Karl H Obrietan
Ohio State University, OH·Neuroscience
Many brain functions rise and fall on a roughly 24-hour (circadian) cycle, including mood, memory and decision-making. A master clock in the suprachiasmatic nucleus (SCN), a small brain region, sets the timing of secondary clocks elsewhere in the brain.
- Fields
Neuroscience
Physiology
- Topics
circadian rhythms
circadian clock
suprachiasmatic nucleus
- Grants
- 2 known grants, through Apr 2031
What they work on
- Test whether circadian clocks in cortico-limbic cells run autonomously and use the core transcription-translation feedback loop (TTFL), using transgenic mice and AAV-based genetic tools.
- Examine how the CREB/CRE signaling pathway entrains and regulates cortico-limbic clocks, and use two-photon imaging in living mice to profile clock timing within these circuits.
- Test how circadian clock timing shapes plasticity-associated signaling pathways that support memory formation in cortico-limbic circuits.
- Determine how amyloid beta (Aβ) oligomers affect clock timekeeping in cultured SCN, cortical and hippocampal neurons and in brain-slice explants.
- Profile clock phase, amplitude and synchrony in the cortex and hippocampus of 5XFAD Alzheimer's model mice with cranial-window multiphoton imaging, alongside clock-gene and transcriptomic profiling.
- Test whether the clock-enhancing compound PF-670462 resynchronizes cortico-limbic oscillators in 5XFAD mice and whether this underlies its improvement of cognition.
More about the research
Much less is known about these secondary clocks, including those in cortico-limbic circuits, the memory- and emotion-related networks of the cortex and hippocampus. Disrupted clocks contribute to several nervous-system disorders. Two mouse projects ask how these clocks work and whether their breakdown contributes to memory loss in Alzheimer's disease (AD).
Why it matters
Alzheimer's disease affects over 35 million people worldwide and has few clinical treatments. If clock desynchronization in memory circuits contributes to AD cognitive decline, restoring clock timing, for example with compounds like PF-670462, could become a new therapeutic direction. Understanding how brain clocks are built could also guide targeted chronotherapies, treatments timed to body rhythms, for other nervous-system disorders.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Martin Hruska
West Virginia University, WV·Neuroscience
Test how acute amyloid-beta affects PSD-95 stability in spines with different numbers of nanomodules. Use live-cell STED super-resolution imaging, with CRISPR tags on the neurons' own PSD-95 and AMPA receptors.
Kim Dore
University of California-San Diego, CA·Neuroscience
Measure PSD-95 palmitoylation, the fatty tag that anchors this scaffold protein in synapses, across brain regions differently affected by Alzheimer's in APP/PS1 model mice and postmortem human brain samples.
Johannes W Hell
University of California-Davis, CA·Neuroscience
Test whether norepinephrine taken into neurons by the transporters OCT3 and PMAT activates internal β2ARs to drive GluA1 phosphorylation, AMPAR surface delivery and LTP, using inhibitors, knockout mice, immunoblotting and immunofluorescence.
The school
Ohio State University: 71 labs on PI Pages, $1.6B a year on research, 882 research doctorates a year.
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