Dysregulation of kappa opioid receptor neuromodulation of lateral habenula synaptic function following a repetitive mild traumatic brain injury DOI
William J. Flerlage, Sarah C. Simmons,

Emily Thomas

et al.

Pharmacology Biochemistry and Behavior, Journal Year: 2024, Volume and Issue: 243, P. 173838 - 173838

Published: July 26, 2024

Language: Английский

Neocortical somatostatin neuron diversity in cognition and learning DOI Creative Commons
Eunsol Park, Matthew B. Mosso, Alison L. Barth

et al.

Trends in Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2

Neurotransmitters crosstalk and regulation in the reward circuit of subjects with behavioral addiction DOI Creative Commons
Zhenlei Peng, Qiyu Jia,

Junxiong Mao

et al.

Frontiers in Psychiatry, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

Behavioral addictive disorders (BADs) have become a significant societal challenge over time. The central feature of BADs is the loss control engaging in and continuing behaviors, even when facing negative consequences. neurobiological underpinnings primarily involve impairments reward circuitry, encompassing ventral tegmental area, nucleus accumbens striatum, prefrontal cortex. These brain regions form networks that communicate through neurotransmitter signaling, leading to changes individuals with behavioral addictions. While dopamine has long been associated process, recent research highlights role other key neurotransmitters like serotonin, glutamate, endorphins BADs' development. interact within creating potential targets for therapeutic intervention. This improved understanding systems provides foundation developing targeted treatments helps clinicians select personalized approaches.

Language: Английский

Citations

1

The Impact of Optical Undersampling on the Ca2+ Signal Resolution in Ca2+ Imaging of Spontaneous Neuronal Activity DOI Creative Commons
Katarina Miličević, Violetta O. Ivanova,

Thomas J. Brazil

et al.

Journal of Integrative Neuroscience, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 21, 2025

Background: In neuroscience, Ca2+ imaging is a prevalent technique used to infer neuronal electrical activity, often relying on optical signals recorded at low sampling rates (3 30 Hz) across multiple neurons simultaneously. This study investigated whether increasing the rate preserves critical information that may be missed slower acquisition speeds. Methods: Primary cultures were prepared from cortex of newborn pups. Neurons loaded with Oregon Green BAPTA-1 AM (OGB1-AM) fluorescent indicator. Spontaneous activity was (14 and high (500 rates, same (n = 269) analyzed under both conditions. We compared signal amplitude, duration, frequency. Results: Although recurring transients appeared visually similar 14 Hz 500 Hz, quantitative analysis revealed significantly faster rise times shorter durations (half-widths) higher rate. Small-amplitude transients, undetectable became evident particularly in neuropil (putative dendrites axons), but not nearby cell bodies. Large exhibited greater amplitudes temporal dynamics somas, potentially due surface-to-volume ratio dendrites. bulk-loaded OGB1-AM, nucleus-mediated distortions observed every neuron examined 57). Specifically, two regions interest (ROIs) different segments body displayed dye accumulation nucleus. Conclusions: Our findings reveal undersampling leads three types loss: (1) distortion for large-amplitude (2) failure detect small-amplitude bodies, (3) omission neuropil.

Language: Английский

Citations

0

The Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction DOI Creative Commons
Renata C.N. Marchette,

Leandro F. Vendruscolo,

George F. Koob

et al.

Current Addiction Reports, Journal Year: 2025, Volume and Issue: 12(1)

Published: Feb. 4, 2025

Abstract Purpose of Review Drug addiction is characterized by compulsive drug seeking and use, accompanied negative emotional states (hyperkatifeia) heightened pain sensitivity (hyperalgesia) during withdrawal. Both hyperalgesia hyperkatifeia are integral components substance use disorders, negatively impacting treatment recovery. The underlying neurobiological mechanisms involve alterations brain reward stress circuits, including the dynorphin/κ-opioid receptor (KOR) system. dynorphin/KOR system modulates perception, affect, addictive behaviors. Here, we review preclinical evidence signaling in opioid withdrawal-induced hyperkatifeia. Recent Findings In dependence models, pharmacological genetic interventions attenuate somatic motivational signs withdrawal addictive-like behaviors, highlighting its therapeutic potential. Understanding intricate interplay between signaling, hyperalgesia, hyperkatifeia, offers novel insights into strategies for disorder other disorders. Summary Further research needed to elucidate precise sexual dimorphism identify targeted mitigate facilitate recovery from addiction.

Language: Английский

Citations

0

An integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology DOI
Sean C. Piantadosi, Min‐Kyu Lee, Mingzheng Wu

et al.

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

Published: April 1, 2025

Language: Английский

Citations

0

Endogenous opioid dynamics in the dorsal striatum sculpt neural activity to control goal-directed action DOI Creative Commons
Raajaram Gowrishankar, Madelyn M. Hjort,

Abigail J. Elerding

et al.

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

Published: May 20, 2024

Abstract Endogenous neuropeptides are uniquely poised to regulate neuronal activity and behavior across multiple timescales. Traditional studies ascribing neuropeptide contributions lack spatiotemporal precision. The endogenous opioid dynorphin is highly enriched in the dorsal striatum, known be critical for regulating goal-directed behavior. However, locus, precise timescale, or functional role of dyn-KOR signaling on unknown. Here, we report that local, time-locked release from dorsomedial striatum necessary sufficient using a suite high resolution modern approaches including vivo two-photon imaging, biosensor detection, conditional deletions optogenetic manipulations. We discovered glutamatergic axon terminals basolateral amygdala evoke striatal release, resulting retrograde presynaptic GPCR inhibition during Collectively, our findings isolate causal at rapid timescales, subsequent tuning promoting fundamental behaviors.

