Caveolin-1 regulates medium spiny neuron structural and functional plasticity
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ORIGINAL INVESTIGATION
Caveolin-1 regulates medium spiny neuron structural and functional plasticity Katherine R. Tonn Eisinger 1,2,3 & Andrew D. Chapp 1 & Samuel P. Swanson 1 & Daniel Tam 1 & Natalie M. Lopresti 1,2 & Erin B. Larson 1 & Mark J. Thomas 1,2 & Lorene M. Lanier 1,2 & Paul G. Mermelstein 1,2 Received: 10 February 2020 / Accepted: 18 May 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale Caveolin-1 (CAV1) is a structural protein critical for spatial organization of neuronal signaling molecules. Whether CAV1 is required for long-lasting neuronal plasticity remains unknown. Objective and Methods We sought to examine the effects of CAV1 knockout (KO) on functional plasticity and hypothesized that CAV1 deficiency would impact drug-induced long-term plasticity in the nucleus accumbens (NAc). We first examined cell morphology of NAc medium spiny neurons in a striatal/cortical co-culture system before moving in vivo to study effects of CAV1 KO on cocaine-induced plasticity. Whole-cell patch-clamp recordings were performed to determine effects of chronic cocaine (15 mg/kg) on medium spiny neuron excitability. To test for deficits in behavioral plasticity, we examined the effect of CAV1 KO on locomotor sensitization. Results Disruption of CAV1 expression leads to baseline differences in medium spiny neuron (MSN) structural morphology, such that MSNs derived from CAV1 KO animals have increased dendritic arborization when cultured with cortical neurons. The effect was dependent on phospholipase C and cell-type intrinsic loss of CAV1. Slice recordings of nucleus accumbens shell MSNs revealed that CAV1 deficiency produces a loss of neuronal plasticity. Specifically, cocaine-induced firing rate depression was absent in CAV1 KO animals, whereas baseline electrophysiological properties were similar. This was reflected by a loss of cocaine-mediated behavioral sensitization in CAV1 KO animals, with unaffected baseline locomotor responsiveness. Conclusions This study highlights a critical role for nucleus accumbens CAV1 in plasticity related to the administration of drugs of abuse. Keywords Caveolin . Nucleus accumbens . Neuronal plasticity . Cocaine . Behavioral sensitization
Introduction Caveolins are small integral membrane proteins that spatially organize signaling proteins, including mGluRs, into functional microdomains (Patel et al. 2008; Francesconi et al. 2009; Takayasu et al. 2010). In peripheral tissue, caveolins form large oligomers—caveolae—that create invaginations in the
* Paul G. Mermelstein [email protected] 1
Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA
2
Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA
3
Present address: Department of Neurobiology, Duke University, Durham, NC 27710, USA
plasma membrane. Caveolae are not observed in the brain, but caveolin proteins are still expressed (Braun and Madison 2000; Boulware et al. 2007) and serve many of the same functions (Zheng et al. 2011). Specifi
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