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

Temporal scaling of dopamine neuron firing and dopamine release by distinct ion channels shape behavior.
(2023 Aug 11)
Sci Adv 9(32): eadg8869
Juarez B, Kong MS, Jo YS, Elum JE, Yee JX, Ng-Evans S, Cline M, Hunker AC, Quinlan MA, Baird MA, Elerding AJ, Johnson M, Ban D, Mendez A, Goodwin NL, Soden ME, Zweifel LS

A cortico-amygdala neural substrate for endocannabinoid modulation of fear extinction.
(2023 Jul 19)
Neuron
Gunduz-Cinar O, Castillo LI, Xia M, Van Leer E, Brockway ET, Pollack GA, Yasmin F, Bukalo O, Limoges A, Oreizi-Esfahani S, Kondev V, Báldi R, Dong A, Harvey-White J, Cinar R, Kunos G, Li Y, Zweifel LS, Patel S, Holmes A

Dopamine D2 receptors in the bed nucleus of the stria terminalis modulate alcohol-related behaviors.
(2023 Jun 14)
bioRxiv
Pati D, Lee SI, Conley SY, Sides T, Boyt KM, Hunker AC, Zweifel LS, Kash TL

Circuit coordination of opposing neuropeptide and neurotransmitter signals.
(2023 Jul)
Nature 619(7969): 332-337
Soden ME, Yee JX, Zweifel LS

Cocaine Seeking And Taking Are Oppositely Regulated By Dopamine.
(2023 Apr 10)
bioRxiv
Burgeno LM, Farero RD, Murray NL, Panayi MC, Steger JS, Soden ME, Evans SB, Sandberg SG, Willuhn I, Zweifel LS, Phillips PEM

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