Larry Zweifel, PhD

Personal Statement

The main focus of my research efforts are to define how specific genes influence neuronal connectivity and function within neural circuits that regulate innate and motivated behaviors with a special emphasis on genes linked to psychiatric disorders such as schizophrenia and depression.

My laboratory utilizes conventional mouse genetics approaches coupled to viral-based strategies for projection specific gene manipulation, optogenetic and pharmacogenetic approaches, in vivo single unit electrophysiology recordings, whole-cell patch clamp, in vivo fiber-optic imaging, and behavior. We have recently demonstrated that a disease-related mutation in the human KCNN3 gene that encodes the calcium activated potassium channel SK3 significantly alters activity pattern regulation of midbrain dopamine neurons resulting in disruption of specific behavioral domains relevant to schizophrenia.

We have also shown that phasic activation of dopamine neurons potently influences fear processing by the amygdala and is critical for the prevention of generalized fear and anxiety. Other recent developments in the lab include the identification of CRF neurons in the central amygdala as key regulators of cued fear memory acquisition and the identification of a novel dopaminergic pathway within the hypothalamus that regulates social behavior.

Education

Ph.D. Neuroscience 2005, John Hopkins University
B.S. Biochemistry 1997, University of Missouri

Department Affiliations

Recent Publications

A dopamine-dependent mechanism for Reward-induced modification of Fear memories.
(2024 Sep 8)
bioRxiv
Kong MS, Jo YS, Sethi E, Pyeon GH, Zweifel LS

Dynorphin modulates motivation through a pallido-amygdala cholinergic circuit.
(2024 Jul 31)
bioRxiv
Sun Q, Liu M, Guan W, Xiao X, Dong C, Bruchas MR, Zweifel LS, Li Y, Tian L, Li B

Distinct dynamics and intrinsic properties in ventral tegmental area populations mediate reward association and motivation.
(2024 Sep 24)
Cell Rep 43(9): 114668
Elum JE, Szelenyi ER, Juarez B, Murry AD, Loginov G, Zamorano CA, Gao P, Wu G, Ng-Evans S, Yee JX, Xu X, Golden SA, Zweifel LS

Corticotropin-Releasing Factor Release From a Unique Subpopulation of Accumbal Neurons Constrains Action-Outcome Acquisition in Reward Learning.
(2024 Aug 22)
Biol Psychiatry
Eckenwiler EA, Ingebretson AE, Stolley JJ, Fusaro MA, Romportl AM, Ross JM, Petersen CL, Kale EM, Clark MS, Schattauer SS, Zweifel LS, Lemos JC

An arginine-rich nuclear localization signal (ArgiNLS) strategy for streamlined image segmentation of single cells.
(2024 Aug 6)
Proc Natl Acad Sci U S A 121(32): e2320250121
Szelenyi ER, Navarrete JS, Murry AD, Zhang Y, Girven KS, Kuo L, Cline MM, Bernstein MX, Burdyniuk M, Bowler B, Goodwin NL, Juarez B, Zweifel LS, Golden SA

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