We use multi-disciplinary approaches in electrophysiology, neuromodulation (chemogenetics and optogenetics), behavioral analysis, molecular and cellular biology, protein biochemistry, and organ physiology to probe the mechanisms and relevance of signaling pathways that impact the excitability of cells in the heart and brain.

A long-standing interest of our lab has been the G protein-gated inwardly-rectifying potassium/K+ channel, or GIRK channel. GIRK channels are key determinant of excitability in the heart and central nervous system. GIRK channels expressed in the heart mediate the impact of the parasympathetic nervous system on heart rate and rhythm. GIRK channels expressed in neurons have been implicated in addiction- and mood-related behaviors, learning and memory, pain perception, and opioid analgesia. Our ongoing work seeks to characterize and exploit the molecular diversity within the GIRK channel family, identify factors that modulate GIRK channel activity, evaluate the contributions made by GIRK channels to organ physiology and behavior, and understand how experience alters the strength of GIRK-dependent signaling. If we can understand how experience drives the plasticity of GIRK-dependent signaling, and the implications of GIRK channel activity to behavior, we may be able to prevent or reverse adaptations that underlie neurological disorders such as anxiety, addiction, and pain. The recent development and characterization of small-molecule modulators of defined GIRK channel subtypes affords opportunities to explore translational applications for our pre-clinical efforts. Please check out some of our recent publications in this area:

GIRK channel activity in dopamine neurons of the ventral tegmental area bi-directionally regulates behavioral sensitivity to cocaine. McCall NM, Marron Fernandez de Velasco E, Wickman K. J Neurosci. 2019 May 8;39(19):3600-3610.

Inhibition of Pyramidal Neurons in the Basal Amygdala Promotes Fear Learning. Tipps M, Marron Fernandez de Velasco E, Schaeffer A, Wickman K. eNeuro. 2018 Oct 31;5(5).

Atrial GIRK Channels Mediate the Effects of Vagus Nerve Stimulation on Heart Rate Dynamics and Arrhythmogenesis. Lee SW, Anderson A, Guzman PA, Nakano A, Tolkacheva EG, Wickman K. Front Physiol. 2018 Jul 19;9:943.

Suppression of inhibitory G protein signaling in forebrain pyramidal neurons triggers plasticity of glutamatergic neurotransmission in the nucleus accumbens core. Marron Fernandez de Velasco E, Carlblom N, Xia Z, Wickman K. Neuropharmacology. 2017 May 1;117:33-40.

G Protein-Gated K+ Channel Ablation in Forebrain Pyramidal Neurons Selectively Impairs Fear Learning. Victoria NC, Marron Fernandez de Velasco E, Ostrovskaya O, Metzger S, Xia Z, Kotecki L, Benneyworth MA, Zink AN, Martemyanov KA, Wickman K. Biol Psychiatry. 2016 Nov 15;80(10):796-806.

Selective Ablation of GIRK Channels in Dopamine Neurons Alters Behavioral Effects of Cocaine in Mice. McCall NM, Kotecki L, Dominguez-Lopez S, Marron Fernandez de Velasco E, Carlblom N, Sharpe AL, Beckstead MJ, Wickman K. Neuropsychopharmacology. 2017 Feb;42(3):707-715.

GIRK Channels Modulate Opioid-Induced Motor Activity in a Cell Type- and Subunit-Dependent Manner. Kotecki L, Hearing M, McCall NM, Marron Fernandez de Velasco E, Pravetoni M, Arora D, Victoria NC, Munoz MB, Xia Z, Slesinger PA, Weaver CD, Wickman K. J Neurosci. 2015 May 6;35(18):7131-42.

Mechanisms underlying the activation of G-protein-gated inwardly rectifying K+ (GIRK) channels by the novel anxiolytic drug, ML297. Wydeven N, Marron Fernandez de Velasco E, Du Y, Benneyworth MA, Hearing MC, Fischer RA, Thomas MJ, Weaver CD, Wickman K. Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10755-60

We are also utilizing powerful approaches in neuromodulation (chemogenetics and optogenetics) and in vivo recordings to understand the circuit and neuronal basis of complex behaviors. As part of this work, we have invested heavily in the development of viral vectors that can be used to sample and manipulate neuronal activity, in a brain region- and neuron-specific manner. Our investment prompted us to establish the University of Minnesota Viral Vector and Cloning Core, service core that offers a convenient and low-cost option for custom viral vector development and production to investigators at the University of Minnesota and elsewhere.

Complete listing of publications authored or co-authored by Dr. Wickman