A5056445708- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Neural dynamics and brain function
- Parkinson's Disease Mechanisms and Treatments
- Nerve injury and regeneration
- Receptor Mechanisms and Signaling
- Circadian rhythm and melatonin
- Neuroscience and Neural Engineering
- Tryptophan and brain disorders
- Neurological disorders and treatments
- Alzheimer's disease research and treatments
- Cellular transport and secretion
- Memory and Neural Mechanisms
- Protein Degradation and Inhibitors
- Advanced Nanomaterials in Catalysis
- Spectroscopy Techniques in Biomedical and Chemical Research
- Sleep and Wakefulness Research
- Neurogenesis and neuroplasticity mechanisms
- Gold and Silver Nanoparticles Synthesis and Applications
- Fatty Acid Research and Health
- Photoreceptor and optogenetics research
- Peroxisome Proliferator-Activated Receptors
Centre Hospitalier de l’Université de Montréal
2023-2024
Université de Montréal
2019-2023
McGill University
2023
Research Network (United States)
2023
Hôpital du Sacré-Cœur de Montréal
2023
Centre Intégré Universitaire de Santé et de Services Sociaux du Centre-Sud-de-l'Île-de-Montréal
2023
Canadian Sleep & Circadian Network
2023
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopamine (DA) neurons in substantia nigra pars compacta (SNc). Rare genetic mutations genes such as Parkin, Pink1, DJ-1, α-synuclein, LRRK2 and GBA are found to be responsible for about 15% cases. A key unanswered question PD pathophysiology why would these mutations, impacting basic cellular processes mitochondrial function neurotransmission, lead selective degeneration SNc DA neurons? We previously showed...
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)...
A subset of adult ventral tegmental area dopamine (DA) neurons expresses vesicular glutamate transporter 2 (VGluT2) and releases as a second neurotransmitter in the striatum, while only few substantia nigra DA have this capacity. Recent work showed that cellular stress created by neurotoxins such MPTP 6-hydroxydopamine can upregulate VGluT2 surviving neurons, suggesting possibility role cell survival, although high level overexpression could be toxic to neurons. Here we examined upregulation...
Chemical neurotransmission typically occurs through synapses. Previous ultrastructural examinations of monoamine neuron axon terminals often failed to identify a pre- and postsynaptic coupling, leading the concept "volume" transmission. Whether this results from intrinsic properties these neurons remains undefined. We find that dopaminergic in vitro establish distinctive axonal arbor compared glutamatergic or GABAergic both size propensity avoid direct contact with target neurons. While most...
Abstract Background Soluble amyloid-beta oligomers (Aβo) begin to accumulate in the human brain one two decades before a clinical diagnosis of Alzheimer’s disease (AD). The literature supports that soluble Aβo are implicated synapse and neuronal losses regions such as hippocampus. This region importantly contributes explicit memory, first type memory affected AD. During AD preclinical prodromal stages, people also experiencing wake/sleep alterations insomnia (e.g., difficulty initiating...
Dopamine (DA) neurons can release DA not just from axon terminals, but also their somatodendritic (STD) compartment through a mechanism that is still incompletely understood. Using voltammetry in mouse mesencephalic brain slices, we find STD has low capacity and shows calcium sensitivity comparable to of axonal release. We the molecular differs with regard implication synaptotagmin (Syt) sensors. While individual constitutive knockout Syt4 or Syt7 sufficient reduce release, removal both...
Midbrain dopamine (DA) neurons are key regulators of basal ganglia functions. The axonal domain these is highly complex, with a large subset non-synaptic release sites and smaller synaptic terminals from which in addition to DA, glutamate or GABA also released. molecular mechanisms regulating the connectivity DA their neurochemical identity unknown. An emerging literature suggests that neuroligins, trans-synaptic cell adhesion molecules, regulate both neuron neurotransmission. However,...
