Basal forebrain-lateral habenula inputs and control of impulsive behavior.

Autor: Hwang EK; Computational and Systems Neuroscience Branch, Electrophysiology Research Section, U.S. Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.; Department of Behavioral Neuroscience, Oregon Health Sciences University, Portland, OR, 97239, USA., Zapata A; Computational and Systems Neuroscience Branch, Electrophysiology Research Section, U.S. Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA., Hu V; Computational and Systems Neuroscience Branch, Electrophysiology Research Section, U.S. Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA., Hoffman AF; Computational and Systems Neuroscience Branch, Electrophysiology Research Section, U.S. Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA., Wang HL; Integrative Neuroscience Research Branch, Neuronal Networks Section, U.S. Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA., Liu B; Integrative Neuroscience Research Branch, Neuronal Networks Section, U.S. Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA., Morales M; Integrative Neuroscience Research Branch, Neuronal Networks Section, U.S. Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA., Lupica CR; Computational and Systems Neuroscience Branch, Electrophysiology Research Section, U.S. Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA. clupica@mail.nih.gov.
Jazyk: angličtina
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2024 Dec; Vol. 49 (13), pp. 2060-2068. Date of Electronic Publication: 2024 Aug 18.
DOI: 10.1038/s41386-024-01963-7
Abstrakt: Deficits in impulse control are observed in several neurocognitive disorders, including attention deficit hyperactivity (ADHD), substance use disorders (SUDs), and those following traumatic brain injury (TBI). Understanding brain circuits and mechanisms contributing to impulsive behavior may aid in identifying therapeutic interventions. We previously reported that intact lateral habenula (LHb) function is necessary to limit impulsivity defined by impaired response inhibition in rats. Here, we examine the involvement of a synaptic input to the LHb on response inhibition using cellular, circuit, and behavioral approaches. Retrograde fluorogold tracing identified basal forebrain (BF) inputs to LHb, primarily arising from ventral pallidum and nucleus accumbens shell (VP/NAcs). Glutamic acid decarboxylase and cannabinoid CB1 receptor (CB1R) mRNAs colocalized with fluorogold, suggesting a cannabinoid modulated GABAergic pathway. Optogenetic activation of these axons strongly inhibited LHb neuron action potentials and GABA release was tonically suppressed by an endogenous cannabinoid in vitro. Behavioral experiments showed that response inhibition during signaled reward omission was impaired when VP/NAcs inputs to LHb were optogenetically stimulated, whereas inhibition of this pathway did not alter LHb control of impulsivity. Systemic injection with the psychotropic phytocannabinoid, Δ 9 -tetrahydrocannabinol (Δ 9 -THC), also increased impulsivity in male, and not female rats, and this was blocked by LHb CB1R antagonism. However, as optogenetic VP/NAcs pathway inhibition did not alter impulse control, we conclude that the pro-impulsive effects of Δ 9 -THC likely do not occur via inhibition of this afferent. These results identify an inhibitory LHb afferent that is controlled by CB1Rs that can regulate impulsive behavior.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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