Dissociable encoding of motivated behavior by parallel thalamo-striatal projections DOI Open Access

Sofia Beas,

Isbah Khan,

Claire Gao

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 7, 2023

SUMMARY The successful pursuit of goals requires the coordinated execution and termination actions that lead to positive outcomes. This process is thought rely on motivational states are guided by internal drivers, such as hunger or fear. However, mechanisms which brain tracks shape instrumental not fully understood. paraventricular nucleus thalamus (PVT) a midline thalamic shapes motivated behaviors via its projections accumbens (NAc) 1–8 monitors state interoceptive inputs from hypothalamus brainstem 3,9–14 . Recent studies indicate PVT can be subdivided into two major neuronal subpopulations, namely D2(+) D2(–) , differ in genetic identity, functionality, anatomical connectivity other regions, including NAc 4,15,16 In this study, we used fiber photometry investigate vivo dynamics these distinct types mice performing reward foraging-like behavioral task. We discovered D2(−) neurons encode goal-oriented actions, respectively. Furthermore, activity population mirrored motivation parameters vigor satiety. Similarly, neurons, also some but much lesser extent. Importantly, features were largely preserved when was selectively assessed. Collectively, our results highlight existence parallel thalamo-striatal participate dynamic regulation goal pursuits provide insight actions.

Language: Английский

Distinct Behavioral Profiles and Neuronal Correlates of Heroin Vulnerability Versus Resiliency in a Multi-Symptomatic Model of Heroin Use Disorder in Rats DOI
Brittany N. Kuhn, Nazzareno Cannella, Ayteria D. Crow

et al.

American Journal of Psychiatry, Journal Year: 2025, Volume and Issue: 182(2), P. 198 - 208

Published: Jan. 15, 2025

The behavioral and diagnostic heterogeneity within the opioid use disorder (OUD) diagnosis is not readily captured in current animal models, limiting translational relevance of mechanistic research that conducted experimental animals. authors hypothesized a nonlinear clustering OUD-like traits would capture population yield subpopulations OUD vulnerable rats with distinct neurocircuit profiles. Over 900 male female heterogeneous stock rats, line capturing genetic present humans, were assessed for several measures heroin rewarded non-rewarded seeking behaviors. A stochastic block model analysis was used to assign vulnerable, intermediate, resilient clusters. Additional tests circuit analyses using c-fos protein activation on subpopulations. exhibited greater taking behaviors relative those intermediate Akin human diagnosis, further rat subclustering revealed different combinations traits, including sex differences. Lastly, cue-induced neuronal patterns differed between phenotypes. Behavioral differences recapitulated circuitry activation, preferential engagement extended amygdala stress males cortico-striatal drug cue-seeking females. Using approach reflective diagnosis. vulnerability resiliency associated patterns, posing this as tool assessing neurobiological mechanisms underpinning OUD.

Language: Английский

Citations

2
Dissociable encoding of motivated behavior by parallel thalamo-striatal projections DOI Creative Commons

Sofia Beas,

Isbah Khan,

Claire Gao

et al.

Current Biology, Journal Year: 2024, Volume and Issue: 34(7), P. 1549 - 1560.e3

Published: March 7, 2024

The successful pursuit of goals requires the coordinated execution and termination actions that lead to positive outcomes. This process relies on motivational states are guided by internal drivers, such as hunger or fear. However, mechanisms which brain tracks shape instrumental not fully understood. paraventricular nucleus thalamus (PVT) is a midline thalamic shapes motivated behaviors via its projections accumbens (NAc)

Language: Английский

Citations

9
Endocannabinoids facilitate transitory reward engagement through retrograde gain control DOI Open Access
David J. Marcus,

Anthony E. English,

Ge Chun

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Neuromodulatory signaling is poised to serve as a neural mechanism for gain control, acting crucial tuning factor influence neuronal activity by dynamically shaping excitatory and inhibitory fast neurotransmission. The endocannabinoid (eCB) system, the most widely expressed neuromodulatory system in mammalian brain, known filter inputs through retrograde, pre-synaptic action. However, whether eCBs exert retrograde control ultimately facilitate reward-seeking behaviors freely moving mammals not established. Using suite of vivo physiological, imaging, genetic machine learning-based approaches, we report fundamental role controlling behavioral engagement behavior defined thalamo-striatal circuit.

Language: Английский

Citations

1
The nucleus accumbens in reward and aversion processing: insights and implications DOI Creative Commons
Ying Xu, Yingjie Lin, Ming Yu

et al.

Frontiers in Behavioral Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Aug. 9, 2024

The nucleus accumbens (NAc), a central component of the brain's reward circuitry, has been implicated in wide range behaviors and emotional states. Emerging evidence, primarily drawing from recent rodent studies, suggests that function NAc aversion processing is multifaceted. Prolonged stress or drug use induces maladaptive neuronal which results pathological conditions. This review aims to provide comprehensive up-to-date insights on role motivated behavior regulation highlights areas demand further in-depth analysis. It synthesizes latest findings how distinct populations pathways contribute opposite valences. examines neuromodulators, especially monoamines, influence NAc's control over various motivational Furthermore, it delves into complex underlying mechanisms psychiatric disorders such as addiction depression evaluates prospective interventions restore functionality.

