PXD055005

PXD055005 is an original dataset announced via ProteomeXchange.

Title	Epigenetic control of an auxiliary subunit of sodium voltage-gated channels regulates the strength of drug-cue associations and relapse-like cocaine seekingEpigenetic control of an auxiliary subunit of sodium voltage-gated channels regulates the strength of drug-cue associations and relapse-like cocaine seeking
Description	Repeated use of illicit drugs produces long-lasting and prepotent drug-cue associations that increase vulnerability for relapse in individuals with a substance use disorder. Epigenetic factors like histone deacetylase 5 (HDAC5) play a key role in regulating the formation of drug-cue associations, but the underlying mechanisms remain unclear. We show here that two conserved cysteines located near HDAC5’s catalytic domain are required for its intrinsic deacetylase activity, and that HDAC5’s deacetylase activity is required in nucleus accumbens (NAc) medium spiny neurons (MSNs) to limit their intrinsic excitability and relapse-like cue-reinstated cocaine seeking. Moreover, we show that HDAC5 limits NAc MSN firing rate and cue-reinstated cocaine seeking by deacetylase-dependent repression of Scn4b, a novel HDAC5 target gene that encodes an auxiliary subunit of voltage-gated ion channels. Taken together, our data suggest that epigenetic control of NAc Scn4b governs the plasticity underlying formation of drug-cue associations through modulation of NAc MSN intrinsic excitability.
HostingRepository	PRIDE
AnnounceDate	2025-02-18
AnnouncementXML	Submission_2025-02-18_10:57:12.235.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Bethard
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	dehydroalanine (Cys); L-cysteine sulfenic acid; cysteinylation (disulfide with free L-cysteine); N-ethylmaleimide derivatized cysteine; reduction of disulfide crosslink in cystine to two cysteines; L-cysteine sulfinic acid; monohydroxylated residue; L-cysteic acid (L-cysteine sulfonic acid); iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-19 12:17:23	ID requested
⏵ 1	2025-02-18 10:57:12	announced

10.1016/J.BIOPSYCH.2025.01.027;

submitter keyword: reinstatement behavior, excitability, nucleus accumbens, substance use disorder,epigenetics

Christopher W. Cowan
contact affiliation	Medical University of South Carolina, Department of Neuroscience, Charleston, SC, USA
contact email	cowanc@musc.edu
lab head
Jennifer Bethard
contact affiliation	Medical University of SC
contact email	bethard@musc.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/02/PXD055005

PRIDE project URI

• PRIDE
  1. PXD055005
     1. Label: PRIDE project
     2. Name: Epigenetic control of an auxiliary subunit of sodium voltage-gated channels regulates the strength of drug-cue associations and relapse-like cocaine seekingEpigenetic control of an auxiliary subunit of sodium voltage-gated channels regulates the strength of drug-cue associations and relapse-like cocaine seeking