title: The Sodium Channel β4 Auxiliary Subunit Selectively Controls Long-Term Depression in Core Nucleus Accumbens Medium Spiny Neurons.
abstract: 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 α subunit, the expression of the β (β1-4) auxiliary subunits varies greatly. Of particular interest is the β4 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.
authors.affiliation: Department of Psychiatry, The Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester MA, USA.
authors.forename: Xincai
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Psychiatry, The Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester MA, USA.
authors.forename: Sucharita
authors.initials: S
authors.lastname: Saha
authors.affiliation: Gene Therapy Center, University of Massachusetts Medical School, Worcester MA, USA.
authors.forename: Guangping
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago IL, USA.
authors.forename: Amy W
authors.initials: AW
authors.lastname: Lasek
authors.affiliation: Department of Anesthesiology, University of Pittsburgh, Pittsburgh PA, USA.
authors.forename: Gregg E
authors.initials: GE
authors.lastname: Homanics
authors.affiliation: Department of Psychiatry, The Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester MA, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Guildford
authors.affiliation: Department of Psychiatry, The Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester MA, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Tapper
authors.affiliation: Department of Psychiatry, The Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester MA, USA.
authors.forename: Gilles E
authors.initials: GE
authors.lastname: Martin
keywords: Scn4b; calcium imaging; dendrites; knockout mice; long-term depression; nucleus accumbens; sodium channel; spike-timing-dependent plasticity