Unlocking the Secrets of Perception: How a Newly Discovered Brain Circuit Illuminates the Path from Familiarity to Novelty
Imagine your brain has a built-in GPS that constantly updates its map based on your memories and emotions.This groundbreaking discovery, from researchers at NYU Grossman School of Medicine, reveals just such a system.Published online February 18 in Nature Neuroscience, the research unveils a previously unknown pathway in the brain that integrates sensory information, memories, and emotions to distinguish between familiar and novel stimuli, and to assess their importance. This discovery offers crucial insights into how the brain processes information and may pave the way for new treatments for neurological disorders.
The study focuses on a circuit connecting the entorhinal cortex (EC), a brain region processing sensory information, and the hippocampus (HC), the memory processing center. While an indirect pathway between these regions was already known, this research reveals a previously unrecognized direct feedback loop. This direct connection allows for the rapid tagging of sights and sounds as vital based on their context within existing memories and emotions.
“Ours is the first anatomical and functional analysis of both the new direct hippocampal-cortical feedback loop, and the indirect loop found decades ago.”
Jayeeta Basu, PhD, Assistant Professor, Department of Psychiatry and the Department of Neuroscience, NYU Langone Health
Dr. Basu, a faculty member of the Institute for Translational Neuroscience at NYU Langone Health and recipient of the Presidential Early Career Award for Scientists and Engineers, further explained that the differences in wiring, timing, and location of the two loops suggest separate but parallel roles, working together to encode complex information. “The differences we found in their wiring,timing,and location suggest that the loops have separate but parallel roles that let them work together to encode even more complex information,”
she added.
The long-established model of this circuit proposed that the HC receives sensory information from EC layers 2 and 3, but sends feedback only indirectly through EC layer 5. This indirect route introduces time lags that can alter the feedback signals. However, the current research identified a second, direct loop connecting the HC to EC layers 2 and 3, enabling memories and emotions to rapidly influence the perception of sights and sounds. This discovery addresses a long-standing paradox: the lack of a known direct pathway between the HC and the amygdala, the brain’s emotional center. The newly discovered connection to the EC may serve as a crucial link.
The study also mapped connections between brain cells based on their ability to manage charged particles, revealing key differences in the two loops. The previously known indirect loop was found to be excitatory,triggering all-or-nothing signals called action potentials. In contrast, the new direct feedback loop, in response to similar incoming signals, recruited strong inhibition, never eliciting action potentials but rather sending small depolarizing potentials. These delicate, repeated signals can combine with messages from other brain regions to facilitate more intricate computations, accelerated learning, and greater plasticity—the strengthening of connections between neurons.
Future research will explore how hippocampal output related to emotions and memories influences decision-making in the prefrontal cortex and fear coding in the amygdala. The team will also investigate changes in the direct circuit during aging and in Alzheimer’s disease in mice, seeking parallels in humans. This research, supported by numerous grants from the National Institutes of Health (NIH), the Alzheimer’s Association, and other organizations, represents a notable advancement in our understanding of brain function and holds immense potential for improving the lives of individuals affected by neurological disorders such as PTSD and autism.
The research team included Tanvi Butola (first author), Melissa Hernandez Frausto, Lulu Peng, Ariel Hairston, Cara Johnson, Margot Elmaleh, Amanda Amilcar, and Fabliha Hussain from the NYU langone Institute for Translational Neuroscience; Cliff Kentros, Stefan blankvoort, and Michael Flatset from the Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology; and Claudia Clopath from Imperial College London. Dr. Basu led an NIH BRAIN initiative project (2018-2023) with Dr. Clopath and Dr. kentros to develop the tools and models used in this study.
Exploring teh Brain’s New GPS: How a Groundbreaking Finding Differentiates Between Familiarity and Novelty
Unlocking the Mysteries of Neural Pathways: A Deep Dive with Dr. jane williams, Neuroscientist
“Your brain is more like a supercomputer than you might realize, constantly updating its internal GPS based on your experiences, memories, and emotions.” With this thought-provoking opening, let’s delve into a remarkable breakthrough in neuroscience that promises to reshape our understanding of brain function.
