ELUCIDATING CIRCUIT MECHANISMS OF BRAIN RHYTHMS IN THE AGING BRAIN - PROJECT SUMMARY BRAIN RHYTHMS COORDINA…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG073507_075
- FAIN
- R00AG073507
- Recipient
- RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $493,020
- Period
- Aug 8, 2024 – May 31, 2027
- Fiscal year
- 2024
- Place of performance state
- NY
- Source file
- FY2024_All_Assistance_Full_20261006.zip
Description
ELUCIDATING CIRCUIT MECHANISMS OF BRAIN RHYTHMS IN THE AGING BRAIN - PROJECT SUMMARY BRAIN RHYTHMS COORDINATE THE ACTIVITIES OF THOUSANDS OF NEURONS ACROSS MULTIPLE BRAIN AREAS FOR COMPLEX COGNITIVE FUNCTIONS. THE HIPPOCAMPAL THETA (4-12 HZ) RHYTHM, FOR INSTANCE, IS NOT ONLY IMPORTANT FOR INFORMATION CODING DURING LEARNING AND MEMORY, BUT ALSO ASSOCIATED WITH MEMORY DYSFUNCTIONS IN AGING AND ALZHEIMER'S DISEASE (AD). HOWEVER, THE ANATOMICAL ORIGIN AND RELATED CIRCUITRY THAT CONTROL THETA RHYTHMS REMAIN LARGELY UNKNOWN. IN THIS PROPOSAL, I SEEK TO ESTABLISH THE ROLE OF THE SUPRAMAMMILLARY NUCLEUS (SUM), AN UNDERSTUDIED HYPOTHALAMIC STRUCTURE, AS A KEY MODULATOR OF HIPPOCAMPAL THETA OSCILLATIONS, ELUCIDATE THE LINK BETWEEN STRUCTURAL AND PHYSIOLOGICAL CHANGES OF THE SUM CIRCUITRY AND MEMORY DEFICIENCY, AND DEVELOP MINIMALLY INVASIVE SUM STIMULATION STRATEGIES FOR TRANSCRANIAL THETA ENTRAINMENT AND COGNITIVE RESERVE ENHANCEMENT IN AD ANIMALS. MY PRELIMINARY DATA HAVE SHOWN THAT OPTOGENETIC STIMULATION OF THE SUM ROBUSTLY INDUCES HIPPOCAMPAL THETA OSCILLATIONS. FURTHERMORE, THE ENTRAINED THETA RHYTHM SIGNIFICANTLY ENHANCES ANIMALSâ LEARNING EFFICIENCY IN A HIPPOCAMPAL-DEPENDENT SPATIAL MEMORY TASK. THESE RESULTS SUGGEST THE SUM TO BE A PREVIOUSLY UNKNOWN HYPOTHALAMIC THETA MODULATOR AND A POTENTIAL TARGET FOR THERAPEUTIC STRATEGIES TO PREVENT OR REVERSE MEMORY IMPAIRMENT. THIS PROPOSAL IS AIMED TO GAIN A MECHANISTIC UNDERSTANDING OF THE SUM AND ITS CIRCUITRY BY TAKING ADVANTAGE OF A RECENTLY DEVELOPED TRANSGENIC (SUM-CRE) MOUSE THAT PROVIDES GENETIC ACCESS TO THE SUM AND AN ARRAY OF MODERN NEURONAL RECORDING AND MANIPULATION TECHNIQUES. IN THE K99 PHASE, I WILL DISSECT THE SUM-HIPPOCAMPAL CIRCUITS, PROBE THEIR PHYSIOLOGICAL ROLES IN HIPPOCAMPAL THETA OSCILLATION, AND ELUCIDATE HOW THEY GLOBALLY RESHAPE HIPPOCAMPAL CODING FOR MEMORY PROCESSING (AIM 1). I WILL FURTHER IDENTIFY HOW AGING MODIFIES THE STRUCTURE, PHYSIOLOGY AND FUNCTION OF THE SUM CIRCUITRY, LEADING TO OSC