New research from NYU Langone Health has identified how specific brain cell networks help stabilize memory formation. The study, published in Science on October 30, focused on the interaction between the entorhinal cortex and the CA3 region of the hippocampus in mice. Researchers found that signaling pathways connecting these two regions play a key role in encoding spatial memories.
Previous studies have shown that the entorhinal/hippocampal circuit is essential for both forming and recalling memories, particularly by completing patterns from partial cues. Stable recall depends on maintaining consistent hippocampal place maps, even as environments change. According to the study authors, disruptions in CA3 neural computations can result in symptoms similar to those seen in schizophrenia or post-traumatic stress disorder, where memory stability and precision are compromised.
“Our study, by focusing on the stability of hippocampal representations, fills in a substantial gap in the understanding of how long-range inputs control neuronal circuits essential for memory recall,” said senior study author Jayeeta Basu, PhD, an assistant professor at NYU Langone Health.
“A better understanding of circuits supporting place maps may guide the future design of more precise treatments for conditions that affect memory,” added Dr. Basu.
The researchers investigated how neurons with long extensions coordinate activity across distant brain regions during learning. They determined that two types of long-range extensions from the lateral entorhinal cortex to CA3—excitatory glutamatergic (LECGLU) and inhibitory GABAergic (LECGABA)—signal together to stabilize learning networks. LECGLU increases excitation while also triggering “feed-forward” inhibition to fine-tune firing; LECGABA suppresses local inhibition to encourage CA3 activity. This combined effect supports stable recurrent activity needed for encoding spatial memories.
“This work dissected the mechanism whereby the brain boosts excitation of brain cells to pay more attention to certain sensory information by dialing down inhibition in key microcircuits,” said first author Vincent Robert, PhD. “The team detailed a circuit mechanism that fine-tunes the dialogue among excitation, inhibition, and disinhibition in service of context-dependent memory formation and place map stability.”
The research was conducted by scientists from NYU Langone Health’s Departments of Psychiatry and Neuroscience along with collaborators from University of Texas at Austin and Imperial College London. Funding came from several National Institutes of Health grants as well as support from organizations including McKnight Scholar Award in Neuroscience, Klingenstein-Simons Fellowship Award in Neuroscience, Alzheimer’s Association Research Grant to Promote Diversity, Sloan Research Fellowship, Mathers Foundation Award, Whitehall Foundation Research Grant, American Epilepsy Society Junior Investigator Research Award, Blas Frangione Young Investigator Research Grant from New York University, Leon Levy Foundation Award, Young Researchers Bettencourt Prize, and Emerald Foundation.
NYU Langone Health is recognized for its integrated health system focused on quality care outcomes. Vizient has ranked it No. 1 among comprehensive academic medical centers nationwide for four consecutive years. U.S. News & World Report recently named four clinical specialties at NYU Langone No. 1 nationally. The system operates seven inpatient locations and over 320 outpatient sites across New York and Florida while also running two tuition-free medical schools.
