- Australia
francois windels
The University of Queensland, Australia, Queensland Brain Institute, Department Member
The subthalamic nucleus (STN) which contains glutamatergic neurons (Smith and Parent, 1988) has come under focus in Parkinson’s disease (PD) from recent advances in the understanding of the functional organization of the basal ganglia in... more
The subthalamic nucleus (STN) which contains glutamatergic neurons (Smith and Parent, 1988) has come under focus in Parkinson’s disease (PD) from recent advances in the understanding of the functional organization of the basal ganglia in normal and pathological conditions. Based on this organization, normal movements would depend on an equilibrium between the activity of two output pathways from the neostriatum:
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Research Interests: Neuroscience, Physiology, Chemistry, Neurophysiology, Medicine, and 15 moreCerebral Cortex, Animals, Amygdala, Oscillations, Neurons, Rats, Biological clocks, Action Potentials, C, Neurosciences, Basolateral Amygdala, State dependence, Electroshock, Psychology and Cognitive Sciences, and Medical and Health Sciences
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Research Interests: Neuroscience, Chemistry, Deep Brain Stimulation, Electrochemistry, Immunohistochemistry, and 15 moreMedicine, Animals, Male, Microdialysis, Globus Pallidus, Basal ganglia, Electrodes, Glutamic Acid, Neurochemical, Functional Laterality, High Frequency Stimulation, Cell count, Psychology and Cognitive Sciences, Medical and Health Sciences, and Electric stimulation
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Research Interests: Neuroscience, Cognitive Science, Chemistry, Drug interactions, Immunohistochemistry, and 15 moreMedicine, Nucleus Accumbens, Dopamine, Glutamate receptors, Animals, Male, Amphetamine, Neurons, Iontophoresis, Basal ganglia, Action Potentials, Neurosciences, Presynaptic Modulation, Motor activity, and Dopamine antagonists
Research Interests: Chemistry, Electrophysiology, Deep Brain Stimulation, Dopamine, Glutamate, and 15 moreAnimals, Male, High Performance Liquid Chromatography, Amino Acids, High performance, Frequency Dependence, Globus Pallidus, Basal ganglia, Extracellular Space, Glutamic Acid, Glutamate Receptor, High Frequency Stimulation, Medical and Health Sciences, Medical biochemistry and metabolomics, and Electric stimulation
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Research Interests: Chemistry, Deep Brain Stimulation, Medicine, Dopamine, Glutamate, and 15 moreAnimals, Male, GABA, Clinical Neurology, High Performance Liquid Chromatography, Clinical Sciences, Electrical Stimulation, Microdialysis, Globus Pallidus, Basal ganglia, Glutamic Acid, Neurochemical, Glutamate Receptor, Corpus striatum, and Electric stimulation
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GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF
Research Interests: Chemistry, Medicine, Glutamate, Médecine, Globus Pallidus, and 4 moreRat, Neurologie, Grenoble, and Neurophysiologie
This data represents the free fatty acid (FFA) and phospholipid (PL) response to auditory fear conditioning (AFC) across the rat brain in the presence or absence of a memory blocking agent. Four experimental conditions were used, each... more
This data represents the free fatty acid (FFA) and phospholipid (PL) response to auditory fear conditioning (AFC) across the rat brain in the presence or absence of a memory blocking agent. Four experimental conditions were used, each applied to a cohort of 8 rat: saline injected (control) animals, unpaired AFC stimuli (SU); saline injected animals, paired stimuli (SP); CPP (NMDA antagonist) injected animals, unpaired AFC stimuli (CU); CPP injected animals, paired AFC stimuli (CP). Tissue was collected from 6 brain regions CeA – central amygdala, BLA – basolateral amygdala, PFC – prefrontal coretex, DH – dorsal hippocampus, VH – ventral hippocampus, CB – cerebellum Lipidomics analysis using targeted LCMSMS was performed for FFA – free fatty acid, PA – phosphatidic acid, PC- phosphatidylcholine, PE – phosphatidylcholine, PG – phosphatidylglycerol, PS – phosphatidylserine Data contains the quantified abundance for each targeted lipid species for each of the 4 AFC conditions, 8 animals, 6 brain regions
