Cognition, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Mammalia, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Animal, Cervelet, Cerebellum, Cerebelo, Cortex cérébral, Cerebral cortex, Corteza cerebral, Encéphale, Encephalon, Encéfalo, Faisceau septohippocampique, Septohippocampal bundle, Haz septohipocámpico, Moelle épinière, Spinal cord, Médula espinal, Neurone moteur, Motor neuron, Neurona motora, Prosencéphale, Prosencephalon, Prosencéfalo, Souris, Mouse, Ratón, basal forebrain, cerebellum, cerebral cortex, mouse, septohippocampal neurons, and somatic motor neurons

Components of the Reelin-signaling pathway are highly expressed in embryos and regulate neuronal positioning, whereas these molecules are expressed at low levels in adults and modulate synaptic plasticity. Reelin binds to Apolipoprotein E receptor 2 and Very-low-density lipoprotein receptors, triggers the phosphorylation of Disabled-1 (Dab1), and initiates downstream signaling. The expression of Dab1 marks neurons that potentially respond to Reelin, yet phosphorylated Dab1 is difficult to detect due to its rapid ubiquitination and degradation. Here we used adult mice with a lacZ gene inserted into the dab1 locus to first verify the coexpression of β-galactosidase (β-gal) in established Dab1-immunoreactive neurons and then identify novel Dab1-expressing neurons. Both cerebellar Purkinje cells and spinal sympathetic preganglionic neurons have coincident Dab1 protein and β-gal expression in dab1lacZ/+ mice. Adult pyramidal neurons in cortical layers II-III and V are labeled with Dab1 and/or β-gal and are inverted in the dab1lacZ/lacZ neocortex, but not in the somatosensory barrel fields. Novel Dab1 expression was identified in GABAergic medial septum/diagonal band projection neurons, cerebellar Golgi interneurons, and small neurons in the deep cerebellar nuclei. Adult somatic motor neurons also express Dab1 and show ventromedial positioning errors in dab1-null mice. These findings suggest that: (i) Reelin regulates the somatosensory barrel cortex differently than other neocortical areas, (ii) most Dab1 medial septum/diagonal band neurons are probably GABAergic projection neurons, and (iii) positioning errors in adult mutant Dab1-labeled neurons vary from subtle to extensive.

Cognition, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Neurone et nerf isolés. Névroglie, Isolated neuron and nerve. Neuroglia, Sciences medicales, Medical sciences, Neurologie, Neurology, Système nerveux (sémiologie, syndromes), Nervous system (semeiology, syndromes), Syndromes encéphaliques généraux: céphalées, douleurs de la face, syncopes, épilepsie, hypertension intracrânienne, oedème cérébral. Infirmité motrice cérébrale, Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy, Encéphale, Encephalon, Encéfalo, Mammalia, Pathologie de l'encéphale, Cerebral disorder, Encéfalo patología, Pathologie du système nerveux central, Central nervous system disease, Sistema nervosio central patología, Pathologie du système nerveux, Nervous system diseases, Sistema nervioso patología, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Epilepsie, Epilepsy, Epilepsia, Excitabilité, Excitability, Excitabilidad, Hippocampe, Hippocampus, Hipocampo, Long terme, Long term, Largo plazo, Métabolisme, Metabolism, Metabolismo, Neurone, Neuron, Neurona, Souris, Mouse, Ratón, Excitability of neurons, and Homocysteine

Homocystinuria is an inborn error of metabolism characterized by plasma homocysteine levels up to 500 μM, premature vascular events and mental retardation. Mild elevations of homocysteine plasma levels up to 25 μM, which are common in the general population, are associated with vascular disease, cognitive impairment and neurodegeneration. Several mechanisms of homocysteine neurotoxicity have been investigated. However, information on putative effects of hyperhomocysteinemia on the electrophysiology of neurons is limited. To screen for such effects, we examined primary cultures of mouse hippocampal neurons with the whole-cell patch-clamp technique. Homocysteine was applied intracellularly (100 μM), or cell cultures were incubated with 100 μM homocysteine for 24 h. Membrane voltage was measured in current-clamp mode, and action potential firing was induced with short and prolonged current injections. Single action potentials induced by short current injections (5 ms) were not altered by acute application or incubation of homocysteine. When we elicited trains of action potentials with prolonged current injections (200 ms), a broadening of action potentials during repetitive firing was observed in control neurons. This spike broadening was unaltered by acute application of homocysteine. However, it was significantly diminished when incubation with homocysteine was extended to 24 h prior to recording. Furthermore, the number of action potentials elicited by low current injections was reduced after long-term incubation with homocysteine, but not by the acute application. After 24 h of homocysteine incubation, the input resistance was reduced which might have contributed to the observed alterations in membrane excitability. We conclude that homocysteine exposure causes changes in the intrinsic electrophysiological properties of cultured hippocampal neurons as a mechanism of neurological symptoms of hyperhomocysteinemia.

