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A transcriptomic axis aligns with in vivo functional dynamics in hippocampal inhibitory circuits
Hyun Choong Yong1,2,3, Stephanie A Herrlinger1, Margaret E Conde Paredes1,4
1Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University; New York, NY, USA.
Biorxiv : the Preprint Server for Biology
|April 17, 2026
Summary
This study links neuron activity to molecular identity in the mouse hippocampus using advanced imaging and spatial transcriptomics. Researchers identified distinct neuron types and their functions during navigation, revealing a transcriptomic axis of diversity.
Area of Science:
- Neuroscience
- Molecular Biology
- Genomics
Background:
- Linking molecular identity to in vivo function at single-cell resolution is a key challenge in neuroscience.
- Understanding the diversity of hippocampal interneurons is crucial for comprehending memory and navigation.
Purpose of the Study:
- To develop a pipeline linking cell-resolved in vivo imaging with spatial transcriptomics in the mouse hippocampus.
- To identify and classify hippocampal CA1 interneurons based on their physiological responses and gene expression.
Main Methods:
- Utilized a combination of cell-resolved two-photon imaging and spatial transcriptomics.
- Performed post hoc clustering of interneurons based on gene expression.
- Analyzed physiological responses during a virtual-reality navigation task.
Main Results:
- Identified 5 GABAergic subclasses and 14 distinct types of CA1 interneurons.
- Found that physiological responses aligned with a transcriptomic axis.
- Developed a classifier that predicted cell organization based on physiological features alone.
Conclusions:
- Established a scalable framework for linking in vivo circuit dynamics to cell identity.
- Revealed a transcriptomic axis encompassing structural and functional diversity of hippocampal inhibitory neurons.
- Provided a method to connect behavior to molecular identity in the hippocampus.