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Background The globus pallidus internus is the main target for the treatment of dystonia by deep brain stimulation. Unfortunately, for some genetic etiologies, the therapeutic outcome of dystonia is less predictable. In particular,... more
Background The globus pallidus internus is the main target for the treatment of dystonia by deep brain stimulation. Unfortunately, for some genetic etiologies, the therapeutic outcome of dystonia is less predictable. In particular, therapeutic outcomes for deep brain stimulation in craniocervical and orolaryngeal dystonia in DYT6-positive patients are poor. Little is known about the neurophysiology of the globus pallidus internus in DYT6-positive dystonia, and how symptomatic treatment affects the neural activity of this region. Case presentation We present here the case of a 55-year-old Caucasian female DYT6-dystonic patient with blepharospasm, spasmodic dysphonia, and oromandibular dystonia where single-unit and local field potential activity was recorded from the globus pallidus internus during two deep brain stimulation revision surgeries 4 years apart with no symptomatic improvement. Botulinum toxin injections consistently improved dysphonia, while some of the other symptoms we...
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modulates neuronal network dynamics in the human pedunculopontine nucleus. The pedunculopontine nucleus (PPN) is a part of the mesencephalic locomotor region and thought to play a key role in the initiation and maintenance of gait.... more
modulates neuronal network dynamics in the human pedunculopontine nucleus. The pedunculopontine nucleus (PPN) is a part of the mesencephalic locomotor region and thought to play a key role in the initiation and maintenance of gait. Lesions of the PPN induce gait deficits, and the PPN has therefore emerged as a target for deep brain stimulation for the control of gait and postural disability. However, the role of the PPN gait control is not understood. Here, using extracellular single unit recordings in awake patients, we show that neurons in the PPN discharge as synchronous functional networks whose activity is phase locked to alpha oscillations. Neurons within the PPN respond to limb movement and imagined gait by dynamically changing network activity, and decreasing alpha phase locking. These results show that different synchronous networks are activated during initial motor planning and actual motion, and suggest that changes in gait initiation in PD may result from disrupted netw...
1ABSTRACTDeep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ±10.7 years) were implanted with DBS electrodes... more
1ABSTRACTDeep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ±10.7 years) were implanted with DBS electrodes bilaterally in the bed nucleus of the stria terminalis (BNST). Following a one-month postoperative recovery phase, participants entered a three-month randomised, double-blind, sham-controlled phase before a twelve-month period of open-label stimulation incorporating a course of cognitive behavioural therapy (CBT). The primary outcome measure was OCD symptoms as rated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the blinded phase, there was a significant benefit of active stimulation over sham (p = 0.025, mean difference 4.9 points). After the open phase, the mean reduction in YBOCS was 16.6 ±1.9 points (Χ2 (11) = 39.8, p = 3.8 × 10−5), with seven participants classified as responders. CBT resulted in an additive YBOCS reduction of 4.8 ±3.9 ...
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The knowledge of the mechanisms regulating electric neuronal activity is fragmented by the wide variety of techniques and experimental models currently used in neurophysiological research. The interest and importance of the results... more
The knowledge of the mechanisms regulating electric neuronal activity is fragmented by the wide variety of techniques and experimental models currently used in neurophysiological research. The interest and importance of the results obtained in any research is improved when interpreted in the perspective of the organism functioning as a whole in physiological conditions. Such interpretation, freed of the constraints imposed by the different techniques and experimental conditions used, is especially important when discussing together results obtained at the behavioral, cellular, and molecular level. This article outlines some of the key factors to consider when experiments from different models are interpreted together.