Encéphale, Encephalon, Encéfalo, Mammalia, Noyau gris central, Basal ganglion, Núcleo basal, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Adaptation, Adaptación, Animal, Autoadministration, Self administration, Autoadministración, Corps strié, Corpus striatum, Cuerpo estriado, Electrophysiologie, Electrophysiology, Electrofisiología, Neurone, Neuron, Neurona, Opiacés, Opiates, Opiados, Peptide opioïde, Opioid peptide, Péptido opioide, Récepteur opiacé μ, μ Opioid receptor, Receptor opiáceo μ, Souris, Mouse, Ratón, Voie intraveineuse, Intravenous administration, Vía intravenosa, Intravenous self-administration, Medium spiny neurons, Mice, Mu opioid receptor, Striatum, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Psychologie. Psychophysiologie, Psychology. Psychophysiology, Psychophysiologie du comportement, Behavioral psychophysiology, Psychologie. Psychanalyse. Psychiatrie, Psychology. Psychoanalysis. Psychiatry, Cognition, Psychophysiology, and Psychophysiologie

Medium-sized spiny neurons (MSNs), the predominant neuronal population of the striatum, are an integral component of the many cortical and limbic pathways associated with reward-related behaviors. A differential role of the D1 receptor-enriched (D1) MSNs of the striatonigral direct pathway, as compared with the D2 receptor-enriched (D2) MSNs of the striatopallidal indirect pathway, in mediating the addictive behaviors associated with cocaine is beginning to emerge. However, whether opioids, well-known analgesics with euphoric properties, similarly induce dissociable signaling adaptations in these neurons remains unclear. Transgenic mice expressing green fluorescent protein (GFP)-labeled D1 or D2 neurons were implanted with intravenous jugular catheters. Mice learned to self-administer 0.1 mg/kg/infusion of the opioid remifentanil during 2 h sessions over 13 contiguous days. Thereafter, the electrophysiological properties of D1- and D2-MSNs in the shell region of the nucleus accumbens (NAc) were assessed. We found that prior opioid exposure did not alter the basic membrane properties nor the kinetics or amplitude of miniature excitatory postsynaptic currents (mEPSCs). However, when challenged with the mu opioid receptor (μOR) agonist DAMGO, the characteristic inhibitory profile of this receptor was altered. DAMGO inhibited the frequency of mEPSCs in D1-MSNs from control mice receiving saline and in D2-MSNs from mice exposed to remifentanil or saline, but this inhibitory profile was reduced in D1-MSNs from mice receiving remifentanil. Remifentanil exposure also altered the probability of glutamate release onto D1-, but not D2-MSNs. Together these results suggest a D1-pathway specific effect associated with the acquisition of opioid-seeking behaviors.

Cognition, Psychophysiology, Psychophysiologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Psychologie. Psychophysiologie, Psychology. Psychophysiology, Psychophysiologie du comportement, Behavioral psychophysiology, Psychologie. Psychanalyse. Psychiatrie, Psychology. Psychoanalysis. Psychiatry, Encéphale, Encephalon, Encéfalo, Mammalia, Noyau gris central, Basal ganglion, Núcleo basal, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Adaptation, Adaptación, Animal, Autoadministration, Self administration, Autoadministración, Corps strié, Corpus striatum, Cuerpo estriado, Electrophysiologie, Electrophysiology, Electrofisiología, Neurone, Neuron, Neurona, Opiacés, Opiates, Opiados, Peptide opioïde, Opioid peptide, Péptido opioide, Récepteur opiacé μ, μ Opioid receptor, Receptor opiáceo μ, Souris, Mouse, Ratón, Voie intraveineuse, Intravenous administration, Vía intravenosa, Intravenous self-administration, Medium spiny neurons, Mice, Mu opioid receptor, and Striatum

Medium-sized spiny neurons (MSNs), the predominant neuronal population of the striatum, are an integral component of the many cortical and limbic pathways associated with reward-related behaviors. A differential role of the D1 receptor-enriched (D1) MSNs of the striatonigral direct pathway, as compared with the D2 receptor-enriched (D2) MSNs of the striatopallidal indirect pathway, in mediating the addictive behaviors associated with cocaine is beginning to emerge. However, whether opioids, well-known analgesics with euphoric properties, similarly induce dissociable signaling adaptations in these neurons remains unclear. Transgenic mice expressing green fluorescent protein (GFP)-labeled D1 or D2 neurons were implanted with intravenous jugular catheters. Mice learned to self-administer 0.1 mg/kg/infusion of the opioid remifentanil during 2 h sessions over 13 contiguous days. Thereafter, the electrophysiological properties of D1- and D2-MSNs in the shell region of the nucleus accumbens (NAc) were assessed. We found that prior opioid exposure did not alter the basic membrane properties nor the kinetics or amplitude of miniature excitatory postsynaptic currents (mEPSCs). However, when challenged with the mu opioid receptor (μOR) agonist DAMGO, the characteristic inhibitory profile of this receptor was altered. DAMGO inhibited the frequency of mEPSCs in D1-MSNs from control mice receiving saline and in D2-MSNs from mice exposed to remifentanil or saline, but this inhibitory profile was reduced in D1-MSNs from mice receiving remifentanil. Remifentanil exposure also altered the probability of glutamate release onto D1-, but not D2-MSNs. Together these results suggest a D1-pathway specific effect associated with the acquisition of opioid-seeking behaviors.