ABSTRACT The symptomatology of Alzheimer’s disease (AD) includes cognitive deficits and sleep disturbances. Recent findings suggest the involvement dysfunctions in lipid metabolism, such as oleic acid build-up, brain AD patients animal models. In addition, inhibition stearoyl-CoA desaturase (SCD), a lipid-converting enzyme, was shown to restore memory triple transgenic (3xTg)-AD mice. brain, astrocytes regulate synthesis specific lipids. Alterations their function were reported models, have...
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)...
ABSTRACT Chemical neurotransmission in the brain typically occurs through synapses, which are structurally and functionally defined as sites of close apposition between an axon terminal a postsynaptic domain. Ultrastructural examinations terminals established by monoamine neurons often failed to identify similar tight pre- coupling, giving rise concept “diffuse” or “volume” transmission. Whether this results from intrinsic properties such modulatory remains undefined. Using efficient...
Plasmonic nanostructures have found increasing utility due to the increased popularity that surface-enhanced Raman scattering (SERS) has achieved in recent years. SERS been incorporated into an ever-growing list of applications, with bioanalytical and physiological analyses having emerged as two most popular. Thus far, transition from studies cultured cells involving tissue gradual limited. In cases, measurements more intact involved nanoparticles distributed throughout or localized specific...
ABSTRACT Dopamine (DA) neurons can release DA not just from axon terminals, but also their somatodendritic (STD) compartment thought a mechanism that is still incompletely understood. Using voltammetry in mouse mesencephalic brain slices, we find STD has low capacity, stable response to electrical optogenetic train pulses and shows calcium sensitivity comparable of axonal release. It strikingly more resilient compared 6‐ hydroxydopamine model Parkinson’s disease plasticity. We the molecular...
Summary Midbrain dopamine (DA) neurons are key regulators of basal ganglia functions. The axonal domain these is highly complex, with a large subset non-synaptic release sites and smaller synaptic terminals from which glutamate or GABA released. molecular mechanisms regulating the connectivity DA their neurochemical identity unknown. Here we tested hypothesis that trans-synaptic cell adhesion molecules neurexins (Nrxns) regulate neuron neurotransmission. Conditional deletion all Nrxns in...
ABSTRACT In Parkinson’s disease, the most vulnerable neurons are found in ventral tier of substantia nigra (SN), while adjacent dopamine (DA) tegmental area (VTA) mostly spared. Although a significant subset adult VTA DA expresses Vglut2 , vesicular glutamate transporter, and release as second neurotransmitter striatum, only very few SN have this capacity. Previous work has demonstrated that lesions created by neurotoxins such MPTP 6-hydroxydopamine (6-OHDA) can upregulate expression...
ABSTRACT Background D-amphetamine maintenance therapy shows promise as a treatment for people with cocaine addiction. Preclinical studies using Long Access (LgA) self-administration procedures suggest may act by preventing tolerance to cocaine’s effects at the dopamine transporter (DAT). However, Intermittent (IntA) better reflects human patterns of use, is especially effective in promoting addiction-relevant behaviors, and instead tolerance, produces psychomotor, incentive, neural...
ABSTRACTCircadian rhythms originate from molecular feedback loops. In mammals, the transcription factors CLOCK and BMAL1 act on regulatory elements (i.e. E-boxes) to shape biological functions in a rhythmic manner. The EPHA4 receptor its ligands Ephrins (EFN) are cell adhesion molecules regulating neurotransmission neuronal morphology. Previous studies showed presence of E-boxes genes EphA4 specific Ephrins, that knockout mice have an altered circadian rhythm locomotor activity. We thus...
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 cKODA mice) abrogates most activity-dependent axonal release striatum and mesencephalon, leaving somatodendritic (STD) intact....
ABSTRACT The dopamine transporter (DAT) plays a crucial role in regulating the brain’s (DA) homeostasis. Atypical DAT deficiency syndrome (DTSD) is disease characterized by early-onset parkinsonism and comorbid psychiatric symptoms, but pathobiological processes that link dysfunction to both symptoms are unknown. Here, we present genetic mouse model of atypical DTDS expresses two coding variants, DAT-I312F DAT-D421N, derived from patient diagnosed with ADHD parkinsonism. Phenotypic...