Functional differentiation of dorsal and… (R21MH138919) – Project Grant to University Of Texas At Austin

Abstract: In the RAT hippocampus (HPC), memories are thought to be coded by coordinated sequences of "place cells", neurons with receptive fields in specific spatial locations. During active behaviors, place cells representing successive locations within learned trajectories fire as organized sequences within cycles of the theta rhythm (~8 HZ). Place cell sequences that fire during active exploratory behaviors later reactivate or "replay" in a temporally compressed manner during awake rest and slow-wave sleep. Replay is thought to play a key role in memory consolidation and retrieval by transferring a compressed memory format from the HPC to downstream cortical regions that control memory-guided behaviors. Theta-coordinated place cell sequences and replay are widely believed to be important neuronal population mechanisms underlying HPC memory encoding, consolidation, and retrieval. Yet, prior studies of theta-coordinated place cell sequences and replay have focused on spatial memory operations in the dorsal HPC (dhpc). Whether coordinated place cell sequences emerge in populations of ventral HPC (vhpc) place cells remains an open question. IT is also unknown whether vhpc place cell sequence replay occurs during sleep and rest. Moreover, the extent to which coordinated place cell populations in dhpc and vhpc integrate unchanging non-spatial information, such as emotional or motivational context, across different spatial locations remains largely unexplored. This project will address these critical gaps in knowledge by testing two overarching hypotheses. The first hypothesis emerges from prior studies of individual place cells and posits that coordinated place cell sequences in both dhpc and vhpc code specific spatial trajectories at different spatial scales. An alternate hypothesis is that coordinated sequences of dhpc place cells code specific spatial locations whereas vhpc place cell populations integrate shared motivational and emotional contexts across different spatial locations. The proposed experiments combine state-of-the-art neurophysiological methods for recording dhpc and vhpc place cell populations in freely behaving rats with sophisticated analytical methods for decoding place cell sequence representations. Experiments in aim 1 will determine whether theta-coordinated sequences of place cells code longer trajectories in vhpc than in dhpc. Aim 1 will also test whether vhpc, but not dhpc, place cell populations integrate shared motivational or emotional information across different locations. Experiments in aim 2 will test whether sequences of place cells replay representations of longer trajectories in vhpc than in dhpc. Aim 2 will also test the novel hypothesis that vhpc replay integrates representations of different spatial locations that share the same emotional or motivational context, while dhpc replay separates representations of different spatial locations that share the same nonspatial context. Results from this project will reveal whether dhpc and vhpc place cell populations differentially encode, consolidate, and retrieve spatial and nonspatial components of memories. Results will thereby produce a more comprehensive understanding of HPC mechanisms and function.

Action	Obligated	Date
Amendment	$192,960	Jan 21, 2026
Original award	$232,183	Jan 13, 2025

Functional differentiation of dorsal and ventral hippocampal place cell populations

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