Dynamics of burst synchronization induced by excitatory inputs on midbrain dopamine neurons DOI Creative Commons
M X Chen

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

Published: Dec. 28, 2023

Abstract Dopamine (DA) signals play critical roles in reward-related behavior, decision making, and learning. Yet the mainstream notion that DA are encoded by temporal dynamics of individual cell activity is increasingly contested with data supporting prefer to be spatial organization neuron populations. However, how distributed parallel excitatory afferent inputs simultaneously induce burst synchronization (BS) unclear. Our previous work implies could presumably transition from an integrator a resonator if increase further. Here responses networked neurons different intensity investigated. It found as NMDA conductance increases, network will resting state asynchronization (BA) then BS state, showing bounded BA region space. Furthermore, it muscarinic receptors modulated Ca 2+ dependent cationic (CAN) both boundaries between BA, gradually decrease. Phase plane analysis on reduced model unveils underpins changes dynamics. Slow-fast dissection full uncovers underlying mechanism synergy inducing emerge enlargement nonlinear positive feedback relationship more influx provided additional current I CAN added receptors. Moreover, lag volume transmission has no effect inputs-elicited except for requiring inputs. These findings shed new lights understanding collective behavior cells population regulated inputs, might provide perspective abnormal release pathological states. Author summary The importance beyond doubt, so their encoding very important biological significance draws widespread attention. uniform, broadly signal homogeneity across dopamine diversity target regions. article proposes diverse can not only regulate activity, but also synergistically populations changing local cells, namely integrators resonators. According our perspective, many difficult interpret coding well explained, such ramping signals, scale amplitude phase release, inhibitory autoreceptors facilitating postinhibitory rebound, etc. This study aims elucidate working system physiological states reinforcement, research foundation

Language: Английский

Mechanisms of neuromodulatory volume transmission DOI Creative Commons
Özge Demet Özçete, Aditi Banerjee, Pascal S. Kaeser

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(11), P. 3680 - 3693

Published: May 24, 2024

Abstract A wealth of neuromodulatory transmitters regulate synaptic circuits in the brain. Their mode signaling, often called volume transmission, differs from classical transmission important ways. In vesicles rapidly fuse response to action potentials and release their transmitter content. The are then sensed by nearby receptors on select target cells with minimal delay. Signal is restricted contacts typically occurs within ~1 ms. Volume doesn’t rely contact sites main monoamines neuropeptides, neuromodulators It less precise than underlying molecular mechanisms spatiotemporal scales not well understood. Here, we review literature raise scientific questions that should be addressed years ahead. We define five domains which systems can differ one another. These (1) innervation patterns firing properties, (2) synthesis loading into different types vesicles, (3) architecture distribution sites, (4) diffusion, degradation, reuptake, (5) receptor positioning cells. discuss these for dopamine, a well-studied monoamine, compare dopamine norepinephrine serotonin. include assessments neuropeptide signaling central acetylcholine transmission. Through this review, provide cellular framework This mechanistic knowledge essential how control behavior health disease understand they modulated medical treatments drugs abuse.

Language: Английский

Citations

22
Dopamine dynamics are dispensable for movement but promote reward responses DOI
Xintong Cai, Changliang Liu, Iku Tsutsui‐Kimura

et al.

Nature, Journal Year: 2024, Volume and Issue: 635(8038), P. 406 - 414

Published: Oct. 16, 2024

Language: Английский

Citations

12
Morphological and functional decline of the SNc in a model of progressive parkinsonism DOI Creative Commons

Jacob M. Muñoz,

John T. Williams, Joseph J. Lebowitz

et al.

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 29, 2025

Abstract The motor symptoms of Parkinson’s Disease are attributed to the degeneration dopamine neurons in substantia nigra pars compacta (SNc). Previous work MCI-Park mouse model has suggested that loss somatodendritic transmission predicts development deficits. In current study, brain slices from mice were used investigate signaling SNc prior and through onset movement Electrophysiological properties impaired by p30 somatic volume was decreased at all time points. D2 receptor activated potassium evoked quinpirole present initially, but declined after p30. contrast, D2-IPSCs absent decrease GPCR-mediated inhibition met with increased spontaneous GABA A signaling. Dendro-dendritic synapses identified as an early locus dysfunction response bioenergetic decline suggest dendritic release sites may contribute induction degeneration.

Language: Английский

Citations

1
Synaptotagmin-1-dependent phasic axonal dopamine release is dispensable for basic motor behaviors in mice DOI Creative Commons
Benoît Delignat‐Lavaud,

Jana Kano,

Charles Ducrot

et al.

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

Published: July 11, 2023

Abstract In Parkinson’s disease (PD), motor dysfunctions only become apparent after extensive loss of DA innervation. This resilience has been hypothesized to be due the ability many behaviors sustained through a diffuse basal tone DA; but experimental evidence for this is limited. Here we show that conditional deletion calcium sensor synaptotagmin-1 (Syt1) in neurons (Syt1 cKO mice) abrogates most activity-dependent axonal release striatum and mesencephalon, leaving somatodendritic (STD) intact. Strikingly, Syt1 mice showed intact performance multiple unconditioned DA-dependent tasks even task evaluating conditioned motivation food. Considering extracellular levels were unchanged, our findings suggest dispensable such they can by DA. Taken together, reveal striking functions context near-abolition phasic release, shedding new light on why innervation required PD.

