A5061258414- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neural Engineering
- Neurological disorders and treatments
- Neural dynamics and brain function
- Electrochemical Analysis and Applications
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Genetic Neurodegenerative Diseases
- Neurogenesis and neuroplasticity mechanisms
- Conducting polymers and applications
- Pancreatic function and diabetes
- Electrochemical sensors and biosensors
- Molecular Biology Techniques and Applications
- Advanced Electron Microscopy Techniques and Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Barrier Structure and Function Studies
- Cellular transport and secretion
- Synthesis of heterocyclic compounds
- Neural and Behavioral Psychology Studies
- Photoreceptor and optogenetics research
- Adipose Tissue and Metabolism
- Pharmacological Receptor Mechanisms and Effects
University of Oxford
2014-2024
Research Network (United States)
2023-2024
Parkinson's UK
2016-2023
Molecular Devices (United Kingdom)
2023
Pediatrics and Genetics
2015-2016
Key points The voltage‐gated Ca 2+ channels (VGCCs) that catalyse striatal dopamine transmission are critical to function and might prime subpopulations of neurons for parkinsonian degeneration. However, the VGCCs operate on mesostriatal axons incompletely defined; previous studies encompassed cholinergic interneurons strongly influence transmission. We define multiple types axonal extend beyond classic presynaptic N/P/Q include T‐ L‐types. reveal differences in VGCC between mouse axon...
Significance Dopaminergic neurons in the brain control voluntary movement and a variety of cognitive functions, including reward–motivation mechanisms, mood regulation, addiction, memory. Understanding how dopaminergic neurons' phenotype function are maintained throughout their life span is great importance light diverse roles that they play. Transcription factors FOXA1/2 development then retain expression adult neurons. The role these during well established, but meaning still not...
Striatal dopamine (DA) is a major player in action selection and reinforcement. DA release under strong local control by striatal ACh acting at axonal nicotinic receptors (nAChRs) on axons. nAChRs have been shown to how released response ascending activity from neurons, they also directly drive following synchronized small cholinergic network. The source of has thought arise solely intrinsic interneurons (ChIs), but recent findings identified inputs striatum brainstem nuclei, the...
Mesostriatal dopaminergic neurons possess extensively branched axonal arbours. Whether action potentials are converted to dopamine output in the striatum will be influenced dynamically and critically by properties mechanisms that poorly understood. Here, we address roles for governing release probability activity determining short-term plasticity of release, using fast-scan cyclic voltammetry ex vivo mouse striatum. We show brief facilitation longer short term depression only weakly...
Mutations in leucine-rich repeat kinase 2 (LRRK2) lead to late-onset, autosomal dominant Parkinson's disease, characterized by the degeneration of dopamine neurons substantia nigra pars compacta, a deficit neurotransmission and development motor non-motor symptoms. The most prevalent disease LRRK2 mutations are located (G2019S) GTPase (R1441C) encoding domains LRRK2. To better understand sequence events that progressive neurophysiological deficits vulnerable circuits we have generated...
The mammalian striatum has a topographical organization of input–output connectivity, but complex internal, nonlaminar neuronal architecture comprising projection neurons two types interspersed among multiple interneuron and potential local neuromodulators. From this cellular melange arises biochemical compartmentalization areas termed striosomes extrastriosomal matrix. functions these compartments are poorly understood might confer distinct features to striatal signal processing be...
Abstract Striatal dopamine (DA) is critical for action and learning. Recent data show that DA release under tonic inhibition by striatal GABA. Ambient GABA tone on projection neurons can be determined plasma membrane uptake transporters (GATs) located astrocytes neurons. However, whether GATs determine output are unknown. We reveal in mouse dorsolateral striatum, but not nucleus accumbens core, governed GAT-1 GAT-3. These partly localized to astrocytes, enriched striatum compared core. In a...
Striatal dopamine transporters (DAT) powerfully regulate signaling, and can contribute risk to degeneration in Parkinson’s disease (PD). DATs interact with the neuronal protein α-synuclein, which is associated etiology molecular pathology of idiopathic familial PD. Here, we tested whether DAT function governing (DA) uptake release modified a human-α-synuclein-overexpressing ( SNCA -OVX) transgenic mouse model early Using fast-scan cyclic voltammetry (FCV) ex vivo acute striatal slices detect...
Abstract Oligodendrocyte progenitor cells (OPCs) receive synaptic innervation from glutamatergic and GABAergic axons can be dynamically regulated by neural activity, resulting in activity-dependent changes patterns of axon myelination. However, it remains unclear to what extent other types neurons may innervate OPCs. Here, we provide evidence implicating midbrain dopamine the oligodendrocyte lineage anterior corpus callosum nearby white matter tracts male female adult mice. Dopaminergic...
The calcium-binding protein calbindin-D28K, or calb1, is expressed at higher levels by dopamine (DA) neurons originating in the ventral tegmental area (VTA) than adjacent substantia nigra pars compacta (SNc). Calb1 has received attention for a potential role neuroprotection Parkinson's disease. underlying physiological roles calb1 are incompletely understood. We used cre-loxP technology to knock down mouse DA test whether governs axonal release of striatum, detected using fast-scan cyclic...
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Neuronal T-type voltage-gated Ca(2+) channels are reported to have physiological roles that include regulation of burst firing, oscillations, and neurotransmitter release. These often exposed experimentally by blocking with micromolar Ni(2+). We used Ni(2+) explore the role axonal in dopamine (DA) release mouse striatum, but identified significant off-target effects on DA uptake. (100 μM) reversibly increased electrically evoked markedly extended its extracellular lifetime, detected using...
This collection contains five protocols detailing methods used in Brimblecombe, K.R. et al. (2023) Inhibition of striatal dopamine release by the L-type calcium channel inhibitor isradipine, co-varies with risk factors for Parkinson’s.
Abstract Mesostriatal DA neurons possess extensively branched axonal arbours. Whether action potentials are converted to output in striatum will be influenced dynamically and critically by properties mechanisms that poorly understood. We addressed the roles for governing release probability activity determining short-term plasticity of release, using fast-scan cyclic voltammetry ex vivo mouse striatum. Brief facilitation (STF) longer depression (STD) were only weakly dependent on level...
Abstract Ca 2+ entry into nigrostriatal dopamine (DA) neurons and axons via L-type voltage-gated channels (LTCCs) contributes respectively to pacemaker activity DA release, has long been thought contribute vulnerability degeneration in Parkinson’s disease. LTCC function is greater from substantia nigra pars compacta than ventral tegmental area, but this not explained by channel expression level. We tested the hypothesis that LTCC-control of release governed rather local mechanisms, focussing...
This collection contains three protocols detailing methods used in Brimblecombe, K.R. et al. (2023) Inhibition of striatal dopamine release by the L-type calcium channel inhibitor isradipine, co-varies with risk factors for Parkinson’s.
This protocol is to assess whether a drug changes the dopamine concentration released following single pulse (1p) electrical stimulation.
TBD
This collection contains three protocols detailing methods used in Brimblecombe, K.R. et al. (2023) Inhibition of striatal dopamine release by the L-type calcium channel inhibitor isradipine, co-varies with risk factors for Parkinson’s.