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

Agustin Zapata (Left) and Eun-Kyung Hwang (Right)

Hot Off the Press – August 27, 2024

Published in Neuropsychopharmacology by Eun-Kyung Hwang, Agustin Zapata and Carl Lupica, et al. from the NIDA IRP Electrophysiology Research Section.

Summary

Impulsive behavior is both a predictor and a consequence of drug use and substance use disorders, as well as a symptom of other neuropsychiatric illnesses such as traumatic brain injury, obsessive compulsive disorder, ADHD and bipolar disorder. Our prior work implicated a brain area known as the lateral habenula (LHb) in the control of impulsive behaviors in rats. In the present study we characterize an inhibitory input to the LHb that arises from neurons in the basal forebrain, or more specifically, in the ventral pallidum and nucleus accumbens shell (VP/NAcs), using neuroanatomical and electrophysiological methods. We also find that this LHb input is controlled by the endogenous cannabinoid system, and in behavioral experiments we show that activation of this input increases impulsive behavior in rats. As the VP/NAcs has been implicated in reward-based behaviors, our study suggests that it may also regulate impulsive behavior related to reward seeking via control of LHb activity.

Publication Information

Hwang, Eun-Kyung; Zapata, Agustin; Hu, Vivian; Hoffman, Alexander F; Wang, Hui-Ling; Liu, Bing; Morales, Marisela; Lupica, Carl R

Basal forebrain-lateral habenula inputs and control of impulsive behavior Journal Article

In: Neuropsychopharmacology, 2024, ISSN: 1740-634X.

Abstract | Links

@article{pmid39155312,

title = {Basal forebrain-lateral habenula inputs and control of impulsive behavior},

author = {Eun-Kyung Hwang and Agustin Zapata and Vivian Hu and Alexander F Hoffman and Hui-Ling Wang and Bing Liu and Marisela Morales and Carl R Lupica},

url = {https://pubmed.ncbi.nlm.nih.gov/39155312/},

doi = {10.1038/s41386-024-01963-7},

issn = {1740-634X},

year  = {2024},

date = {2024-08-01},

urldate = {2024-08-01},

journal = {Neuropsychopharmacology},

abstract = {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-tetrahydrocannabinol (Δ-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-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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}