Language: Английский

Citations

19
Synaptotagmin-7 Counteracts Short-Term Depression during Phasic Dopamine Release DOI Creative Commons
Joseph J. Lebowitz,

Sarah A. Kissiwaa,

Kim A. Engeln

et al.

eNeuro, Journal Year: 2024, Volume and Issue: 11(3), P. ENEURO.0501 - 23.2024

Published: Feb. 16, 2024

Dopamine neurons switch from tonic pacemaker activity to high-frequency bursts in response salient stimuli. These lead superlinear increases dopamine release, and the degree of this increase is highly dependent on firing frequency. The superlinearity frequency dependence release implicate short-term plasticity processes. presynaptic Ca 2+ -sensor synaptotagmin-7 (SYT7) has suitable properties mediate such been implicated regulating somatodendritic compartments. Here, we use a genetically encoded sensor whole-cell electrophysiology Syt7 KO mice determine how SYT7 contributes both axonal release. We find that mediates hidden component facilitation terminals can be unmasked by lowering initial probability or predepressing synapses with low-frequency stimulation. Depletion increased depression reduced during stimulations mimic vivo firing. Recordings D2-mediated inhibitory postsynaptic currents substantia nigra pars compacta (SNc) confirmed similar role for Our results indicate drives which may explain signaling seen vivo.

Language: Английский

Citations

4
Clinicopathological features and prognostic significance of SYT8 in patients with colorectal cancer who received curative surgery DOI Open Access

Jin Zhu,

Jiarong Shang, Yuan Li

et al.

Gastrointestinal Tumors, Journal Year: 2025, Volume and Issue: 12(1), P. 0 - 0

Published: Jan. 1, 2025

Language: Английский

Citations

0
Biomarkers of mature neuronal differentiation and related diseases DOI Creative Commons
Xiaodong Yuan, Wen Li, Yan Qi

et al.

Future Science OA, Journal Year: 2024, Volume and Issue: 10(1)

Published: Oct. 21, 2024

The nervous system regulates perception, cognition and behavioral responses by serving as the body's primary communication for receiving, regulating transmitting information. Neurons are fundamental structures units of system. Their differentiation maturation processes rely on expression specific biomarkers. Neuron-specific intracellular markers can be used to determine degree neuronal maturation. Neuronal cytoskeletal proteins dictate shape structure neurons, while synaptic plasticity signaling intricately associated with markers. Furthermore, abnormal levels biomarkers serve diagnostic indicators diseases. This article reviews mature their relationship

Language: Английский

Citations

2
Protein composition of axonal dopamine release sites in the striatum DOI Creative Commons
Lauren Kershberg, Aditi Banerjee, Pascal S. Kaeser

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Dec. 29, 2022

Dopamine is an important modulator of cognition and movement. We recently found that evoked dopamine secretion fast relies on active zone-like release sites. Here, we used in vivo biotin identification (iBioID) proximity proteomics mouse striatum to assess which proteins are present at these Using three site baits, identified enriched over the general axonal protein content, they fell into several categories, including zone, Ca 2+ regulatory, synaptic vesicle proteins. also detected many not previously associated with vesicular exocytosis. Knockout presynaptic organizer RIM strongly decreased hit number obtained iBioID, while Synaptotagmin-1 knockout did not. α-Synuclein, a linked Parkinson’s disease, was sites, its enrichment lost both tested mutants. conclude organizes scaffolded sites provide proteomic assessment composition

Language: Английский

Citations

10
Unraveling the Potential of EphA4: A Breakthrough Target and Beacon of Hope for Neurological Diseases DOI
M. R. Verma, Manjeet Chopra, Hemant Kumar

et al.

Cellular and Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 43(7), P. 3375 - 3391

Published: July 21, 2023

Language: Английский

Citations

5
Synaptotagmin-1-dependent phasic axonal dopamine release is dispensable for basic motor behaviors in mice DOI Creative Commons
Benoît Delignat‐Lavaud,

Jana Kano,

Charles Ducrot

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Sept. 16, 2021

Abstract In Parkinson’s disease (PD), motor dysfunctions only become apparent after extensive loss of DA innervation. This resilience has been hypothesized to be due the ability many behaviors sustained through a diffuse basal tone DA; but experimental evidence for this is limited. Here we show that conditional deletion calcium sensor synaptotagmin-1 (Syt1) in neurons (Syt1 cKO mice) abrogates most activity-dependent axonal release striatum and mesencephalon, leaving somatodendritic (STD) intact. Strikingly, Syt1 mice showed intact performance multiple unconditioned DA-dependent tasks even task evaluating conditioned motivation food. Considering extracellular levels were unchanged, our findings suggest dispensable such they can by DA. Taken together, reveal striking functions context near-abolition phasic release, shedding new light on why innervation required PD.

Language: Английский

Citations

10