Jerri Rook
Vanderbilt University, TN·Pharmacology
Schizophrenia involves more than hallucinations and delusions. Patients also face blunted motivation and persistent problems with attention, memory and flexible thinking, and these cognitive symptoms respond poorly to existing drugs.
- Fields
Pharmacology
Neuroscience
- Topics
schizophrenia
muscarinic acetylcholine receptor
mAChR
- Grants
- 1 known grant, through Jan 2027
What they work on
- Test whether positive allosteric modulators of the M1 muscarinic receptor induce long-term depression of excitatory synapses by acting on M1 in prefrontal cortex pyramidal cells, and whether this requires phospholipase D rather than M1 in inhibitory neurons.
- Test the hypothesis that M1 activation increases inhibitory transmission in the prefrontal cortex by directly exciting defined populations of inhibitory interneurons, using selective M1 deletion and optogenetic silencing.
- Determine which prefrontal neuronal populations must express M1 for M1 modulators to reverse deficits in specific behavioral measures of cognitive function in rodent models relevant to schizophrenia.
- Compare modulators that differentially couple M1 to phospholipase D versus phospholipase C to separate the signaling pathways underlying synaptic depression and increased inhibition.
More about the research
A promising alternative route targets acetylcholine, a chemical messenger in the brain, through its muscarinic receptors. Rather than switching these receptors on directly, the approach uses positive allosteric modulators, compounds that bind a separate site and amplify the receptor's response to the brain's own acetylcholine, which makes it possible to act on one receptor subtype and avoid side effects. The open question is mechanistic: how do these receptors actually reshape brain circuits relevant to each symptom cluster?
Why it matters
Cognitive and negative symptoms of schizophrenia are largely untreated by current antipsychotics. Pinpointing which prefrontal cortex neurons and which signaling enzymes M1 receptors must act on to restore cognitive performance could guide the design of selective muscarinic modulators, helping drug developers choose compounds most likely to improve thinking and motivation in patients with schizophrenia and related brain disorders.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Thilo Womelsdorf
Vanderbilt University, TN·Neuroscience
Determine the dose-response efficacy of an M1 muscarinic receptor positive allosteric modulator on attention, working memory, effort control, cognitive flexibility and visuospatial problem solving in monkeys, using a multi-task touchscreen battery in home-cage kiosks.
Daniel Foster
University of South Carolina-Columbia, SC·Neuroscience
Test whether M4 PAMs, drugs that boost the M4 acetylcholine receptor, reduce repetitive over-grooming in SAPAP3 knockout mice and other mouse models of repetitive behavior.
Alison Barth
Carnegie Mellon University, PA·Neuroscience
Map the circuit connections of a molecularly defined subtype of somatostatin (SST) inhibitory neurons in superficial mouse sensory cortex, and how they change during whisker-reward learning, using cell-type- and pathway-specific brain slice recordings.
The school
Vanderbilt University: 22 labs on PI Pages, $1.3B a year on research, 494 research doctorates a year.
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