Language: Английский

Citations

8
Sex-specific behavioral and thalamo-accumbal circuit adaptations after oxycodone abstinence DOI Open Access
Yanaira Alonso‐Caraballo, Yan Li, Nicholas J. Constantino

et al.

Published: Jan. 13, 2025

Opioid use disorder is marked by a progressive change in the motivation to administer drug even presence of negative consequences. After long periods abstinence, urge return taking intensifies over time, known as incubation craving. Conditioned responses drug-related stimuli, can acquire motivational properties and exert control motivated behaviors leading relapse. Although, preclinical data suggest that behavioral expression opioid similar between male female rodents, we do not have conclusive results on sex differences craving relapse across abstinence periods. Here, investigated effects from oxycodone self-administration neurotransmission paraventricular thalamus (PVT) nucleus accumbens shell (NAcSh) pathway rats. Using optogenetics ex vivo electrophysiology, assessed synaptic strength glutamate release probability this pathway, well NAcSh medium spiny neurons (MSN) intrinsic excitability, slices rats which were subjected either 1 (acute) or 14 (prolonged) days forced after self-administration. Our revealed no somatic withdrawal symptoms following acute abstinence. However, found sex-specific enhancement cue-induced prolonged, but acute, self-administration, with females exhibiting higher rates. Notably, prolonged led increases at PVT-NAcSh inputs compared saline controls both sexes, was observed Thus, time-dependent increase These findings leads significant changes, contributing heightened vulnerability, highlighting need for targeted therapeutic strategies disorder.

Language: Английский

Citations

0
Sex-specific behavioral and thalamo-accumbal circuit adaptations after oxycodone abstinence DOI Open Access
Yanaira Alonso‐Caraballo, Yan Li, Nicholas J. Constantino

et al.

Published: Jan. 13, 2025

Opioid use disorder is marked by a progressive change in the motivation to administer drug even presence of negative consequences. After long periods abstinence, urge return taking intensifies over time, known as incubation craving. Conditioned responses drug-related stimuli, can acquire motivational properties and exert control motivated behaviors leading relapse. Although, preclinical data suggest that behavioral expression opioid similar between male female rodents, we do not have conclusive results on sex differences craving relapse across abstinence periods. Here, investigated effects from oxycodone self-administration neurotransmission paraventricular thalamus (PVT) nucleus accumbens shell (NAcSh) pathway rats. Using optogenetics ex vivo electrophysiology, assessed synaptic strength glutamate release probability this pathway, well NAcSh medium spiny neurons (MSN) intrinsic excitability, slices rats which were subjected either 1 (acute) or 14 (prolonged) days forced after self-administration. Our revealed no somatic withdrawal symptoms following acute abstinence. However, found sex-specific enhancement cue-induced prolonged, but acute, self-administration, with females exhibiting higher rates. Notably, prolonged led increases at PVT-NAcSh inputs compared saline controls both sexes, was observed Thus, time-dependent increase These findings leads significant changes, contributing heightened vulnerability, highlighting need for targeted therapeutic strategies disorder.

Language: Английский

Citations

0
Electrophysiological analysis of paraventricular thalamic neurons co-expressing kappa and mu opioid receptors DOI Creative Commons
Eloise J. Kuijer, Sarah Bailey,

D.J. Heal

et al.

Neuropharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 110407 - 110407

Published: March 1, 2025

Language: Английский

Citations

0
The encoding of interoceptive-based predictions by the paraventricular nucleus of the thalamus D2+ neurons DOI Open Access

Briana Machen,

S. Miller, Alison W. Xin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Understanding how the brain integrates internal physiological states with external sensory cues to guide behavior is a fundamental question in neuroscience. This process relies on interoceptive predictions-internal models that anticipate changes body's state based inputs and prior experiences. Despite recent advances identifying neural substrates of predictions, precise neuronal circuits involved remain elusive. In our study, we demonstrate Dopamine 2 Receptor (D2+) expressing neurons paraventricular nucleus thalamus (PVT) play key roles interoception predictions. Specifically, these are engaged behaviors leading physiologically relevant outcomes, their activity highly dependent mice expected outcome. Furthermore, show chronic inhibition PVT D2+ impairs long-term performance interoceptive-guided motivated behavior. Collectively, findings provide insights into role learning updating state-dependent by integrating past experiences current conditions optimize goal-directed

Language: Английский

Citations

0
Prefrontal cortex excitatory neurons show distinct response to heroin-associated cue and social stimulus after prolonged heroin abstinence in mice DOI

Yunwanbin Wang,

Junting Liu,

Shuwen Yue

et al.

Neuropsychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 13, 2025

Language: Английский

Citations

0
A multi-symptomatic model of heroin use disorder in rats reveals distinct behavioral profiles and neuronal correlates of heroin vulnerability versus resiliency DOI Open Access
Brittany N. Kuhn, Nazzareno Cannella, Ayteria D. Crow

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 23, 2024

The behavioral and diagnostic heterogeneity within human opioid use disorder (OUD) diagnosis is not readily captured in current animal models, limiting translational relevance of the mechanistic research that conducted experimental animals. We hypothesize a non-linear clustering OUD-like traits will capture population yield subpopulations OUD vulnerable rats with distinct neurocircuit profiles.

Language: Английский

Citations

2