Research Interests: Neuroscience, Cognitive Science, Electrophysiology, Biology, Neurophysiology, and 15 moreMedicine, Molecular Neurobiology, In Vitro, Circadian Rhythm, Animals, Nicotinic Acetylcholine Receptors, Anesthesia, Neurons, In Vivo, Anesthetics, Neuronal Activity, Environment, Neurosciences, Experimental Models, and Experimental Model
The partial reinforcement extinction effect (PREE) is a paradoxical learning phenomenon in which omission of reinforcement during acquisition results in more persistent conditioned responding in extinction. Here, we report a significant... more
The partial reinforcement extinction effect (PREE) is a paradoxical learning phenomenon in which omission of reinforcement during acquisition results in more persistent conditioned responding in extinction. Here, we report a significant PREE with an inverted-U, entropy-like distribution against reinforcement probability following tone foot shock fear conditioning in rats, which was associated with increased neural activity in hippocampus and amygdala as indexed by p-ERK and c-fos immunolabelling. In vivo electrophysiological recordings of local field potentials (LFPs) showed that 50% reinforcement was associated with increases in the frequency and power of tone-evoked theta oscillations in both the subiculum region of hippocampus and in basolateral amygdala (BLA) during both acquisition (Day 1) and extinction (Day 2) sessions. Tone-evoked LFPs in 50% reinforced animals also showed increases in coherence and bidirectional Granger Causality between hippocampus and amygdala. The result...
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In quiescent states such as anesthesia and slow wave sleep, cortical networks show slow rhythmic synchronized activity. In sensory cortices this rhythmic activity shows a stereotypical pattern that is recapitulated by stimulation of the... more
In quiescent states such as anesthesia and slow wave sleep, cortical networks show slow rhythmic synchronized activity. In sensory cortices this rhythmic activity shows a stereotypical pattern that is recapitulated by stimulation of the appropriate sensory modality. The amygdala receives sensory input from a variety of sources, and in anesthetized animals, neurons in the basolateral amygdala (BLA) show slow rhythmic synchronized activity. Extracellular field potential recordings show that these oscillations are synchronized with sensory cortex and the thalamus, with both the thalamus and cortex leading the BLA. Using whole-cell recording in vivo we show that the membrane potential of principal neurons spontaneously oscillates between up- and down-states. Footshock and auditory stimulation delivered during down-states evokes an up-state that fully recapitulates those occurring spontaneously. These results suggest that neurons in the BLA receive convergent input from networks of corti...
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The pallido-subthalamic pathway powerfully controls the output of the basal ganglia circuitry and has been implicated in movement disorders observed in Parkinson's disease (PD). To investigate the normal functioning of this pathway across... more
The pallido-subthalamic pathway powerfully controls the output of the basal ganglia circuitry and has been implicated in movement disorders observed in Parkinson's disease (PD). To investigate the normal functioning of this pathway across the sleep–wake cycle, single-unit activities of subthalamic nucleus (STN) and globus pallidus (GP) neurons were examined, together with cortical electroencephalogram and nuchal muscular activity, in non-anaesthetized head-restrained rats. STN neurons shifted from a random discharge in wakefulness (W) to a bursting pattern in slow wave sleep (SWS), without any change in their mean firing rate. This burst discharge occurred in the 1–2 Hz range, but was not correlated with cortical slow wave activity. In contrast, GP neurons, with a mean firing rate higher in W than in SWS, exhibited a relatively regular discharge whatever the state of vigilance. During paradoxical sleep, both STN and GP neurons increased markedly their mean firing rate relative to W and SWS. Our results are not in agreement with the classical ‘direct/indirect’ model of the basal ganglia organization, as an inverse relationship between STN and GP activities is not observed under normal physiological conditions. Actually, because the STN discharge pattern appears dependent on coincident cortical activity, this nucleus can hardly be viewed as a relay along the indirect pathway, but might rather be considered as an input stage conveying corticothalamic information to the basal ganglia.
