Local regulation of striatal dopamine: A diversity of circuit mechanisms for a diversity of behavioral functions?

Current Opinion in Neurobiology, Journal Year: 2024, Volume and Issue: 85, P. 102839 - 102839

Published: Feb. 3, 2024

Language: Английский

---

Nigrostriatal dopamine modulates the striatal-amygdala pathway in auditory fear conditioning

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 9, 2023

Abstract The auditory striatum, a sensory portion of the dorsal plays an essential role in learning and memory. In contrast to its roles underlying mechanisms operant conditioning, however, little is known about contribution classical fear conditioning. Here, we reveal function striatum auditory-conditioned We find that optogenetically inhibiting striatal neurons impairs memory formation, which mediated through striatal-amygdala pathway. Using calcium imaging behaving mice, neuronal responses conditioned tones potentiate across acquisition expression. Furthermore, nigrostriatal dopaminergic projections important modulating conditioning-induced potentiation. Together, these findings demonstrate existence nigro-striatal-amygdala circuit for formation

Language: Английский

---

Dopamine Dysregulation in Reward and Autism Spectrum Disorder

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(7), P. 733 - 733

Published: July 22, 2024

Autism spectrum disorder (ASD) is primarily characterized by core deficits in social skills, communication, and cognition repetitive stereotyped behaviors. These manifestations are variable between individuals, ASD pathogenesis complex, with over a thousand implicated genes, many epigenetic factors, multiple environmental influences. The mesolimbic dopamine (DA) mediated brain reward system held to play key role, but the rapidly expanding literature reveals intricate, nuanced signaling involving wide array of loci, neurotransmitters receptor subtypes, neuronal variants. How altered DA may constitute downstream convergence manifold causal origins not well understood. A clear working framework help delineate common stages potential diagnostic interventional opportunities. Hence, we summarize known natural history context emerging data perspectives update signaling. Then, against this backdrop, proffer provisional that organizes into successive levels, including (1) genetic changes, (2) disrupted pathways, (3) dysregulated neurotransmitter/DA signaling, finally, (4) neurocognitive behavior possible antagonist/agonist based interventions. This subdivision logical progression potentially addressable parts facilitate rational formulation diagnostics targeted treatments.

Language: Английский

---

Shifting attention to orient or avoid: a unifying account of the tail of the striatum and its dopaminergic inputs

Current Opinion in Behavioral Sciences, Journal Year: 2024, Volume and Issue: 59, P. 101441 - 101441

Published: Sept. 2, 2024

The tail of the striatum (TS) is increasingly recognized as a unique subdivision striatum, characterized by its dense sensory inputs and projections received from distinct group dopamine neurons. Separate lines research have functional role TS, TS-projecting neurons, in three realms: saccadic eye movement towards valuable visual stimuli; tone-guided choice between two options; defensive responses to threatening stimuli. We propose framework for reconciling these diverse roles varied implementations conserved response salient stimuli, with TS providing teaching signal promote quick attentional shifts that facilitate stimulus-driven orientation and/or avoidance.

Language: Английский

---

Past, Present, and Future of Tools for Dopamine Detection

Neuroscience, Journal Year: 2023, Volume and Issue: 525, P. 13 - 25

Published: July 5, 2023

Language: Английский

---

Learning enhances representations of taste-guided decisions in the mouse gustatory insular cortex

Current Biology, Journal Year: 2024, Volume and Issue: 34(9), P. 1880 - 1892.e5

Published: April 16, 2024

Learning to discriminate overlapping gustatory stimuli that predict distinct outcomes—a feat known as discrimination learning—can mean the difference between ingesting a poison or nutritive meal. Despite obvious importance of this process, very little is about neural basis taste learning. In other sensory modalities, form learning can be mediated by either sharpening representations enhanced ability "decision-making" circuits interpret information. Given dual role insular cortex (GC) in encoding both and decision-related variables, region represents an ideal site for investigating how activity changes animals learn novel discrimination. Here, we present results from experiments relying on two-photon calcium imaging GC mice performing taste-guided mixture task. The task allows recording before after induced training increasingly similar pairs mixtures. Single-neuron population analyses show time-varying pattern activity, with early responses emerging delivery binary, choice-encoding later delay decision made. Our demonstrate that, while information encoded context task, improved performance are associated specific enhancement responses.

