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 dorsal hippocampus-prodynorphinergic dorsolateral septum-to-lateral hypothalamus circuit mediates contextual gating of feeding.
(2026 Feb 12)
Neuron
Goode TD, Bernstein MX, Totty MS, Alipio JB, Vicidomini C, Pathak D, Besnard A, Chizari D, Sachdev N, Kritzer MD, Chung A, Duan X, Macosko E, Hicks SC, Zweifel LS, Sahay A

Neuron-specific modulation of SLC30A10 identifies dopaminergic and glutamatergic neurons as targets of manganese-induced motor disease.
(2026 Feb 10)
Proc Natl Acad Sci U S A 123(6): e2515785123
Grant SM, Melkote A, Bernstein MX, Jursa T, Taylor CA, Hutchens S, Shawlot W, Zweifel LS, Gonzales RA, Smith DR, Mukhopadhyay S

A neural circuit basis for reward-induced suppression of fear generalization and enhancement of fear extinction.
(2026 Jan 27)
Proc Natl Acad Sci U S A 123(4): e2522768123
Jo YS, Kong MS, Sethi E, Pyeon GH, Zweifel LS

GABA-glutamate corelease is a mechanism for state-dependent neurotransmission.
(2025 Nov 19)
bioRxiv
Warlow SM, Dowlat DS, Hollon NG, Faget L, Oriol L, Zell V, Zweifel LS, Hnasko TS

Differential increase in endocannabinoid levels at the plasma and intracellular membranes.
(2025 Nov 21)
iScience 28(11): 113873
Singh S, English A, Yu J, Sarroza D, Zweifel L, Bruchas MR, Land BB, Vivas O, Stella N

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