# Transformation of Neuronal Activity in the Entorhinal-hippocampal-neocortex Path

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $612,592

## Abstract

SUMMARY
What is the right way to investigate neuronal circuits? The dominant strategy in neuroscience is
to examine the relationships between stimuli, brain signals and behavior. In this framework, the
investigator is in a privileged situation. Because s/he has access to both brain patterns and
signals outside the brain, s/he can establish correlations between them. However, without
further ‘grounding’, it remains unknown whether these experimenter-observed correlations are
actually utilized by the brain. The present project will take an alternative approach by
investigating how neuronal population patterns in an upstream circuit are ‘read out’ by a
downstream observer circuit/mechanism in memory circuits. Using this strategy, we will
investigate how neuronal activity is transformed at each stage in the entorhinal cortex (EC) –
dentate gyrus (DG) – CA2/3 – CA1- neocortex loop, and relate such transformations to
behavior. The projects will combine large-scale electrophysiology, optogenetics and imaging in
behaving rodents. Project 1 will examine the distinct contributions of medial and lateral
entorhinal cortex (MEC, LEC) to spatial versus object learning, and will link behavior to EC-DG
transmission of theta-gamma oscillatory patterns. Project 2 will examine information
transmission within the dentate gyrus and across EC-DG-CA3 synapses. We will first quantify
changes in LFP and spike-LFP coupling to test the contributions of EC and DG granule cell
input to the firing patterns of DG mossy and CA3 pyramidal cells. We will then test whether DG
granule and mossy cell replay is coordinated with hippocampal sharp wave ripples or with EC
cell assemblies during post-experience sleep. Finally, we will test whether optogenetic
manipulation of dentate spikes affects memory and induces re-configuration of CA3 networks.
Project 3 examines whether distinct neuronal trajectories, such as forward and reversed
sequences, are read out differentially by target circuits in the CA3-CA1 and CA1-parietal cortical
circuits. Finally, Project 4 will test whether different hippocampal patterns are translated to
distinct neocortical functional maps and whether such maps are modified by learning. Our
‘reader-centric’ approach will establish how neuronal patterns are transformed in the entorhinal-
hippocampal-entorhinal loop, providing critical insights into physiological mechanisms of
learning and memory and relevant diseases.

## Key facts

- **NIH application ID:** 10131264
- **Project number:** 5R01MH122391-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** GYORGY BUZSAKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $612,592
- **Award type:** 5
- **Project period:** 2020-03-20 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131264

## Citation

> US National Institutes of Health, RePORTER application 10131264, Transformation of Neuronal Activity in the Entorhinal-hippocampal-neocortex Path (5R01MH122391-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10131264. Licensed CC0.

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