directions of travel as observed in preliminary data. The experiments also address context-dependence and learning in orientation tuning. The work will have implications for theories on function of the brain’s cognitive map. It is poised to identify a system by which environmental locations affording transitions between two or more directions of travel can be encoded with directional signals, which could drive left/right turning actions via outputs to retrosplenial cortex. More broadly, the project is poised to form a new direction for study of subicular function and the role of multi-directional tuning in spatial cognition.

Key facts

NIH application ID
10988639
Project number
1R21MH135321-01A1
Recipient
UNIVERSITY OF CALIFORNIA, SAN DIEGO
Principal Investigator
Douglas Arthur Nitz
Activity code
R21
Funding institute
NIH
Fiscal year
2024
Award amount
$446,627
Award type
1
Project period
2024-08-01 → 2026-07-31