Cognition, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Système nerveux central, Central nervous system, Biochimie et métabolisme, Biochemistry and metabolism, Adipokine, Adipoquina, Encéphale, Encephalon, Encéfalo, Mammalia, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Acétylation, Acetylation, Acetilación, Animal, Chromatine, Chromatin, Cromatina, DNA, Décitabine, Decitabine, Decitabina, Expression génique, Gene expression, Expresión genética, Histone, Histona, Hypothalamus, Hipotálamo, Leptine, Leptin, Leptina, Méthylation, Methylation, Metilación, Neurone, Neuron, Neurona, Souris, Mouse, Ratón, 5-aza-2'-deoxycytidine, DNA methylation, chromatin, cycloheximide, histone acetylation, hypothalamic neurons, and leptin, trichostatin A

In marked contrast to several other species, including rats and humans, leptin gene expression is undetectable in mouse brain. This unexpected finding may reflect unique energy regulation pathways in the mouse. We investigated possible mechanisms by which leptin (ob) gene expression is suppressed in mouse brain: (a) the possibility that ob mRNA levels might be detectable in vitro through the superinduction of gene expression following protein synthesis inhibition and (b) whether chromatin modification of the ob gene was responsible for this repression. Experiments were conducted on mouse hypothalamic neurons in vitro. Cells were treated with (a) protein synthesis inhibitors: cycloheximide (CHX; 25 μg/ml); puromycin (50 μg/ml); anisomycin (5 μM); (b) trichostatin A (histone deacetylase inhibitor; 500 nM); and (c) 5-aza-2'-deoxycytidine (DNA methylation inhibitor; 5 μM). Following the incubations, cells were harvested for the preparation of RNA and ob mRNA was detected using real-time reverse transcription PCR. Protein synthesis inhibitors induced a rapid increase in ob mRNA levels in mouse hypothalamic neurons in vitro. For example CHX stimulation of ob mRNA was detectable at 60 min after treatment and reached a maximum between 4 and 6 h. A dose-response analysis, with concentrations of CHX of 1, 2, 10, 25, and 50 μg/ml, indicated that CHX was already effective at 1.0 μg/ml, with a maximal effect by 25 μg/ml. In contrast, incubation with trichostatin A and 5-aza-2'-deoxycytidine had no effect and ob mRNA remained undetectable. These data show that leptin gene expression is superinduced in ob-negative mouse hypothalamic neurons following inhibition of protein synthesis. They confirm that the previously reported absence of leptin mRNA in mouse brain is probably because of an active repressive mechanism, although this may not involve chromatin modification.

Cognition, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Encéphale, Encephalon, Encéfalo, Mammalia, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Animal, Distribution, Distribución, Hippocampe, Hippocampus, Hipocampo, Immunohistochimie, Immunohistochemistry, Inmunohistoquímica, Neurone gabaergique, Gabaergic neuron, Neurona gabaminérgica, Protéine G, G protein, Proteína G, Récepteur biologique, Biological receptor, Receptor biológico, Récepteur opiacé δ, δ Opioid receptor, Receptor opiáceo δ, Souris, Mouse, Ratón, G protein-coupled receptor, GABAergic neurons, fluorescent knock-in mouse, and immunohistochemistry

Delta opioid receptors participate to the control of chronic pain and emotional responses. Recent data also identified their implication in spatial memory and drug-context associations pointing to a critical role of hippocampal delta receptors. We examined the distribution of delta receptor-expressing cells in the hippocampus using fluorescent knock-in mice that express a functional delta receptor fused at its carboxyterminus with the green fluorescent protein in place of the native receptor. Colocalization with markers for different neuronal populations was performed by immunohistochemical detection. Fine mapping in the dorsal hippocampus confirmed that delta opioid receptors are mainly present in GABAergic neurons. Indeed, they are mostly expressed in parvalbumin-immunopositive neurons both in the Ammon's horn and dentate gyrus. These receptors, therefore, most likely participate in the dynamic regulation of hippocampal activity.

Cell biology, histology, Biologie cellulaire, histologie, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Biologie moleculaire et cellulaire, Molecular and cellular biology, Structures cellulaires et fonctions, Cell structures and functions, Récepteurs cellulaires, Cell receptors, Récepteurs monoamines (catécholamine, sérotonine, histamine, acétylcholine), Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine), Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Système nerveux central, Central nervous system, Neurotransmission centrale. Neuromodulation. Voies et récepteurs, Central neurotransmission. Neuromudulation. Pathways and receptors, Enzyme, Enzima, Mammalia, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Transferases, Vertebrata, Antagoniste, Antagonist, Antagonista, Cortex cérébral, Cerebral cortex, Corteza cerebral, Culture primaire, Primary culture, Cultivo primario, Encéphale, Encephalon, Encéfalo, Neurone, Neuron, Neurona, Non-specific serine/threonine protein kinase, Phosphorylation, Fosforilación, Protéine, Protein, Proteína, Récepteur dopaminergique D1, D1 Dopamine receptor, Receptor dopaminérgico D1, Récepteur dopaminergique, Dopamine receptor, Receptor dopaminérgico, Récepteur ryanodine, Ryanodine receptor, Receptor ryanodina, Souris, Mouse, Ratón, Transduction signal, Signal transduction, Transducción señal, CREB, cerebral cortical neurons in primary culture, dopamine D1 receptors, methamphetamine, protein kinase A, and ryanodine receptors

