Killam Seminar Series: Resolving the neuropeptide modulation of the midbrain dopamine system

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Larry Zweifel

Professor, Psychiatry, University of Washington, USA

Host: Jean-Francois Cloutier

Abstract: Dopamine producing neurons of the ventral midbrain play an essential role in regulating reinforcement learning and motivation. Numerous neurotransmitters and neuropeptides regulate the function of midbrain dopamine neurons, but how these transmitters and peptides coordinate to optimize the function of dopaminergic cells is not well resolved. I will describe our efforts to map the sources of neurotransmitters and neuropeptides to the ventral midbrain and to define the genetic heterogeneity of cell types within this brain region. I will discuss how viral delivery of the CRISRP/Cas9 system to specific cell types can be used to resolve the function of specific neurotransmitter and neuropeptide inputs to the ventral midbrain and the functionality of specific neuropeptide-associated signaling pathways in the modulation of dopamine neuron function.

Bio: 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

Supported by the generosity of the Killam Trusts, the MNI's Killam Seminar Series invites outstanding guest speakers whose research is of interest to the scientific community at the MNI and McGill University.