Language: Английский

Citations

3

Social Isolation Induces Changes in the Monoaminergic Signalling in the Rat Medial Prefrontal Cortex DOI Creative Commons
Vivien Csikós, Fanni Dóra,

Tamás Láng

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(12), P. 1043 - 1043

Published: June 17, 2024

(1) Background: The effects of short-term social isolation during adulthood have not yet been fully established in rats behaviourally, and at all transcriptomically the medial prefrontal cortex (mPFC). (2) Methods: We measured behavioural housing adult male pairs or alone for 10 days. also used RNA sequencing to measure accompanying gene expression alterations mPFC rats. (3) Results: isolated animals exhibited reduced sociability novelty preference, but increased interaction. There was no change their aggression, anxiety, depression-like activity. Transcriptomic analysis revealed a differential 46 genes between groups. KEGG pathway showed that differentially expressed are involved neuroactive ligand-receptor interactions, particularly dopaminergic peptidergic systems, addiction. Subsequent validation confirmed decreased level three altered genes: regulator G protein signalling 9 (Rgs9), serotonin receptor 2c (Htr2c), Prodynorphin (Pdyn), which dopaminergic, serotonergic, function, respectively. Antagonizing Htr2c its role discrimination. (4) Conclusions: Social homeostatic regulations include monoaminergic systems mPFC.

Language: Английский

Citations

3

Dysregulation of Kappa Opioid Receptor Neuromodulation of Lateral Habenula Synaptic Function following a Repetitive Mild Traumatic Brain Injury DOI Open Access
William J. Flerlage, Sarah C. Simmons,

Emily Thomas

et al.

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

Published: May 1, 2024

Abstract Mild traumatic brain injury (mTBI) increases the risk of cognitive deficits, affective disorders, anxiety and substance use disorder in affected individuals. Substantial evidence suggests a critical role for lateral habenula (LHb) pathophysiology psychiatric disorders. Recently, we demonstrated causal link between persistent mTBI-induced LHb hyperactivity due to synaptic excitation/inhibition (E/I) imbalance motivational deficits self-care grooming behavior young adult male mice using repetitive closed head mTBI model. One major neuromodulatory systems that is responsive spinal cord injuries, influences states also modulates activity dynorphin/kappa opioid receptor (Dyn/KOR) system. However, effects on KOR neuromodulation function unknown. To address this, first used retrograde tracing anatomically verify mouse indeed receives Dyn/KOR expressing projections. We identified several KOR-expressing Dyn-expressing inputs projecting LHb. then functionally evaluated vitro modulation spontaneous within female sham at 4week post-injury Similar what previously reported mice, presynaptically diminished onto neurons, while shifting E/I toward excitation Furthermore, activation either male/female generally suppressed glutamatergic transmission without altering GABAergic transmission, resulting significant reduction ratios decreased excitatory drive neurons mice. Interestingly following mTBI, responses synapses were observed comparable those sham, acquired an additional sensitivity KOR-mediated inhibition. Thus, contrast LHb, GABA release probability response stimulation chronic loss net inhibition Overall, our findings uncovered unknown sources Dyn/KOR-expressing Further, demonstrate engagement intra-LHb signaling provides global suppression which could act as inhibitory braking mechanism prevent hyperexcitability. The modulatory action by contribute after with serving disinhibitory

Language: Английский

Citations

0

An integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology DOI Open Access
Sean C. Piantadosi, Min‐Kyu Lee, Mingzheng Wu

et al.

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

Published: May 14, 2024

Neurotechnologies and genetic tools for dissecting neural circuit functions have advanced rapidly over the past decade, although development of complementary pharmacological method-ologies has comparatively lagged. Understanding precise mechanisms neuroactive compounds is critical advancing basic neurobiology neuropharmacology, as well developing more effective treatments neurological neuropsychiatric disorders. However, integrating modern assessing activity in large-scale networks with spatially localized drug delivery remains a major challenge. Here, we present dual microfluidic-photometry platform that enables simultaneous intracranial dynamics monitoring rodent brain. The integrated combines wireless, battery-free, miniaturized fluidic microsystem optical probes, allowing temporally specific while recording activity-dependent fluorescence using genetically encoded calcium indicators (GECIs), neurotransmitter sensors GRAB

Language: Английский

Citations

0

Endogenous Opioid Dynamics in the Dorsal Striatum Sculpt Neural Activity to Control Goal-Directed Action DOI
Raajaram Gowrishankar,

Madelyn M. Gray,

Abigail J. Elerding

et al.

Published: Jan. 1, 2024

Endogenous neuropeptides are uniquely poised to regulate neuronal activity and behavior across multiple timescales. Traditional studies ascribing neuropeptide contributions lack spatiotemporal precision. The endogenous opioid dynorphin is highly enriched in the dorsal striatum, known be critical for regulating goal-directed behavior. However, locus, precise timescale, or functional role of dyn-KOR signaling on unknown. Here, we report that local, time-locked release from dorsomedial striatum necessary sufficient using a suite high resolution modern approaches including vivo two-photon imaging, biosensor detection, conditional deletions optogenetic manipulations. We discovered glutamatergic axon terminals basolateral amygdala evoke striatal release, resulting retrograde presynaptic GPCR inhibition during Collectively, our findings isolate causal at rapid timescales, subsequent tuning promoting fundamental behaviors.

Language: Английский

Citations

0