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.


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

Department Affiliations

Recent Publications

P2X(7) receptor-dependent increase in endocannabinoid 2-arachidonoyl glycerol production by neuronal cells in culture: Dynamics and mechanism.
(2024 Apr 6)
Br J Pharmacol
Singh S, Sarroza D, English A, Whittington D, Dong A, Malamas M, Makriyannis A, van der Stelt M, Li Y, Zweifel L, Bruchas MR, Land BB, Stella N

Pathogenic gating pore current conducted by autism-related mutations in the Na(V)1.2 brain sodium channel.
(2024 Apr 9)
Proc Natl Acad Sci U S A 121(15): e2317769121
Eltokhi A, Lundstrom BN, Li J, Zweifel LS, Catterall WA, Gamal El-Din TM

Mesoaccumbal glutamate neurons drive reward via glutamate release but aversion via dopamine co-release.
(2024 Feb 7)
Neuron 112(3): 488-499.e5
Warlow SM, Singhal SM, Hollon NG, Faget L, Dowlat DS, Zell V, Hunker AC, Zweifel LS, Hnasko TS

Pharmacological Characterization of the Endocannabinoid Sensor GRAB(eCB2.0).
(2023 Dec 8)
Cannabis Cannabinoid Res
Singh S, Sarroza D, English A, McGrory M, Dong A, Zweifel L, Land BB, Li Y, Bruchas MR, Stella N

A cluster of neuropeptide S neurons regulates breathing and arousal.
(2023 Dec 18)
Curr Biol 33(24): 5439-5455.e7
Angelakos CC, Girven KS, Liu Y, Gonzalez OC, Murphy KR, Jennings KJ, Giardino WJ, Zweifel LS, Suko A, Palmiter RD, Clark SD, Krasnow MA, Bruchas MR, de Lecea L

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