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The role of the p75 neurotrophin receptor (p75(NTR)) in adult cholinergic basal forebrain (cBF) neurons is unclear due to conflicting results from previous studies and to limitations of existing p75(NTR)-knock-out mouse models. In the... more
The role of the p75 neurotrophin receptor (p75(NTR)) in adult cholinergic basal forebrain (cBF) neurons is unclear due to conflicting results from previous studies and to limitations of existing p75(NTR)-knock-out mouse models. In the present study we used a novel conditional knock-out line (ChAT-cre p75(in/in)) to assess the role of p75(NTR) in the cBF by eliminating p75(NTR) in choline acetyl-transferase-expressing cells. We show that the absence of p75(NTR) results in a lasting increase in cBF cell number, cell size, and cholinergic innervation to the cortex. Analysis of adult ChAT-cre p75(in/in) mice revealed that mutant animals show a similar loss of cBF neurons with age to that observed in wild-type animals, indicating that p75(NTR) does not play a significant role in mediating this age-related decline in cBF neuronal number. However, the increased cholinergic axonal innervation of the cortex, but not the hippocampus, corresponded to alterations in idiothetic but not allotheti...
Research Interests: Neuroscience, Cognition, Mice, Female, Animals, and 3 moreMale, Synaptic Transmission, and Maze Learning
The knowledge of the mechanisms regulating electric neuronal activity is fragmented by the wide variety of techniques and experimental models currently used in neurophysiological research. The interest and importance of the results... more
The knowledge of the mechanisms regulating electric neuronal activity is fragmented by the wide variety of techniques and experimental models currently used in neurophysiological research. The interest and importance of the results obtained in any research is improved when interpreted in the perspective of the organism functioning as a whole in physiological conditions. Such interpretation, freed of the constraints imposed by the different techniques and experimental conditions used, is especially important when discussing together results obtained at the behavioral, cellular, and molecular level. This article outlines some of the key factors to consider when experiments from different models are interpreted together.
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It is hypothesized that substantia nigra pars reticulata neurons become overactive during a deficit of dopamine transmission. In this study, we examined how acute dopamine receptor blockade (SCH23390 and eticlopride) affects impulse... more
It is hypothesized that substantia nigra pars reticulata neurons become overactive during a deficit of dopamine transmission. In this study, we examined how acute dopamine receptor blockade (SCH23390 and eticlopride) affects impulse activity of substantia nigra pars reticulata neurons and their response to iontophoretic gamma-amino-n-butyric acid in awake, unrestrained rats. No changes in discharge rate were found during complete dopamine receptor blockade, but these neurons showed a diminished response to gamma-amino-n-butyric acid, suggesting gamma-amino-n-butyric acid receptor hyposensitivity. This may result from tonic increase in gamma-amino-n-butyric acid input from the striatum and globus pallidus, which are activated during dopamine receptor blockade. As substantia nigra pars reticulata neurons are autoactive and resistant to tonic increases in gamma-amino-n-butyric acid input, changes in their responsiveness to phasic gamma-amino-n-butyric acid inputs, not tonic increase di...
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Although it is evident that general anesthesia should affect impulse activity and neurochemical responses of central neurons, there are limited studies in which these parameters were compared in both awake and anesthetized animal... more
Although it is evident that general anesthesia should affect impulse activity and neurochemical responses of central neurons, there are limited studies in which these parameters were compared in both awake and anesthetized animal preparations. We used single-unit recording coupled with iontophoresis to examine impulse activity and responses of substantia nigra pars reticulata (SNr) neurons to GABA, glutamate (GLU), and dopamine (DA) in rats in awake, unrestrained conditions and during chloral hydrate anesthesia. SNr neurons in both conditions had similar organization of impulse flow, but during anesthesia, they have lower mean rates and discharge variability than in awake conditions. In individual units, discharge rate in awake, quietly resting rats was almost three-fold more variable than during anesthesia. These cells in both conditions were highly sensitive to iontophoretic GABA, but the response was stronger during anesthesia. In contrast to virtually no responses to GLU in awak...
