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

Education

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

Department Affiliations

Recent Publications

Intercalated amygdala clusters orchestrate a switch in fear state.
(2021 May 26)
Nature
Hagihara KM, Bukalo O, Zeller M, Aksoy-Aksel A, Karalis N, Limoges A, Rigg T, Campbell T, Mendez A, Weinholtz C, Mahn M, Zweifel LS, Palmiter RD, Ehrlich I, Lüthi A, Holmes A

Central amygdala circuits in valence and salience processing.
(2021 Jul 23)
Behav Brain Res 410(): 113355
Kong MS, Zweifel LS

CRISPR knockdown of Kcnq3 attenuates the M-current and increases excitability of NPY/AgRP neurons to alter energy balance.
(2021 Mar 22)
Mol Metab 49(): 101218
Stincic TL, Bosch MA, Hunker AC, Juarez B, Connors AM, Zweifel LS, Rønnekleiv OK, Kelly MJ

Repetitive blast mild traumatic brain injury increases ethanol sensitivity in male mice and risky drinking behavior in male combat veterans.
(2021 May)
Alcohol Clin Exp Res 45(5): 1051-1064
Schindler AG, Baskin B, Juarez B, Janet Lee S, Hendrickson R, Pagulayan K, Zweifel LS, Raskind MA, Phillips PEM, Peskind ER, Cook DG

Periaqueductal gray/dorsal raphe dopamine neurons contribute to sex differences in pain-related behaviors.
(2021 Apr 21)
Neuron 109(8): 1365-1380.e5
Yu W, Pati D, Pina MM, Schmidt KT, Boyt KM, Hunker AC, Zweifel LS, McElligott ZA, Kash TL

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