A5064840346- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Axon Guidance and Neuronal Signaling
- Neurogenesis and neuroplasticity mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Memory and Neural Mechanisms
- Receptor Mechanisms and Signaling
- Genetic Neurodegenerative Diseases
- Sleep and Wakefulness Research
- Nerve injury and regeneration
- Mitochondrial Function and Pathology
- Neural dynamics and brain function
- Zebrafish Biomedical Research Applications
- Alzheimer's disease research and treatments
- Wnt/β-catenin signaling in development and cancer
- Neuroscience and Neural Engineering
- Advanced Neuroimaging Techniques and Applications
- Neuroscience of respiration and sleep
- Medicinal Plants and Neuroprotection
- Obsessive-Compulsive Spectrum Disorders
- Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Nuclear Receptors and Signaling
- MicroRNA in disease regulation
- Cancer-related gene regulation
The University of Sydney
2021-2025
UNSW Sydney
2014-2024
University Medical Center Utrecht
2009-2015
Utrecht University
2009
The Netherlands Cancer Institute
2008
Monoaminergic neurons [serotonergic (5-HT) and dopaminergic (mdDA)] in the brainstem project axons along anterior-posterior axis. Despite their important physiological functions implication disease, molecular mechanisms that dictate formation of these projections axis remain unknown. Here we reveal a novel requirement for Wnt/planar cell polarity signaling organization monoaminergic system. We find 5-HT mdDA express core planar components Frizzled3, Celsr3, Vangl2. In addition, show guidance...
The subthalamic nucleus (STN) is a major neuromodulation target for the alleviation of neurological and neuropsychiatric symptoms using deep brain stimulation (DBS). STN-DBS today applied as treatment in Parkinson´s disease, dystonia, essential tremor, obsessive-compulsive disorder (OCD). also shows promise refractory Tourette syndrome. However, internal organization STN has remained elusive challenges researchers clinicians: How can this small structure engage multitude functions that...
Dopaminergic neurons in the mesodiencephalon (mdDA neurons) make precise synaptic connections with targets forebrain via mesostriatal, mesolimbic, and mesoprefrontal pathways. Because of functional importance these remarkably complex ascending axon pathways their implication human disease, mechanisms underlying development are considerable interest. Despite extensive vitro studies, molecular determinants that ensure perfect formation vivo remain mostly unknown. Here, we determine embryonic...
Ventral pallidum (VP) is a well-established locus for the reinforcing effects of drugs abuse and reinstatement drug seeking. However, VP neurons are at origin multiple output pathways, with strong projections to ventral tegmental area (VTA), subthalamic nucleus (STN), lateral hypothalamus, among others, roles these pathways in seeking remain poorly understood. Here we addressed issues using combination neuroanatomical tracing chemogenetic approaches. First, dual-retrograde tracing, show that...
The mesolimbic dopamine system comprises distinct compartments supporting different functions in learning and motivation. Less well understood is how complex addiction-related behaviors emerge from activity patterns across these compartments. Here we show forms of relapse to alcohol-seeking male rats are assembled the VTA nucleus accumbens. First, used chemogenetic approaches a causal role for TH neurons two alcohol-seeking: renewal (context-induced reinstatement) reacquisition. Then, using...
The ventral pallidum (VP) is a key node in the neural circuits controlling relapse to drug seeking. How this role relates different VP cell types and their projections poorly understood. Using male rats, we show how forms of alcohol-seeking are assembled from lateral hypothalamus (LH) tegmental area (VTA). RNAScope situ hybridization characterize activity during provoked by renewal (context-induced reinstatement), found that Gad1 parvalbumin (PV), but not vGlut2, neurons relapse-associated...
Parkinson's disease (PD) is a neurological disorder with motor dysfunction and number of psychiatric symptoms. Symptoms such as anxiety cognitive deficits emerge prior to symptoms persist over time. There are limited treatments targeting PD Emerging studies reveal that the gut microbe altered in patients. Here we assessed effect probiotic treatment rat model PD. We used neurotoxin (6-hydroxydopamine, 6-OHDA) preclinical examine impact (Lacticaseibacillus rhamnosus HA-114) on memory. Rats...
