In June, we hosted the 8th Annual BRAIN Initiative Meeting. I relish this yearly event as an opportunity to celebrate and reflect on the incredible progress from this foundational Initiative as we anticipate the next set of discoveries and innovations. Planning this meeting is an enormous exercise logistically. I am deeply grateful for the tireless efforts of the NIH staff and program committee who made it not only possible, but also successful despite all the curveballs thrown at us by the ongoing COVID-19 pandemic. Diversity of the science being studied, the people doing the work, and the approaches being used are all drivers for shaping a meaningful agenda. If you missed the meeting or wish to re-watch any sessions, all meeting presentations are publicly viewable until June 2023 (register here to view them).
In this message, I’ll focus on this year’s three plenary talks, which each highlighting new frames for neuroscience research: complex interactions involved in chronic itch, cells and circuits underpinning spatial representations, and new technologies that one day may lead to new cures for neuropsychiatric disorders. These inspiring talks showcase the diversity of the BRAIN research portfolio and point to new areas for BRAIN research.
Beyond BRAIN: A new culprit for chronic itch
Pain and itch are widespread and serve an important biological function: to guide protective behavior. But we know that chronic forms of these and other conditions can incur significant suffering for millions of people. For example, atopic dermatitis affects about 15% of children worldwide, half of whom go on to develop food allergies, allergic rhinitis, and asthma: a physiological progression known as the “atopic march.” In the meeting’s first plenary lecture, Dr. Diana Bautista from the University of California, Berkeley, shared a story of scientific discovery using a modified version of a mouse model for atopic dermatitis. This work expands the mechanistic basis for chronic itch through a set of discoveries that revealed an unexpected role of chemokine signaling between neutrophils and neurons leading to skin hyperinnervation and then itch-evoked scratching. Interestingly, molecular changes in response to chronic itch reverberate throughout the spinal cord and brain and even as far as the lungs, which share common sensory ganglia with the skin.
This mouse model closely mimics chronic itch in humans, meaning there are immediate next steps for translating this work, hints of which lie in the discovery that neutrophil depletion in mice significantly attenuates chronic itch. Bautista’s work also highlights the importance of understanding how the brain and central nervous system more generally interact with the periphery. Watch Bautista’s talk.
Beyond BRAIN: Dissecting memory in primates
Our second plenary lecture focused on memory formation and retrieval: an area of significant interest to scientists, psychologists, and others. An already intriguing topic was made more so by Dr. Elizabeth Buffalo of the University of Washington School of Medicine in Seattle. Buffalo described in careful detail her innovative BRAIN-funded work about the role of memory in understanding and navigating our surroundings. The context for Buffalo’s work draws from the 2014 Nobel prize-winning discovery of grid cells, which allow the brain to map physical space. This work in rodents showed that the hippocampus and entorhinal cortex enable a rat to know where it is and revealed a network of cells underlying spatial representation in the brain. Buffalo described her group’s latest findings on the nature of such representations in the macaque brain while monkeys performed spatial navigation tasks, demonstrating for the first time a link – in primates – between visual exploration and visual spatial representation.
By performing large-scale recordings in monkeys and now extending their studies to humans, Buffalo and her team hope to develop an understanding of the circuits that support rapid learning in humans. The theories developed from this work may have implications for many diseases for which memory impairment is a hallmark, such as temporal lobe epilepsy, Alzheimer's disease, depression, and schizophrenia. Watch Buffalo’s talk.
Beyond BRAIN: Editing neural circuits
Finally, we heard about fascinating new work from Duke University’s Dr. Kafui Dzirasa, who is also a member of the BRAIN Initiative’s Multi-Council Working Group. As an engineer, psychiatrist, and physician scientist with family members living with difficult neuropsychiatric disorders, Dzirasa’s BRAIN-funded research combines scientific ingenuity with an urgency to help patients as soon as possible. His talk walked us through a novel experimental journey toward the ultimate goal of preventing neuropsychiatric conditions like depression and anxiety by predicting risk. He first described his team’s efforts to construct in rodents a stress vulnerability network or “electome” based on patterns of electrical activity. They then modeled the electome associated with major depression and used this information to modulate the circuit to promote resilience. Dzirasa then talked about his trainees’ work on using a clever protein engineering approach to modify or “edit” circuits in vivo by targeting neurons with engineered connexin protein subunits – the building blocks of ion-conducting gap junctions. Because the gap junction channels were designed to conduct in a physiologically relevant range for humans, translating this work one day may provide a way to modulate circuit activity in people with brain disorders. Watch Dzirasa’s talk.
Beyond the topics I discussed above, many offerings at this year’s meeting included using integrated data sets and FAIR data practices, neural mechanisms of internal states, quantifying behavior, various topics in neuroethics, and two sessions featuring the future of brain science: our trainees. Finally, you won’t want to miss the announcement of this year’s Show us Your BRAINs! Contest – always a fun way to celebrate the unity of science and art.
This year’s BRAIN Initiative Meeting showed us that discovery is not limited to body organs, scientific disciplines, or technologies – new frames of reference provide a fresh look at the tough problems we are trying to solve. Indeed, this has been a driving force behind the BRAIN Initiative, one that I am confident will continue to accelerate the pace of discovery and build bridges to cures. I look forward to sharing and celebrating even more groundbreaking work when we meet again at next year’s meeting – hopefully in person!
With respect and gratitude,
John Ngai, Ph.D.
Director, NIH BRAIN Initiative