Dataset Information

Hypothalamic control of male aggression-seeking behavior.

ABSTRACT: In many vertebrate species, certain individuals will seek out opportunities for aggression, even in the absence of threat-provoking cues. Although several brain areas have been implicated in the generation of attack in response to social threat, little is known about the neural mechanisms that promote self-initiated or 'voluntary' aggression-seeking when no threat is present. To explore this directly, we utilized an aggression-seeking task in which male mice self-initiated aggression trials to gain brief and repeated access to a weaker male that they could attack. In males that exhibited rapid task learning, we found that the ventrolateral part of the ventromedial hypothalamus (VMHvl), an area with a known role in attack, was essential for aggression-seeking. Using both single-unit electrophysiology and population optical recording, we found that VMHvl neurons became active during aggression-seeking and that their activity tracked changes in task learning and extinction. Inactivation of the VMHvl reduced aggression-seeking behavior, whereas optogenetic stimulation of the VMHvl accelerated moment-to-moment aggression-seeking and intensified future attack. These data demonstrate that the VMHvl can mediate both acute attack and flexible seeking actions that precede attack.

SUBMITTER: Falkner AL

PROVIDER: S-EPMC4853470 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Publications

Hypothalamic control of male aggression-seeking behavior.

Falkner Annegret L AL Grosenick Logan L Davidson Thomas J TJ Deisseroth Karl K Lin Dayu D

Nature neuroscience 20160307 4

In many vertebrate species, certain individuals will seek out opportunities for aggression, even in the absence of threat-provoking cues. Although several brain areas have been implicated in the generation of attack in response to social threat, little is known about the neural mechanisms that promote self-initiated or 'voluntary' aggression-seeking when no threat is present. To explore this directly, we utilized an aggression-seeking task in which male mice self-initiated aggression trials to g ...[more]

PMID: 26950005

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Project description:Recovery from opioid use disorder (OUD) and maintenance of abstinence from opioid use is hampered by perseverant drug cravings that may persist for months after cessation of drug use. Drug cravings can intensify during the abstinence period, a phenomenon referred to as the 'incubation of craving' that has been well-described in preclinical studies. We previously reported that animals that self-administered heroin at a dosage of 0.075 mg/kg/infusion (HH) paired with discrete drug cues displayed robust incubation of heroin craving behavior after 21 days (D) of forced abstinence, an effect that was not observed with a lower dosage (0.03 mg/kg/infusion; HL). Here, we sought to elucidate molecular mechanisms underlying long-term heroin seeking behavior by profiling microRNA (miRNA) pathways in the orbitofrontal cortex (OFC), a brain region that modulates incubation of heroin seeking. miRNAs are small noncoding RNAs with long half-lives that have emerged as critical regulators of drug seeking behavior but their expression in the OFC has not been examined in any drug exposure paradigm. We employed next generation sequencing to detect OFC miRNAs differentially expressed after 21D of forced abstinence between HH and HL animals, and proteomics analysis to elucidate miRNA-dependent translational neuroadaptations. We identified 55 OFC miRNAs associated with incubation of heroin craving, including miR-485-5p, which was significantly downregulated following 21D forced abstinence in HH but not HL animals. We bidirectionally manipulated miR-485-5p in the OFC to demonstrate that miR-485-5p can regulate long-lasting heroin seeking behavior after extended forced abstinence. Proteomics analysis identified 45 proteins selectively regulated in the OFC of HH but not HL animals that underwent 21D forced abstinence, of which 7 were putative miR-485-5p target genes. Thus, the miR-485-5p pathway is dysregulated in animals with a phenotype of persistent heroin craving behavior and OFC miR-485-5p pathways may function to support long-lasting heroin seeking.

Dataset Information

Hypothalamic control of male aggression-seeking behavior.

Publications

Hypothalamic control of male aggression-seeking behavior.

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