Regulatory mechanisms of ryanodine receptor (RyR) expression are not well known, although methamphetamine (METH) has been reported to up-regulate RyRs in mouse brain. This study investigate regulatory mechanisms of RyR expression by dopaminergic system using the midbrain and cerebral cortical neurons in primary culture intermittently exposed to METH and dopamine receptor (DR) agonists (1 h/day, for 3 days). Intermittent METH (10 μM) exposure enhanced RyR-1 and -2 proteins and their mRNA, but not RyR-3 expression in the both types of the neurons. These METH-induced increases of RyR proteins and their mRNA were dose-dependently blocked by SCH23390 (a selective D1DR antagonist), but not a D2DR antagonist sulpiride, suggesting a regulatory role of D1DRs in RyR expression by METH in these neurons. In cerebral cortical neurons, intermittent SKF82958 (a selective D1DR agonist) exposure increased RyR-1 and -2 proteins and their mRNA, whereas quinpirole (a selective D2DR agonist) showed no effects. KT5720, a protein kinase A inhibitor, dose-dependently attenuated the METH-stimulated RyR-1 and -2 expressions in cerebral cortical neurons. METH significantly increased phosphorylation of cAMP-response element-binding protein, which was completely suppressed by SCH23390. These results indicate that RyR-1 and -2 expressions are regulated by D1Rs via the signal transduction linked to D1DRs.

Cognition, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Système nerveux central, Central nervous system, Neurotransmission centrale. Neuromodulation. Voies et récepteurs, Central neurotransmission. Neuromudulation. Pathways and receptors, Somesthésie et voies somesthésiques (proprioception, extéroception, nociception); intéroception; électrolocation. Récepteurs sensoriels, Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors, Encéphale, Encephalon, Encéfalo, Mammalia, Rodentia, Récepteur glutamate, Glutamate receptor, Receptor glutámato, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Voie somesthésique, Somesthetic pathway, Vía somestésica, Calcium, Calcio, Composition, Composicion, Cortex cérébral, Cerebral cortex, Corteza cerebral, Cortex somatosensoriel, Somatosensory cortex, Corteza somatosensorial, Couplage, Coupling, Acoplamiento, Facilitation, Facilitación, Hippocampe, Hippocampus, Hipocampo, Libération, Release, Liberación, Neurone glutamatergique, Glutamatergic neuron, Neurona glutamatérgica, Neurone pyramidal, Pyramidal neuron, Neurona piramidal, Récepteur NMDA, NMDA receptor, Receptor NMDA, Souris, Mouse, Ratón, Sousunité NR2A, Sousunité NR2B, Glutamatergic synapses, NMDA receptors, Pyramidal neurons, Subunit composition, and Vesicle release

Following initial contact formation, glutamatergic synapses in cortical neurons undergo pronounced functional maturation. These maturational events, occurring both pre- and postsynaptically, have been well described in the developing hippocampus. In this paper, we characterized glutamatergic synapses in immature layer Vb pyramidal neurons of the mouse somatosensory cortex during early postnatal development. At postnatal day 7, a significant subpopulation of glutamatergic synapses exhibited a low release probability that was accompanied by strong paired-pulse facilitation of AMPA EPSCs (paired-pulse ratio > 2). Increasing extracellular Ca2+ concentration increased release probability and led to paired-pulse depression. During further postnatal development, these functionally immature synapses disappeared. As shown pharmacologically, these synapses expressed postsynaptic NMDA receptors containing NR2B subunits, while NMDA receptors with NR2A subunits were lacking. Taken together, a low release probability presynaptically was coupled to postsynaptic NR2B signaling. This subpopulation of neocortical synapses thus differed from the majority of synapses in the developing hippocampus, where high release probability is coupled to NR2B signaling. The novel type of functionally immature glutamatergic synapse described here might play an important role in early developmental synapse elimination and in the activity-dependent refinement of the neocortical synaptic microcircuitry.

Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Aminoacide excitateur, Excitatory aminoacid, Aminoácido excitador, Encéphale, Encephalon, Encéfalo, Mammalia, Neurotransmetteur, Neurotransmitter, Neurotransmisor, Névroglie, Neuroglia, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Animal, Astrocyte, Astrocito, Cortex cérébral, Cerebral cortex, Corteza cerebral, Glutamate, Glutamato, Neurone, Neuron, Neurona, Protéine transport, Carrier protein, Proteína transportador, Souris, Mouse, Ratón, Astrocytes, EAAT4, Glutamate transporters, Neocortex, and Neurons

EAAT4-eGFP BAC reporter transgenic adult mice were used to detect EAAT4 gene expression in individual cells of cerebral cortex, and eGFP fluorescence was measured to compare EAAT4 promoter activity in different cells. Most eGFP+ cells were neurons; only rare GFAP+ profiles were eGFP+. About 10% ofNeuN+ cells was eGFP+, and the percentage of NeuN/eGFP co-localization varied from 2 to 20% of NeuN+ cells throughout cortical layers: layers I and II-III showed the highest values of co-localization, layer IV the lowest. The intensity of eGFP fluorescence did not exhibit laminar variations. Finally, we observed that EAAT4 promoter activity in cortical neurons was 10% of that measured in cerebellar Purkinje cells, i.e., the cells displaying the highest intensity in the CNS. These results extend our knowledge on EAAT4 expression in the cerebral cortex of adult mice, and suggest that the role of EAAT4 in cortical glutamatergic transmission may be more important than previously thought.