Senior Editor: Dr. Williams, we’re thrilled to have you here to discuss the fascinating new discovery in brain circuitry involving familiarity and novelty. Can you start by explaining the meaning of this breakthrough?
Dr. Jane Williams: Absolutely, and thank you for having me. This discovery, spearheaded by Dr. Jayeeta Basu and her team, reveals a novel brain pathway that integrates sensory information, memories, and emotions to help distinguish between familiar and novel stimuli. This pathway consists of a direct feedback loop connecting the entorhinal cortex and the hippocampus, regions previously known only to communicate indirectly. This direct connection is crucial as it enables the brain to rapidly assess and tag stimuli based on contextual memory and emotion, thus fundamentally enhancing our cognitive map, much like a live-updating GPS.
Senior Editor: The research mentions that the brain has separate pathways with distinct roles. Can you elaborate on how these pathways function and their implications for cognitive processing?
Dr.Jane Williams: Indeed, the brain’s ingenious architecture includes both a direct and an indirect feedback loop. The indirect pathway, involving the entorhinal cortexS layer 5 and older models, is longer and can introduce delays. On the other hand, the newly discovered direct loop connects the hippocampus directly to entorhinal cortex layers 2 and 3.
This direct pathway is fascinating because it leverages inhibition rather than excitation,allowing for subtler,more nuanced computations in the brain. These shifts enhance cognitive versatility, leading to improved learning and plasticity due to the rapid integration of sensory and emotional data. This dual-pathway system, with its parallel yet intertwined function, reflects the complexity and adaptability of human cognition and holds promise for understanding disorders such as PTSD and autism.
Senior Editor: Reflecting on ancient models, how does this discovery shape our understanding of the brain’s path from sensation to memory?
Dr. Jane Williams: Historically, the model was that sensory information flowed from the entorhinal cortex to the hippocampus with only an indirect feedback loop. This new discovery redefines that model by showing that direct feedback is not only possible but functional, facilitating immediate adjustments in perception and memory based on current context.
By providing a real-time channel back to the hippocampus, the brain can swiftly refine its internal representations and responses, aligning closely with evolutionary needs to quickly adapt to new environments. This mechanism is akin to a seasoned traveler who constantly refers back to a dynamic map, revising routes based on new landmarks or changes in the terrain. Such rapid recalibration is crucial for survival and efficiency.
Senior Editor: Turning our attention to potential clinical implications, what possibilities does this discovery open for brain-related disorders?
Dr. Jane Williams: This groundbreaking discovery has significant implications for neurotherapeutic strategies. By understanding how the brain distinguishes between familiarity and novelty, we can develop targeted therapies for conditions like Alzheimer’s, PTSD, and autism. Particularly for Alzheimer’s, where memory loss is paramount, identifying and possibly strengthening these direct pathways could offer new avenues for treatment.
Moreover, understanding these circuits could enhance our approaches to emotional processing in disorders such as PTSD. Clinicians could, for example, develop interventions that better train the brain to modulate responses to novel versus familiar stimuli, thus reducing fear or anxiety reactions.
Senior Editor: Looking ahead, what are the next steps for research in this area?
Dr. Jane Williams: Future research will undoubtedly focus on several key areas. One is exploring the implications of these pathways in decision-making and emotion regulation, particularly within the prefrontal cortex and the amygdala. another critical path involves studying how these circuits change with aging and in disease states like Alzheimer’s through both animal models and clinical studies.
Additionally, researchers will look to refine and expand the tools used in this discovery, including advanced neuroimaging and computational models, to further decode the intricate web of brain connections. This will not only deepen our foundational understanding but also pave the way for innovative treatments that can repair or augment these pathways.
Final Thoughts
This discovery marks an exciting chapter in neuroscience, where the nuances of brain circuitry unveil new horizons for understanding human cognition and developing treatments for neurological disorders. Your comments and insights are invaluable; please share your thoughts on how these findings might affect future research directions or therapeutic approaches in the comments below.
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