Springer eBooks, Journal Year: 2022, Volume and Issue: unknown, P. 575 - 598
Published: Jan. 1, 2022
Language: Английский
Neuron, Journal Year: 2022, Volume and Issue: 110(18), P. 2949 - 2960.e4
Published: Aug. 4, 2022
Transmission from striatal cholinergic interneurons (CINs) controls dopamine release through nicotinic acetylcholine receptors (nAChRs) on dopaminergic axons. Anatomical studies suggest that terminals signal predominantly non-synaptic volume transmission. However, the influence of transmission electrical signaling in axons remains unclear. We examined axo-axonal CINs onto using perforated-patch recordings, which revealed rapid spontaneous EPSPs with properties characteristic fast synapses. Pharmacology showed axonal (axEPSPs) were mediated primarily by high-affinity α6-containing receptors. Remarkably, axEPSPs triggered action potentials, suggesting these perform integration to convert synaptic input into spiking, a function associated somatodendritic compartments. investigated cross-species validity recording macaque putamen and found similar axEPSPs. Thus, we reveal synaptic-like neurotransmission underlies axons, supporting idea can occur independently somatic firing provide distinct signaling.
Language: Английский
Citations
67
Antioxidants, Journal Year: 2022, Volume and Issue: 11(1), P. 170 - 170
Published: Jan. 17, 2022
Oxidative stress and neuroinflammation are common bases for disease onset progression in many neurodegenerative diseases. In Parkinson disease, which is characterized by the degeneration of dopaminergic neurons resulting dopamine depletion, pathogenesis differs between hereditary solitary forms often unclear. addition to pathogenicity alpha-synuclein as a pathological marker, involvement itself its interactions with glial cells (astrocyte or microglia) have attracted attention. Pacemaking activity, hallmark neurons, essential homeostatic maintenance adequate concentrations synaptic cleft, but it imposes burden on mitochondrial oxidative glucose metabolism, leading reactive oxygen species production. Astrocytes provide endogenous neuroprotection brain producing releasing antioxidants response stress. Additionally, protective function astrocytes can be modified microglia. Some types microglia themselves thought exacerbate pro-inflammatory factors (M1 microglia). Although these inflammatory may further trigger conversion astrocytes, induce astrocytic neuroprotective effects (A2 astrocytes) simultaneously. Interestingly, both express receptors, upregulated presence neuroinflammation. The anti-inflammatory receptor stimulation also attracting attention because functions greatly affected depletion therapeutic replacement disease. this review article, we will focus antioxidative their synergism dopamine.
Language: Английский
Citations
44
AJP Cell Physiology, Journal Year: 2022, Volume and Issue: 323(2), P. C439 - C460
Published: June 15, 2022
G protein-gated inwardly rectifying K + (GIRK/Kir3) channels exert a critical inhibitory influence on neurons. Neuronal GIRK mediate the protein-dependent, direct/postsynaptic effect of many neurotransmitters including γ-aminobutyric acid (GABA), serotonin, dopamine, adenosine, somatostatin, and enkephalin. In addition to their complex regulation by proteins, neuronal channel activity is sensitive phosphatidylinositol 4,5-bisphosphate (PIP 2 ), phosphorylation, regulator protein signaling (RGS) intracellular Na Ca 2+ , cholesterol. The application genetic viral manipulations in rodent models, together with recent progress development modulators, has increased our understanding physiological behavioral impact channels. Work models also revealed that modified, transiently or persistently, various stimuli exposure drugs abuse, changes patterns, aversive experience. A growing body preclinical clinical evidence suggests dysregulation contributes neurological diseases disorders. primary goals this review are highlight fundamental principles biology, mechanisms plasticity, nascent landscape pharmacology, potential relevance pathophysiology treatment
Language: Английский
Citations
40
Cell Reports, Journal Year: 2024, Volume and Issue: 43(3), P. 113834 - 113834
Published: March 1, 2024
Striatal dopamine axons co-release and gamma-aminobutyric acid (GABA), using GABA provided by uptake via transporter-1 (GAT1). Functions of are poorly understood. We asked whether co-released autoinhibits release axonal type A receptors (GABAARs), complementing established inhibition acting at D2 autoreceptors. show that express α3-GABAAR subunits in mouse striatum. Enhanced evoked single-pulse optical stimulation striatal slices with GABAAR antagonism confirms an endogenous tone limits release. Strikingly, additional inhibitory component is seen when multiple pulses used to mimic phasic activity, revealing the role GABAAR-mediated autoinhibition This autoregulation lost conditional GAT1-knockout mice lacking co-release. Given faster kinetics ionotropic GABAARs than G-protein-coupled autoreceptors, our data reveal a mechanism whereby acts as first responder dampen phasic-to-tonic signaling.