Biomedical engineering, Génie biomédical, Otorhinolaryngology, stomatology, dentistry, Otorhinolaryngologie, stomatologie, dentisterie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Somesthésie et voies somesthésiques (proprioception, extéroception, nociception); intéroception; électrolocation. Récepteurs sensoriels, Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors, Encéphale, Encephalon, Encéfalo, Mammalia, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Animal, Dent, Tooth, Diente, Denture, Teeth, Dentado, Expression génique, Gene expression, Expresión genética, Gène fos, fos Gene, Gen fos, Neurone gabaergique, Gabaergic neuron, Neurona gabaminérgica, Nociception, Nocicepción, Noyau trijumeau, Trigeminal nucleus, Núcleo trigeminal, Pulpe dentaire, Dental pulp, Pulpa dental, Souris, Mouse, Ratón, Stimulus électrique, Electrical stimulus, Estímulo eléctrico, Fos, GABAergic neurons, nociception, spinal trigeminal nucleus, and tooth pulp stimulation

The functional impact of GABA (γ-aminobutyric acid)ergic neurons in nociceptive transmission of the spinal trigeminal nucleus is not fully established. Using both the glutamic acid decarboxylase (GAD)67-green fluorescence protein (GFP) knock-in mouse and the tooth pulp stimulation model, we performed double-immunofluorescent histochemistry to determine the characteristics of GABAergic neuron activation in the spinal trigeminal nucleus. The number of Fos-positive GABAergic neuronal profiles was significantly increased 2 hrs after tooth pulp stimulation. The Fos/GFP double-labeled neurons were mainly present in superficial laminae of the spinal trigeminal subnucleus interpolariscaudalis transition (Vi/Vc) and subnucleus caudalis (Vc) on the side ipsilateral to the stimulation. Subsequently, the number of double-labeled neurons decreased gradually and became comparable with that of the controls by 48 hrs. Our results provide direct morphological evidence that a subset of GABAergic neurons in the spinal trigeminal system was activated during tooth pulp stimulation.

Cognition, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Encéphale, Encephalon, Encéfalo, Mammalia, Neuropeptide, Neuropéptido, Neurotransmetteur, Neurotransmitter, Neurotransmisor, Peptide opioïde, Opioid peptide, Péptido opioide, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Aire tegmentaire ventrale, Ventral tegmental area, Area tegmental ventral, Animal, Enképhaline, Enkephalin, Encefalina, GABA, Immunohistochimie, Immunohistochemistry, Inmunohistoquímica, Neurone dopaminergique, Dopaminergic neuron, Neurona dopaminérgica, Neurone gabaergique, Gabaergic neuron, Neurona gabaminérgica, Noyau du lit de la strie terminale, Bed nucleus of the stria terminalis, Núcleo estría terminal, Souris, Mouse, Ratón, GABAergic neuron, bed nucleus of the stria terminalis, dopaminergic neuron, immunohistochemistry, mouse, and ventral tegmental area

Activation of mu-opioid receptor (MOR) disinhibits dopaminergic neurons in the ventral tegmental area (VTA) through inhibition of γ-aminobutyric acid (GABA)ergic neurons. This mechanism is thought to play a pivotal role in mediating reward behaviors. Here, we characterised VTA-projecting enkephalinergic neurons in the anterior division of the bed nucleus of the stria terminalis (BST) and investigated their targets by examining MOR expression in the VTA. In the BST, neurons expressing preproenkephalin mRNA were exclusively GABAergic, and constituted 37.2% of the total GABAergic neurons. Using retrograde tracer injected into the VTA, 21.6% of VTA-projecting BST neurons were shown to express preproenkephalin mRNA. Enkephalinergic projections from the BST exclusively formed symmetrical synapses onto the dendrites of VTA neurons. In the VTA, 74.1% of MOR mRNA-expressing neurons were GABAergic, with the rest being glutamatergic neurons expressing type-2 vesicular glutamate transporter mRNA. However, MOR mRNA was below the detection threshold in dopaminergic neurons. By immunohistochemistry, MOR was highly expressed on the extrasynaptic membranes of dendrites in GABAergic VTA neurons, including dendrites innervated by BST―VTA projection terminals. MOR was also expressed weakly on GABAergic and glutamatergic terminals in the VTA. Given that GABAAα1 is expressed at GABAergic BST―VTA synapses on dendrites of GABAergic neurons [T. Kudo et al. (2012) J. Neurosci., 32, 18035-18046], our results collectively indicate that the BST sends dual inhibitory outputs targeting GABAergic VTA neurons; GABAergic inhibition via 'wired' transmission, and enkephalinergic inhibition via 'volume' transmission. This dual inhibitory system provides the neural substrate underlying the potent disinhibitory control over dopaminergic VTA neurons exerted by the BST.

