Summary: A new NYU Langone-led study reveals how coordinated circuits between the entorhinal cortex and the hippocampal CA3 region stabilize memories during learning. Researchers show that synchronized excitatory and inhibitory signals from the lateral entorhinal cortex refine local CA3 activity, strengthening spatial “place maps” so that memories remain consistent even as animals acquire new information.
By balancing excitation and inhibition, these long-range inputs shape which sensory signals are prioritized and which prior memories are preserved. The findings clarify how context-dependent memories are encoded and maintained and may inform future strategies for treating disorders characterized by unstable or intrusive memories, such as PTSD and schizophrenia.
Key Facts
- Memory stability mechanism: Coordinated signaling between the lateral entorhinal cortex and CA3 stabilizes learned spatial maps in the hippocampus.
- Dual neural action: Excitatory (glutamatergic) and inhibitory (GABAergic) long-range inputs work together to tune CA3 circuits and reinforce memory representations.
- Clinical relevance: Disruption of these circuit interactions may underlie memory instability seen in conditions such as PTSD and schizophrenia.
Source: NYU Langone
Newly decoded brain circuits support memory stability during learning
Published in Science on Oct. 30, this study demonstrates that two distinct types of long-range projections from the lateral entorhinal cortex (LEC) to hippocampal CA3 act in concert to stabilize neuronal ensembles that represent places. Using cellular‑level measurements and circuit dissection in mice, the team found that LEC glutamatergic and GABAergic projections synchronize to boost and sculpt CA3 activity patterns important for encoding and retaining spatial memories.
The entorhinal–hippocampal pathway has long been recognized as essential for forming memories and for pattern completion—the brain’s ability to retrieve full memories from partial cues. Reliable recall depends on the stability of hippocampal place maps so that familiar locations and contexts remain recognizable despite some change in the environment. When CA3 computations are impaired, memory precision and stability can break down, producing maladaptive responses; for example, benign stimuli may trigger inappropriate fear by evoking traumatic memory traces.
“Focusing on the stability of hippocampal representations fills an important gap in our understanding of how long-range inputs control local circuits that are critical for memory recall,” said senior author Jayeeta Basu, PhD, assistant professor in Psychiatry and Neuroscience at NYU Langone Health. Better knowledge of these circuits could inform more targeted treatments for disorders that disrupt memory.
Repeated circuit activity sets memory templates
Neurons communicate via rapid electrical events that lead to chemical signaling across synapses. Depending on the receptors they activate, these signals drive excitation—or promote inhibition—of downstream neurons. The ongoing balance between excitation and inhibition filters neural activity, suppressing noise while allowing salient information to shape memory representations.
During learning, increases in excitation help encode new information, while the timing and pattern of activity across ensembles of neurons determine the specificity of the memory. Reactivating ensemble activity in the same pattern later evokes the stored memory and the behaviors associated with it, such as locating a reward in a particular maze.
This study focused on long-range LEC projections that contact CA3 microcircuits. The researchers identified two complementary pathways: long-range excitatory glutamatergic projections (LECGLU) and long-range inhibitory GABAergic projections (LECGABA). Together, these inputs coordinate to stabilize CA3 representations during learning.
At the single-cell level, LECGLU drives both direct excitation of CA3 neurons and feedforward inhibition that constrains excessive firing and prevents uncontrolled somatic and dendritic spikes. In contrast, LECGABA selectively suppresses that local inhibition at specific locations and compartments, effectively disinhibiting CA3 and boosting somatic output. The result is a temporally precise synergy: excitation and disinhibition cooperate to trigger recurrent CA3 activity patterns that encode stable place cells across contexts and over time.
“We dissected how the brain enhances attention to relevant sensory information by transiently dialing down inhibition in target microcircuits,” said first author Vincent Robert, PhD. “This circuit-level dialogue among excitation, inhibition, and disinhibition supports context-dependent memory formation and the stability of place maps.”
The research team includes Keelin O’Neil, Jason Moore, Shannon Rashid, Cara Johnson, and Rodrigo De La Torre from the Basu lab, along with collaborators Boris Zemelman and Claudia Clopath. The work was supported by multiple NIH grants and a range of fellowships and foundation awards.
Funding: The study was supported by several NIH grants including R01 and U01 awards, training grants, and additional support from foundations and fellowship programs in neuroscience and related fields.
Key Questions Answered:
A: They found that synchronized signals from the entorhinal cortex to hippocampus strengthen and stabilize place-based memory maps by coordinating excitation and inhibition in CA3 circuits.
A: Long-range glutamatergic inputs provide excitation and feedforward inhibition, while long-range GABAergic inputs reduce local inhibition at key compartments, together tuning circuit activity to preserve stable memory templates during learning.
A: Disruptions in these long-range and local circuit interactions can impair memory stability, a feature implicated in disorders such as PTSD and schizophrenia, suggesting potential targets for therapeutic intervention.
About this learning and memory research news
Author: Gregory Williams
Source: NYU Langone
Contact: Gregory Williams – NYU Langone
Image credit: Neuroscience News
Original research: Closed access. Title: “Cortical glutamatergic and GABAergic inputs support learning-driven hippocampal stability” by Jayeeta Basu et al., published in Science. DOI: 10.1126/science.adn0623
Abstract
Cortical glutamatergic and GABAergic inputs support learning-driven hippocampal stability
Flexibility and stability of neuronal ensembles are essential for brain function, yet how long-range inputs shape these local circuit properties is not well understood. The authors show that lateral entorhinal cortex glutamatergic (LECGLU) and GABAergic (LECGABA) projections to CA3 recruit specific microcircuits that together stabilize neuronal ensembles during learning. LECGLU provides excitation alongside feedforward inhibition that prevents runaway spiking, while LECGABA suppresses that inhibition in compartment- and pathway-specific ways to disinhibit CA3 outputs. This synergy stabilizes spatial representations as both projection types control the formation and maintenance of CA3 place cells across contexts and over time.