Language: Английский

---

A Drd1-cre mouse line with nucleus accumbens gene dysregulation exhibits blunted fentanyl seeking

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

Published: Feb. 19, 2025

Abstract The synthetic opioid fentanyl remains abundant in the illicit drug supply, contributing to tens of thousands overdose deaths every year. Despite this, neurobiological effects use remain largely understudied. nucleus accumbens (NAc) is a central locus promoting persistent and relapse, dependent on activity dopamine D1 receptors. NAc receptor-expressing medium spiny neurons (D1-MSNs) undergo molecular physiological adaptations that contribute negative affect during abstinence, but whether these neuroadaptations also promote relapse unclear. Here, we obtained Drd1-cre 120Mxu mice investigate D1-dependent mechanisms relapse. We serendipitously discovered this mouse line resistant seeking, despite similar intravenous self-administration, greater fentanyl-induced locomotion, compared wildtype counterparts. In naïve mice, found have elevated receptor expression NAc, alongside increased MSN marker genes Chrm4 Penk . show sensitivity agonist SKF-38393, exhibit divergent markers, receptors, glutamate subunits, TrkB after self-administration may underly blunted seeking. Finally, fentanyl-related behavior unaltered by chemogenetic manipulation D1-MSNs mice. Conversely, stimulation putative recapitulated seeking supporting role for aberrant D1-MSN signaling behavior. Together, our data uncover alterations gene function with implications susceptibility resistance developing disorder.

Language: Английский

---

Increased risk of chronic diseases and multimorbidity in middle-aged and elderly individuals with early vision, hearing, or dual sensory impairments: insights from prospective cohort studies and Mendelian randomization analysis

BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 25, 2025

Sensory impairments (SI), including vision (VI), hearing (HI), and dual sensory (DSI), are prevalent with aging, but their impact on disease risk remains unclear. This study investigates the epidemiological genetic associations between SIs 10 chronic categories multimorbidity. Using CHARLS study, participants were classified by self-reported VI/HI/DSI status in 2011 2013 into groups: "new onset, remission, persistent, no SI." Their incidence was tracked until 2018 sub-cohorts respectively. Mendelian randomization (MR) analyses used instruments from UK Biobank GWAS data 88,250/504,307 individuals for vision/hearing loss, outcome datasets consortia FinnGen, DIAMANTE, CKDGen, PGC, Catalog, International Parkinson's Disease Genomics Consortium. The cohort revealed that persistent HI significantly increased of heart (P < 0.001, HR 1.63, 95% CI 1.31–2.03), stroke 0.004, 1.59, 1.16–2.18), lung 0.002, 1.53, 1.17–1.99), emotional, nervous, or psychiatric problems 0.016, 2.03, 1.14–3.60). Persistent VI associated diabetes high blood sugar (DM/Hglu) 0.012, 1.11–2.38) 0.042, 1.02–2.31). MR confirmed these strong suggestive associations, indicating cardiovascular cerebrovascular events 61–170%, bronchitis 160%, schizophrenia 36%. In addition, raised hyperglycemia 2–4% function decline. Additionally, studies early DSI multiple diseases, while identified links hepatic failure, Parkinson's, Alzheimer's disease, hypertension, kidney renal failure. provides evidence perspectives demonstrates exposure to HI/VI/DSI increases developing diseases. These findings underscore need continuous monitoring timely intervention SI manage risks aging populations.

Language: Английский

---

WWC1 mutation drives dopamine dysregulation and synaptic imbalance in Tourette’s syndrome

Science Advances, Journal Year: 2025, Volume and Issue: 11(13)

Published: March 28, 2025

Tourette’s syndrome (TS) is a major neurodevelopmental disorder characterized by childhood-onset motor and vocal tics. A W88C mutation in WWC1 gene notable risk factor for TS, but the underlying molecular mechanisms remain unclear due to lack of suitable animal models. Here, we generate mutant mouse line with human (W88C Mut mice), which exhibits behavioral deficits similar those observed patients including repetitive behaviors sensorimotor gating abnormalities. The leads degradation kidney brain (KIBRA) protein via proteasomal pathway, evokes dopamine release dorsal striatum, disrupts synaptic function through dysregulation Hippo pathway. Neuron-specific overexpression wild-type rescues phenotypes mice. Together, this study not only provides valuable model studying TS also offers fresh insights into abnormalities TS.

Language: Английский

---

Dopamine prediction error signaling in a unique nigrostriatal circuit is critical for associative fear learning

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 29, 2025

Abstract Learning by experience that certain cues in the environment predict danger is crucial for survival. How dopamine (DA) circuits drive this form of associative learning not fully understood. Here, male mice, we demonstrate DA neurons projecting to a unique subregion dorsal striatum, posterior tail striatum (TS), encode prediction error (PE) signal during fear learning. These are necessary specifically acquisition learning, but once memory formed, and required forming cue-reward associations. Notably, temporally-precise inhibition or excitation terminals TS impairs enhances respectively. Furthermore, neuronal activity learning-induced patterns critically depend on input. Together, our results reveal PE signaling non-canonical nigrostriatal circuit important driving

Language: Английский

---