Cognition, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Sommeil. Vigilance, Sleep. Vigilance, Electrophysiologie, Electrophysiology, Electrofisiología, Encéphale, Encephalon, Encéfalo, Mammalia, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Agoniste, Agonist, Agonista, Animal, Carbachol, Carbacol, Méthode patch clamp, Patch clamp method, Método patch clamp, Neurone sérotoninergique, Serotoninergic neuron, Neurona serotoninérgica, Sommeil, Sleep, Sueño, Souris, Mouse, Ratón, Substance grise périaqueducale, Periaqueductal gray matter, Substancia gris periacueductal, GAD67-GFP knock-in mice, patch-clamp, presynaptic modulation, sleep, and ventrolateral periaqueductal gray

Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons play an important role in feeding, mood control and stress responses. One important feature of their activity across the sleep-wake cycle is their reduced firing during rapid-eye-movement (REM) sleep which stands in stark contrast to the wake/REM-on discharge pattern of brainstem cholinergic neurons. A prominent model of REM sleep control posits a reciprocal interaction between these cell groups. 5-HT inhibits cholinergic neurons, and activation of nicotinic receptors can excite DRN 5-HT neurons but the cholinergic effect on inhibitory inputs is incompletely understood. Here, in vitro, in DRN brain slices prepared from GAD67-GFP knock-in mice, a brief (3 min) bath application of carbachol (50 μM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in GFP-negative, putative 5-HT neurons but did not affect miniature (tetrodotoxin-insensitive) IPSCs. Carbachol had no direct postsynaptic effect. Thus, carbachol likely increases the activity of local GABAergic neurons which synapse on 5-HT neurons. Removal of dorsal regions of the slice including the ventrolateral periaqueductal gray (vIPAG) region where GABAergic neurons projecting to the DRN have been identified, abolished the effect of carbachol on sIPSCs whereas the removal of ventral regions containing the oral region of the pontine reticular nucleus (PnO) did not. In addition, carbachol directly excited GFP-positive, GABAergic vIPAG neurons. Antagonism of both muscarinic and nicotinic receptors completely abolished the effects of carbachol. We suggest cholinergic neurons inhibit DRN 5-HT neurons when acetylcholine levels are lower i.e. during quiet wakefulness and the beginning of REM sleep periods, in part via excitation of muscarinic and nicotinic receptors located on local vIPAG and DRN GABAergic neurons. Higher firing rates or burst firing of cholinergic neurons associated with attentive wakefulness or phasic REM sleep periods leads to excitation of 5-HT neurons via the activation of nicotinic receptors located postsynaptically and pre-synaptically on excitatory afferents.

Cognition, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Sommeil. Vigilance, Sleep. Vigilance, Encéphale, Encephalon, Encéfalo, Hypothalamus, Hipotálamo, Mammalia, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Animal, Cycle veille sommeil, Sleep wake cycle, Ciclo sueño vigilia, Neurone, Neuron, Neurona, Noyau suprachiasmatique, Suprachiasmatic nucleus, Nucleo supraquiasmático, Souris, Mouse, Ratón, functional heterogeneity, single unit recording, subparaventricular zone, suprachiasmatic nucleus, topographic organization, and wake/sleep cycle

The suprachiasmatic nucleus (SCN) of the mammalian hypothalamus contains a circadian clock for timing of diverse neuronal, endocrine, and behavioral rhythms, such as the cycle of sleep and wakefulness. Using extracellular single unit recordings, we have determined, for the first time, the discharge activity of individual SCN neurons during the complete wake―sleep cycle in non-anesthetized, head restrained mice. SCN neurons (n = 79) were divided into three types according to their regular (type I; n = 38) or irregular (type II; n = 19) discharge activity throughout the wake―sleep cycle or their quiescent activity during waking and irregular discharge activity during sleep (type III; n = 22). The type I and II neurons displayed a long-duration action potential, while the type III neurons displayed either a short-duration or long-duration action potential. The type I neurons discharged exclusively as single isolated spikes, whereas the type II and III neurons fired as single isolated spikes, clusters, or bursts. The type I and II neurons showed wake-active, wake/paradoxical (or rapid eye movement) sleep-active, or state-unrelated activity profiles and were, respectively, mainly located in the ventral or dorsal region of the SCN. In contrast, the type III neurons displayed sleep-active discharge profiles and were mainly located in the lateral region of the SCN. The majority of type I and II neurons tested showed an increase in discharge rate following application of light to the animal's eyes. Of the 289 extra-SCN neurons recorded, those displaying sleep-active discharge profiles were mainly located dorsal to the SCN, whereas those displaying wake-active discharge profiles were mainly located lateral or dorsolateral to the SCN. This study shows heterogeneity of mouse SCN and surrounding anterior hypothalamic neurons and suggests differences in their topographic organization and roles in mammalian circadian rhythms and the regulation of sleep and wakefulness.

Cognition, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Sciences medicales, Medical sciences, Neurologie, Neurology, Maladies dégénératives et hérédodégénératives du système nerveux. Leucodystrophies. Maladies à prions, Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases, Acyltransferases, Encéphale, Encephalon, Encéfalo, Enzyme, Enzima, Maladie dégénérative, Degenerative disease, Enfermedad degenerativa, Maladie héréditaire, Genetic disease, Enfermedad hereditaria, Mammalia, Pathologie du système nerveux central, Central nervous system disease, Sistema nervosio central patología, Pathologie du système nerveux, Nervous system diseases, Sistema nervioso patología, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Transferases, Transmission synaptique, Synaptic transmission, Transmisión sináptica, Vertebrata, Acétylation, Acetylation, Acetilación, Animal transgénique, Transgenic animal, Animal transgénico, Ataxie spinocérébelleuse, Spinocerebellar ataxia, Ataxia spinocerebelosa, Cervelet, Cerebellum, Cerebelo, Dépression synaptique, Synaptic depression, Depresión sináptica, Histone acetyltransferase, Neurone Purkinje, Purkinje neuron, Neurona Purkinje, Plasticité synaptique, Synaptic plasticity, Plasticidad sináptica, Souris, Mouse, Ratón, Polyglutamine, Cerebellar long-term depression, Histone acetylation, Polyglutamine-expanded ataxin-3, and Spinocerebellar ataxia type 3