Language: Английский
Citations
15
Frontiers in Psychiatry, Journal Year: 2021, Volume and Issue: 12
Published: Dec. 16, 2021
Serotonin is a key neurotransmitter that implicated in wide variety of behavioral and cognitive phenotypes. Originating the raphe nuclei, 5-HT neurons project widely to innervate many brain regions functions. During development brain, as serotonin axons regions, there evidence plays roles wiring developing both by modulating innervation influencing synaptic organization within corticolimbic structures. These actions are mediated 14 different receptors, with region- cell-specific patterns expression. More recently, role system re-organization during adulthood has been suggested. The have unusual capacity regrow reinnervate following insults such injury, chronic stress, or altered result disconnection often cause depression, anxiety, impairment. Chronic treatment antidepressants amplify action, selective reuptake inhibitors (SSRIs), appears accelerate rewiring mechanisms may be critical improvements induced these models. In this review, we survey possible receptor could mediate assess 5-HT-mediated impacting recovery from mental illness. By amplifying 5-HT-induced processes using SSRIs agonists, more rapid effective treatments for injury-induced illness impairment achieved.
Language: Английский
Citations
51
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
Published: Feb. 10, 2025
Neuronal function is intimately tied to axodendritic polarity. Neurotransmitter release, for example, usually the role of axon. There are widespread exceptions this rule, however, including many mammalian neuronal types that can release neurotransmitter from their dendrites. In mouse olfactory bulb, closely related subclasses dopaminergic interneuron differ markedly in polarity, with one subtype lacking an axon entirely. These axon-bearing and anaxonic have distinct developmental profiles sensory responses, but how fundamental polarity differences translate functional outputs remains entirely unknown. Here, we provide anatomical evidence strategies among these subtypes: cells dendrites, while neurons exclusively intermittently myelinated structural linked a clear distinction: anaxonic, not capable self-inhibition. Our findings suggest variations produce striking distinctions outputs, even may play separate roles information processing.
Language: Английский
Citations
0
Published: Feb. 10, 2025
Neuronal function is intimately tied to axodendritic polarity. Neurotransmitter release, for example, usually the role of axon. There are widespread exceptions this rule, however, including many mammalian neuronal types that can release neurotransmitter from their dendrites. In mouse olfactory bulb, closely related subclasses dopaminergic interneuron differ markedly in polarity, with one subtype lacking an axon entirely. These axon-bearing and anaxonic have distinct developmental profiles sensory responses, but how fundamental polarity differences translate functional outputs remains entirely unknown. Here, we provide anatomical evidence strategies among these subtypes: cells dendrites, while neurons exclusively intermittently myelinated structural linked a clear distinction: anaxonic, not capable self-inhibition. Our findings suggest variations produce striking distinctions outputs, even may play separate roles information processing.
Language: Английский
Citations
0
Neurochemistry International, Journal Year: 2022, Volume and Issue: 162, P. 105465 - 105465
Published: Dec. 21, 2022
Parkinson's disease is the second most common neurodegenerative which characterized by selective degeneration of dopaminergic neurons in substantia nigra pars compacta. The intrinsic neuronal firing activity critical for functional organization brain and specific deficits may be associated with different disorders. It known that surviving exhibit altered activity, such as decreased spontaneous frequency, reduced number increased burst disease. Several ionic mechanisms are involved changed under parkinsonian state. In this review, we summarize changes well possible This review let us clearly understand involvement
Language: Английский
Citations
17
Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 116907 - 116907
Published: March 1, 2025
Ischemic stroke is a debilitating condition characterized by high morbidity, disability, recurrence, and mortality rates on global scale, posing significant threat to public health economic stability. Extensive research has thoroughly explored the molecular mechanisms underlying ischemic stroke, elucidating strong association between soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor proteins (SNAREs) pathogenesis of this condition. SNAREs, class highly conserved involved in membrane fusion, play crucial role modulating neuronal information transmission promoting myelin formation central nervous system (CNS). Preventing SNARE complex formation, malfunctions SNARE-dependent exocytosis, altered regulation SNARE-mediated vesicle fusion are linked excitotoxicity, endoplasmic reticulum (ER) stress, programmed cell death (PCD) stroke. However, its remain unclear. This study conducts comprehensive review existing literature proteins, encompassing structure, classification, expression family, as well assembly - disassembly cycle complexes their physiological roles CNS. We examine which SNAREs contribute pathological progression associated risk factors (hypertension, hyperglycemia, dyslipidemia, atherosclerosis). Furthermore, our findings highlight promise viable target for pharmacological interventions treatment
Language: Английский
Citations
0