Department of Psychiatry; Graduate School of Biomedical Sciences, Neuroscience Program; Gene Therapy Center; Martin Lab; Tapper Lab
Molecular and Cellular Neuroscience | Psychiatry | Psychiatry and Psychology
Voltage-gated sodium channels are essential for generating the initial rapid depolarization of neuronal membrane potential during action potentials (APs) that enable cell-to-cell communication, the propagation of signals throughout the brain, and the induction of synaptic plasticity. Although all brain neurons express one or several variants coding for the core pore-forming sodium channel alpha subunit, the expression of the beta (beta1-4) auxiliary subunits varies greatly. Of particular interest is the beta4 subunit, encoded by the Scn4b gene, that is highly expressed in dorsal and ventral (i.e., nucleus accumbens - NAc) striata compared to other brain regions, and that endows sodium channels with unique gating properties. However, its role on neuronal activity, synaptic plasticity, and behaviors related to drugs of abuse remains poorly understood. Combining whole-cell patch-clamp recordings with two-photon calcium imaging in Scn4b knockout (KO) and knockdown mice, we found that Scn4b altered the properties of APs in core accumbens medium spiny neurons (MSNs). These alterations are associated with a reduction of the probability of MSNs to evoke spike-timing-dependent long-term depression (tLTD) and a reduced ability of backpropagating APs to evoke dendritic calcium transients. In contrast, long-term potentiation (tLTP) remained unaffected. Interestingly, we also showed that amphetamine-induced locomotor activity was significantly reduced in male Scn4b KO mice compared to wild-type controls. Taken together, these data indicate that the Scn4b subunit selectively controls tLTD by modulating dendritic calcium transients evoked by backpropagating APs.
nucleus accumbens, spike-timing-dependent plasticity, sodium channel, Scn4b, knockout mice, calcium imaging, dendrites, long-term depression
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Copyright © 2017 Ji, Saha, Gao, Lasek, Homanics, Guildford, Tapper and Martin.
DOI of Published Version
Front Cell Neurosci. 2017 Feb 13;11:17. doi: 10.3389/fncel.2017.00017. eCollection 2017. eCollection 2017. Link to article on publisher's site
Frontiers in cellular neuroscience
Ji X, Saha S, Gao G, Lasek AW, Homanics GE, Derner MG, Tapper AR, Martin GE. (2017). The Sodium Channel beta4 Auxiliary Subunit Selectively Controls Long-Term Depression in Core Nucleus Accumbens Medium Spiny Neurons. Psychiatry Publications and Presentations. https://doi.org/10.3389/fncel.2017.00017. Retrieved from https://escholarship.umassmed.edu/psych_pp/756
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