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 pharmacogentic 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


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

Department Affiliations

Recent Publications

CRISPR/SaCas9 mutagenesis of stromal interaction molecule 1 in proopiomelanocortin neurons increases glutamatergic excitability and protects against diet-induced obesity.
(2022 Nov 25)
Mol Metab 66(): 101645
Qiu J, Bosch MA, Stincic TL, Hunker AC, Zweifel LS, Rønnekleiv OK, Kelly MJ

The effect of selective nigrostriatal dopamine excess on behaviors linked to the cognitive and negative symptoms of schizophrenia.
(2022 Nov 15)
Moya NA, Yun S, Fleps SW, Martin MM, Nadel JA, Beutler LR, Zweifel LS, Parker JG

Distinct Encoding of Reward and Aversion by Peptidergic BNST Inputs to the VTA.
Front Neural Circuits 16(): 918839
Soden ME, Yee JX, Cuevas B, Rastani A, Elum J, Zweifel LS

Disinhibitory feedback loops for reward and aversion.
(2022 Feb)
Cell Res 32(2): 115-116
Juarez B, Zweifel LS

Autism-associated mutations in K(V)7 channels induce gating pore current.
(2021 Nov 9)
Proc Natl Acad Sci U S A 118(45):
Gamal El-Din TM, Lantin T, Tschumi CW, Juarez B, Quinlan M, Hayano JH, Li J, Zweifel LS, Catterall WA

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