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High-frequency stimulation of the subthalamic nucleus (HFS-STN) is an effective treatment for alleviating the motor symptoms of parkinsonian patients. However, the neurochemical basis of its effects remains unknown. We showed previously... more
High-frequency stimulation of the subthalamic nucleus (HFS-STN) is an effective treatment for alleviating the motor symptoms of parkinsonian patients. However, the neurochemical basis of its effects remains unknown. We showed previously that 1 h of HFS-STN in normal rats increases extracellular glutamate (Glu) level in the output nuclei of the STN, the globus pallidus (GP), and the substantia nigra pars reticulata (SNr), consistent with an increase in the activity of STN neurons. HFS-STN also increases GABA levels in the SNr, but the origin of this increase is unclear. We investigated the effectiveness of HFS-STN for improving Parkinson's disease symptoms, using intracerebral microdialysis to determine the extracellular Glu and GABA levels of the GP and SNr in response to HFS-STN in anesthetized hemiparkinsonian rats [6-hydroxydopamine lesion of the substantia nigra pars compacta (SNc)]. Basal levels of Glu and GABA in the GP and SNr were significantly higher in hemiparkinsonian...
Research Interests: Neuroscience, Electrochemistry, Immunohistochemistry, Subthalamic Nucleus, Glutamate, and 14 moreAnimals, Male, Substantia nigra, The, High Pressure Liquid Chromatography, Microdialysis, Rats, Globus Pallidus, Electrodes, Somatic Cell Count, Neurosciences, Glutamic Acid, Gamma-Aminobutyric Acid, and Functional Laterality
Substantia nigra pars reticulata (SNr) receives both GABAergic and glutamatergic (GLU) inputs that are believed to act together to regulate neuronal activity in this structure. To examine the role of these inputs, single-unit recording... more
Substantia nigra pars reticulata (SNr) receives both GABAergic and glutamatergic (GLU) inputs that are believed to act together to regulate neuronal activity in this structure. To examine the role of these inputs, single-unit recording was coupled with iontophoresis of GLU and GABA in rats under two conditions: awake, unrestrained and under chloral hydrate anesthesia. Although GABA potently inhibited SNr cells in both conditions, freely moving rats showed lower sensitivity than anesthetized animals. Likewise, GLU effectively induced excitations in most SNr neurons in anesthetized animals but was much less effective in awake, unrestrained animals in terms of both the number of sensitive cells and the magnitude of GLU-induced excitation. These findings, along with consistent excitations induced by bicuculline in awake, unrestrained rats, suggest that modulation of GABA inhibitory input, not the opposing actions of GLU and GABA, is the primary factor that regulates the activity state o...
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High frequency stimulation (HFS) (130 Hz) of the subthalamic nucleus (STN) provides beneficial effects in patients suffering from severe parkinsonism, but the mechanisms underlying these clinical results remain to be clarified. To date,... more
High frequency stimulation (HFS) (130 Hz) of the subthalamic nucleus (STN) provides beneficial effects in patients suffering from severe parkinsonism, but the mechanisms underlying these clinical results remain to be clarified. To date, very little is known concerning the effects of STN-HFS on neurochemical transmission in the different basal ganglia nuclei and in particular the striatum. This study examines the effects of STN-HFS in intact and hemiparkinsonian rats on extracellular striatal glutamate (Glu) and GABA levels by means of intracerebral microdialysis. Unilateral STN-HFS was found to induce a significant bilateral increase of striatal Glu and GABA both in intact and in dopamine-lesioned animals. In intact rats, these increases were reversed by local administration of the D1 antagonist SCH 23390, but were potentiated by the D2 antagonist sulpiride. Potentiation was also observed after local administration of both D1 and D2 antagonists whose amplitude was similar to that me...
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The subthalamic nucleus (STN) which contains glutamatergic neurons (Smith and Parent, 1988) has come under focus in Parkinson’s disease (PD) from recent advances in the understanding of the functional organization of the basal ganglia in... more
The subthalamic nucleus (STN) which contains glutamatergic neurons (Smith and Parent, 1988) has come under focus in Parkinson’s disease (PD) from recent advances in the understanding of the functional organization of the basal ganglia in normal and pathological conditions. Based on this organization, normal movements would depend on an equilibrium between the activity of two output pathways from the neostriatum: