John Mantsch
Medical College of Wisconsin, WI·Neuroscience
Chronic stress changes how the brain's prefrontal cortex, a region that guides decisions and self-control, does its job. That can make it harder to adapt when circumstances change, and it can push people with substance use disorders back toward drug use.
- Fields
Neuroscience
Pharmacology
Psychology
- Topics
chronic stress
cognitive flexibility
major depressive disorder
- Grants
- 2 known grants, through Oct 2029
What they work on
- Test whether chronic unpredictable stress reduces dendritic spines on D2 receptor–expressing prelimbic neurons that project to the nucleus accumbens core, causing sex-dependent set-shifting deficits in mice.
- Determine whether increased REDD1, a stress-induced protein, and disrupted mTORC1 growth signaling in prelimbic pyramidal neuron subpopulations cause stress-induced loss of cognitive flexibility.
- Examine whether disrupted actin cycling, which builds dendritic spine structure, in prelimbic cortex neuron subpopulations contributes to stress-induced cognitive inflexibility.
- Characterize how corticosterone triggers 2-AG endocannabinoid release and CB1 receptor–dependent loss of GABA inhibition in the prelimbic cortex to amplify cocaine seeking in rats.
- Identify the prelimbic cortex output pathways that mediate stress-potentiated reinstatement of cocaine seeking.
- Test whether CRF-R1 signaling in ventral tegmental area neurons projecting to the prelimbic cortex makes stress a direct relapse trigger after extended cocaine access.
More about the research
Both projects study how stress reshapes specific prefrontal neurons and their connections. One focuses on cognitive flexibility, a problem in depression. The other focuses on relapse to cocaine seeking.
Why it matters
Many people with depression and other stress-related conditions struggle with rigid thinking and rumination. Stress is also a common, unavoidable contributor to relapse in substance use disorders. By pinpointing molecules such as REDD1, mTORC1, corticosterone–endocannabinoid signaling and CRF receptors in defined brain circuits, this work could point to new drug targets. It may also help explain why stress affects some patients differently depending on their sex or how severe their addiction is.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Mary Kay Lobo
University of Maryland, Baltimore, MD·Neuroscience
Map cellular, synaptic plasticity and molecular changes in defined cell subtypes of the medial prefrontal cortex and nucleus accumbens in mice exposed to fentanyl during the equivalent of human gestation, from weaning through adolescence.
Heath Schmidt
University of Pennsylvania, PA·Neuroscience
Define how amylin receptors on specific cell types, dopamine and GABA neurons of the ventral tegmental area and D1- or D2-receptor medium spiny neurons of the nucleus accumbens, control oxycodone self-administration and relapse-like seeking, using viral gene delivery in transgenic rats.
Wendy Lynch
University of Virginia, VA·Neuroscience
Determine how doses of inhibitory and excitatory low-intensity focused ultrasound (LIFU) applied to the rat dorsomedial prefrontal cortex change markers of neuronal activity and dopamine and glutamate signaling during early and late opioid withdrawal.
The school
Medical College of Wisconsin: 17 labs on PI Pages, $360M a year on research, 44 research doctorates a year.
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