Our previous study using a transgenic mouse model of spinocerebellar ataxia type 3 (SCA3) reported that disease-causing ataxin-3-Q79 caused cerebellar malfunction by inducing transcriptional downregulation. Long-term depression (LTD) of parallel fiber-Purkinje neuron glutamatergic transmission is believed to be a cellular mechanism for motor learning and motor coordination in the cerebellum. Downregulated mRNA expression of calcineurin B, IP3-R1, myosin Va and PLC β4, which are required for the induction of cerebellar LTD, led to an impairment of LTD induction in Purkinje neurons of SCA3 transgenic mouse. Our study suggested that ataxin-3-Q79 caused hypoacetylation of cerebellar histone H3 or H4 by inhibiting the activity of histone acetyltransferase (HAT) without affecting the activity of histone deacetylase (HDAC). Consistent with the hypothesis that hypoacetylated H3 or H4 histone associated with promoter regions of downregulated genes is the molecular mechanism underlying ataxin-3-Q79-induced transcriptional repression, chromatin immunoprecipitation-quantitative real-time PCR analysis showed hypoacetylation of H3 or H4 histone associated with the proximal promoter of downregulated calcineurin B, IP3-R1, myosin Va or PLC β4 gene in the cerebellum of SCA3 mouse. HDAC inhibitor sodium butyrate reversed ataxin-3-Q79-induced hypoacetylation of histone H3 or H4 associated with the proximal promoter of calcineurin B, IP3-R1, myosin Va or PLC β4 gene. Sodium butyrate also prevented ataxin-3-Q79-induced impairment of LTD induction in Purkinje neurons of SCA3 mice. Our results suggest that polyglutamine-expanded ataxin-3-Q79 impairs HAT activity, leading to histone hypoacetylation, downregulated expression of cerebellar genes required for LTD induction and impaired induction of cerebellar LTD in the SCA3 transgenic mouse.

Cognition, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Encéphale, Encephalon, Encéfalo, Mammalia, Névroglie, Neuroglia, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, ATP, Adénosine, Adenosine, Adenosina, Animal, Astrocyte, Astrocito, Hippocampe, Hippocampus, Hipocampo, Induction, Inducción, Mutation, Mutación, Neurone, Neuron, Neurona, Protéine gliofibrillaire, Glial fibrillary acidic protein, Proteína gliofibrilar, Souris, Mouse, Ratón, Depotentiation, and LTP

Astrocytes regulate the activity of neighboring neurons by releasing chemical transmitters, including ATP. Adenosine levels in the cerebrospinal fluid of mice that express a mutant human glial fibrillary acidic protein in astrocytes are slightly elevated compared to those in wild type mice and this might result from the observed increased release by mutant astrocytes of ATP, which can be used to produce adenosine. Using hippocampal slices from these mutant mice, we examined whether the increased endogenous adenosine levels in the hippocampus modulate the reversal of long-term potentiation (LTP), i.e. depotentiation (DP), in CA1 neurons. In hippocampal slices from wild type mice, a stable LTP was induced by tetanic stimulation consisting of 100 pulses at 100 Hz, and this was reversed by a train of low frequency stimulation (LFS) of 500 pulses at 1 Hz applied 30 min later. This induction of DP was inhibited by application of either 100 nM adenosine or 0.5 nM N6-cyclopentyladenosine, an adenosine A1 receptor agonist, during LFS, indicating that the increase in extracellular adenosine levels attenuated DP induction by acting on adenosine A1 receptors. In contrast, although a stable LTP was also induced in hippocampal slices from mutant mice, induction of DP was inhibited, but DP could be induced by application, during LFS, of 50 nM 8-cyclopentyltheophylline, an adenosine A1 receptor antagonist. These results suggest that a small increase in extracellular adenosine levels resulting from increased ATP release by astrocytes results in attenuation of DP in hippocampal CA1 neurons in the mutant mice.

Neurology, Neurologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Développement. Sénescence. Régénération. Transplantation, Development. Senescence. Regeneration. Transplantation, Sciences medicales, Medical sciences, Neurologie, Neurology, Mammalia, Neuropeptide, Neuropéptido, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Animal, Cellule progéniteur, Progenitor cell, Célula progenitor, Cytodifférenciation, Cell differentiation, Diferenciación celular, Encéphale, Encephalon, Encéfalo, Galanine, Galanin, Galanina, Neurone, Neuron, Neurona, Olfaction, Olfación, Pathologie du système nerveux, Nervous system diseases, Sistema nervioso patología, Souris, Mouse, Ratón, Gal-KO, Neural progenitor cells, Neuronal differentiation, and SVZ-neurogenesis

