title: ΔFosB induction in striatal medium spiny neuron subtypes in response to chronic pharmacological, emotional, and optogenetic stimuli.
abstract: The transcription factor, ΔFosB, is robustly and persistently induced in striatum by several chronic stimuli, such as drugs of abuse, antipsychotic drugs, natural rewards, and stress. However, very few studies have examined the degree of ΔFosB induction in the two striatal medium spiny neuron (MSN) subtypes. We make use of fluorescent reporter BAC transgenic mice to evaluate induction of ΔFosB in dopamine receptor 1 (D1) enriched and dopamine receptor 2 (D2) enriched MSNs in ventral striatum, nucleus accumbens (NAc) shell and core, and in dorsal striatum (dStr) after chronic exposure to several drugs of abuse including cocaine, ethanol, Δ(9)-tetrahydrocannabinol, and opiates; the antipsychotic drug, haloperidol; juvenile enrichment; sucrose drinking; calorie restriction; the serotonin selective reuptake inhibitor antidepressant, fluoxetine; and social defeat stress. Our findings demonstrate that chronic exposure to many stimuli induces ΔFosB in an MSN-subtype selective pattern across all three striatal regions. To explore the circuit-mediated induction of ΔFosB in striatum, we use optogenetics to enhance activity in limbic brain regions that send synaptic inputs to NAc; these regions include the ventral tegmental area and several glutamatergic afferent regions: medial prefrontal cortex, amygdala, and ventral hippocampus. These optogenetic conditions lead to highly distinct patterns of ΔFosB induction in MSN subtypes in NAc core and shell. Together, these findings establish selective patterns of ΔFosB induction in striatal MSN subtypes in response to chronic stimuli and provide novel insight into the circuit-level mechanisms of ΔFosB induction in striatum.
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, Departments of Psychiatry and of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York 10029, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, Department of Pharmacology and Toxicology and the Research Institute on Addictions, State University of New York at Buffalo, New York, New York 14214, and Institut National de la Santé et de la Recherche Médicale, U952, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7224, UPMC, Paris, 75005, France.
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Lobo
authors.forename: Samir
authors.initials: S
authors.lastname: Zaman
authors.forename: Diane M
authors.initials: DM
authors.lastname: Damez-Werno
authors.forename: Ja Wook
authors.initials: JW
authors.lastname: Koo
authors.forename: Rosemary C
authors.initials: RC
authors.lastname: Bagot
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: DiNieri
authors.forename: Alexandria
authors.initials: A
authors.lastname: Nugent
authors.forename: Eric
authors.initials: E
authors.lastname: Finkel
authors.forename: Dipesh
authors.initials: D
authors.lastname: Chaudhury
authors.forename: Ramesh
authors.initials: R
authors.lastname: Chandra
authors.forename: Efrain
authors.initials: E
authors.lastname: Riberio
authors.forename: Jacqui
authors.initials: J
authors.lastname: Rabkin
authors.forename: Ezekiell
authors.initials: E
authors.lastname: Mouzon
authors.forename: Roger
authors.initials: R
authors.lastname: Cachope
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cheer
authors.forename: Ming-Hu
authors.initials: MH
authors.lastname: Han
authors.forename: David M
authors.initials: DM
authors.lastname: Dietz
authors.forename: David W
authors.initials: DW
authors.lastname: Self
authors.forename: Yasmin L
authors.initials: YL
authors.lastname: Hurd
authors.forename: Vincent
authors.initials: V
authors.lastname: Vialou
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology*; D015259:Dopamine Agents / Q000494:pharmacology*; D013759:Dronabinol / Q000494:pharmacology; D004644:Emotions / Q000187:drug effects*; D004777:Environment; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000145:classification / Q000187:drug effects; D062308:Optogenetics; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics
chemical_list: D000928:Antidepressive Agents; D063386:Cannabinoid Receptor Agonists; D015259:Dopamine Agents; C483819:Fosb protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D049452:Green Fluorescent Proteins; D013759:Dronabinol; D010751:Phosphopyruvate Hydratase