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

Reductions of Grin2a in adolescent dopamine neurons confers aberrant salience and related psychosis phenotype.
(2024 Oct 28)
bioRxiv
Kielhold ML, Jacobs DS, Torrado-Pacheco A, Lebowitz JJ, Langdon AJ, Williams JT, Zweifel LS, Moghaddam B

Stress disrupts engram ensembles in lateral amygdala to generalize threat memory in mice.
(2024 Nov 12)
Cell
Lesuis SL, Park S, Hoorn A, Rashid AJ, Mocle AJ, Salter EW, Vislavski S, Gray MT, Torelli AM, DeCristofaro A, Driever WPF, van der Stelt M, Zweifel LS, Collingridge GL, Lefebvre JL, Walters BJ, Frankland PW, Hill MN, Josselyn SA

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

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