A recent study led by researchers at NYU Langone Health has uncovered brain circuits that enhance the stability of memories during learning processes. Published in the journal Science, the research indicates that activity within signaling pathways connecting the entorhinal cortex and the CA3 region of the hippocampus assists mice in encoding spatial maps in their brain circuits.
Previous research has highlighted the importance of the entorhinal-hippocampal circuit for both memory formation and retrieval, particularly through the completion of patterns based on partial cues. For reliable memory retrieval, it is crucial that the hippocampal spatial maps remain stable, maintaining some resistance to environmental changes. Disruptions in neural computations within the CA3 region can lead to symptoms akin to those seen in schizophrenia or post-traumatic stress disorder, where memory stability and accuracy deteriorate.
According to the study”s lead author, Jayeeta Basu, who serves as an assistant professor in the Departments of Psychiatry and Neuroscience at NYU Langone Health, “Our study, focused on the stability of hippocampal representations, bridges a significant gap in understanding how long-range inputs control the essential neural circuits for memory retrieval.” Basu, a faculty member at the NYU Langone Health Institute for Translational Neuroscience and a recent recipient of the Presidential Early Career Award for Scientists and Engineers, further noted that a deeper understanding of circuits supporting spatial maps could inform the design of more precise treatments for memory-affecting conditions.
This study centers around neurons, the brain”s cells that “fire” to transmit electrical signals coordinating thoughts and memories by rapidly altering their positive and negative charge balance. When an electrical charge reaches the end of a neuron”s extensions, it prompts the release of neurotransmitters that traverse the space between cells. These neurotransmitters bind to proteins that either stimulate (excite) or inhibit the activation of adjacent neurons, as described by the researchers. This interplay of excitation and inhibition creates a balance that converts noise into coherent thoughts, a balance preserved when the brain is at rest. However, during learning, increases in excitation facilitate the encoding of new memories, and neuronal activity patterns dictate the specificity of the memories formed.
The research team focused on long-extended neurons that coordinate activity across distant brain regions. Current understanding of how long-range cellular signals influence local circuits remains limited, particularly as the brain reconciles stable patterns (what is already known) with new data (from constantly changing experiences) to establish memories. The researchers determined that two types of long-range extensions from the lateral entorhinal cortex to the CA3 region send simultaneous signals to stabilize learning neural networks. Specifically, long-range excitatory glutamatergic (LECGLU) extensions and inhibitory GABAergic (LECGABA) extensions were observed to enhance the activity of interconnected neuronal groups, promoting learning.
In their study, the authors examined interactions between long-range inputs from the lateral entorhinal cortex and CA3 circuits at the individual cell level. They found that LECGLU induces excitation in CA3 but also an anterograde inhibition that modulates neuronal activity, while LECGABA suppresses this local inhibition to disinhibit (stimulate) CA3 activity. This combined action promotes stability in CA3 by triggering recurrent activity in specific circuits, thereby encoding spatial memories.
The authors noted, “This work analyzed the mechanism through which the brain increases the excitation of brain cells to pay closer attention to certain sensory information while reducing inhibition in key microcircuits.” Consequently, the team detailed a circuit mechanism that finely tunes the dialogue among excitation, inhibition, and disinhibition for context-dependent memory formation and the stability of spatial maps.