The ubiquitin kinase-ligase pair PINK1-PRKN recognizes and transiently labels damaged mitochondria with phosphorylated at Ser65 (p-S65-Ub) to mediate their selective degradation (mitophagy). Complete loss of PINK1 or PRKN function unequivocally leads early-onset Parkinson disease, but it is debated whether impairments in mitophagy contribute disease later life. While the pathway has been extensively studied cell culture upon acute massive mitochondrial stress, basal levels activation under...
Abstract Alcohol use disorder (AUD) is characterized by cycles of abuse, withdrawal, and relapse. Neuroadaptations in the basal ganglia are observed AUD; specifically putamen, globus pallidus (GP), ventral pallidum (VP). These regions associated with habit formation, drug‐seeking behaviors, reward processing. While previous studies have shown crucial role glial cells drug seeking, it remains unknown whether altered AUD. Glial GP, VP were examined human post‐mortem tissue AUD alcohol...
The striatum is a large brain nucleus with an important role in the control of movement and emotions. Medium spiny neurons (MSNs) are striatal output forming prominent descending axon tracts that target different nuclei. However, how MSN forebrain develop remains poorly understood. Here, we implicate Wnt binding receptor Frizzled3 several uncharacterized aspects pathway formation [i.e., anterior–posterior guidance axons their subsequent growth into globus pallidus (GP), (intermediate)...
Parkinsons disease is considered biologically a neuronal alpha synuclein disease, largely ignoring the more widespread deposition that occurs in astrocytes. Recent single cell transcriptomics have identified early astrocytic differences both and mouse models with an increase reactive astrocytes associated proteostasis. To identify whether accumulate before or after neurons, present study histologically assessed accumulation M83 A53T transgenic model of prior to significant accumulation. The...
Ryk is an atypical transmembrane receptor tyrosine kinase that has been shown to play multiple roles in development through the modulation of Wnt signaling. Within developing ventral midbrain (VM), Wnts have contribute proliferation, differentiation, and connectivity dopamine (DA) neurons; however, Wnt-related receptors regulating these events remain less well described. In light established Wnt5a dopaminergic (regulating DA differentiation as axonal growth repulsion), its interaction with...
Parkinson's disease (PD) is a progressive neurodegenerative disorder, pathologically hallmarked by the loss of dopamine neurons in substantia nigra (SN) and alpha-synuclein aggregation. Deep brain stimulation (DBS) subthalamic nucleus (STN) common target to treat motor symptoms PD. However, we have less understanding cellular changes STN during PD, impact DBS on SN limited. We examined PD patients with without STN-DBS treatment. Post-mortem tissues from 6 non-STN-DBS patients, 5 age-matched...
Two experiments used vivo morpholinos to assess the role of orexin/hypocretin in ABA renewal extinguished alcohol seeking. Rats were trained respond for alcoholic beer a distinctive context, A, and then second B. When rats tested extinction ABB, responding was low but when they training ABA, significantly higher. Microinjection an antisense morpholino into LH reduced protein expression had no effect on seeking (Experiment 1). higher dose also this not selective yielded significant reduction...
The ventral pallidum (VP) is a key component of the neural circuitry mediating relapse to drug seeking, but critical afferent pathways VP recruited during remain poorly understood. We studied role nucleus accumbens core (AcbC) → pathway in ABA renewal and reacquisition alcohol seeking. Rats received application adenoviral vectors encoding eYFP, ChR2(H134R), or eNpHr3.0 AcbC implantation fiber optic cannulas into permit photostimulation terminals there. were then trained self-administer...
Parkinson's disease (PD) is a neurodegenerative disorder characterized by range of motor symptoms. Treatments are focused on dopamine replacement therapy or deep brain stimulation (DBS). The subthalamic nucleus (STN) common target for DBS treatment PD. However, the function STN in normal conditions and pathology poorly understood. Here, we show rats that optogenetic modulation neuronal activity exerts bidirectional control function, where inhibition increases movement activation decreases...
Abstract Ventral pallidum (VP) is a key node in the neural circuits controlling relapse to drug seeking but how this role relates different VP cell types and their projections poorly understood. Using male rats, we show forms of alcohol-seeking are assembled from lateral hypothalamus (LH) ventral tegmental area (VTA). First, used RNAScope situ hybridization characterize activity during provoked by renewal (context-induced reinstatement). We found that Gad1 parvalbumin (PV), not vGlut2,...