Galanin is a pleiotropic neuropeptide widely expressed in the nervous system. It plays a role in many diverse physiological functions - including nociception, cognition and metabolism regulation - and acts as neurotrophic/ neuroprotective factor for several neuronal populations. In this article we sought to determine the role of galanin on neural stem cell function and its contribution to the plasticity of the nervous system. Here we show that galanin and its receptors are expressed in neural progenitor cells (NPCs) isolated from the developing striatum. Stimulation with galanin results in upregulation of Bcl-Xl, Bcl-2, Mash-1 and Olig-2 that are part of well known pro-survival/ pro-neuronal signalling pathways. Accordingly, treatment with galanin increases the number of neurons upon differentiation from these progenitors. We then show that these effects are recapitulated in NPCs isolated from the adult subventricular zone (SVZ), where galanin increases the total number of neurons and the number of newly-generated neurons upon differentiation in vitro. The significance of these findings is highlighted in the adult brain where loss of galanin leads to a marked decrease in the rate of adult SVZ neurogenesis and a reduction in the number of newly generated cells in the olfactory bulb. Interestingly, Gal-KO mice display normal performances in simple tasks of olfactory detection and discrimination, which points to the existence of a certain degree of redundancy in SVZ neurogenesis. Our findings establish the role of galanin as a modulator of neural stem cell function and support the importance of galanin for brain plasticity and repair.

Cognition, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Encéphale, Encephalon, Encéfalo, Mammalia, Mort cellulaire, Cell death, Muerte celular, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Animal, Apoptose, Apoptosis, Basse fréquence, Low frequency, Baja frecuencia, Champ électromagnétique, Electromagnetic field, Campo electromagnético, Hippocampe, Hippocampus, Hipocampo, Mémoire spatiale, Spatial memory, Memoria espacial, Neurogenèse, Neurogenesis, Neurogénesis, Neurone, Neuron, Neurona, Protéine amyloïde β, β Amyloid protein, Proteína amiloide β, Souris, Mouse, Ratón, Gène bax, Gène bcl2, Bax/Bcl-2 ratio, amyloid-β protein, apoptosis, neurogenesis, and spatial memory

In recent years, much effort has been devoted to identifying stimuli capable of enhancing adult neurogenesis, a process that generates new neurons throughout life, and that appears to be dysfunctional in the senescent brain and in several neuropsychiatric and neurodegenerative diseases. We previously reported that in vivo exposure to extremely low-frequency electromagnetic fields (ELFEFs) promotes the proliferation and neuronal differentiation of hippocampal neural stem cells (NSCs) that functionally integrate in the dentate gyrus. Here, we extended our studies to specifically assess the influence of ELFEFs on hippocampal newborn cell survival, which is a very critical issue in adult neurogenesis regulation. Mice were injected with 5-bromo-2'-deoxyuridine (BrdU) to label newborn cells, and were exposed to ELFEFs 9 days later, when the most dramatic decrease in the number of newly generated neurons occurs. The results showed that ELFEF exposure (3.5 h/day for 6 days) enhanced newborn neuron survival as documented by double staining for BrdU and doublecortin, to identify immature neurons, or NeuN labeling of mature neurons. The effects of ELFEFs were associated with enhanced spatial learning and memory. In an in vitro model of hippocampal NSCs, ELFEFs exerted their pro-survival action by rescuing differentiating neurons from apoptotic cell death. Western immunoblot assay revealed reduced expression of the pro-apoptotic protein Bax, and increased levels of the anti-apoptotic protein Bcl-2, in the hippocampi of ELFEF-exposed mice as well as in ELFEF-exposed NSC cultures, as compared with their sham-exposed counterparts. Our results may have clinical implications for the treatment of impaired neurogenesis associated with brain aging and neurodegenerative diseases.

Cognition, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Encéphale, Encephalon, Encéfalo, Enzyme, Enzima, Esterases, Hydrolases, Mammalia, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Triphosphoric monoester hydrolases, Vertebrata, ADP ribosylation, ADP ribosilación, Animal, Dendrite, Dendrita, Hippocampe, Hippocampus, Hipocampo, Localisation, Localization, Localización, Neurone, Neuron, Neurona, Souris, Mouse, Ratón, dGTPase, ADP-ribosylation factor, Endosome, Membrane traffic, Rab, and Small GTPase

Endosomal trafficking mediated by Rab11 and Arf6 small GTPases is essential for various neuronal functions. Family of Rab11-interacting protein 3 (FIP3)/Arfophilin-1, also termed Eferin, is a dual effector for Rab11 and Arf6 and implicated in endosomal trafficking during cytokinesis. To understand the neuronal functions of FIP3, we first showed the widespread neuronal expression of FIP3 mRNA in adult mouse brain by in situ hybridization. Immunohistochemical analysis showed the association of FIP3 with a subpopulation of endosomes labeled with EEA1 and syntaxin 12 in hippocampal neurons. Immunoblot analysis showed the progressive increase of FIP3 with a peak around postnatal day 15 during hippocampal development. Furthermore, knockdown of endogenous FIP3 decreased the total dendritic length of cultured hippocampal neurons with a concomitant increase in the number of short (<40 μm) primary dendrites. Together, FIP3 is suggested to regulate dendritic formation possibly through Rab11- and Arf6-mediated endosomal trafficking.

Cognition, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Catécholamine, Catecholamine, Catecolamina, Encéphale, Encephalon, Encéfalo, Mammalia, Neurotransmetteur, Neurotransmitter, Neurotransmisor, Noyau gris central, Basal ganglion, Núcleo basal, Rodentia, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Animal, Canal ionique, Ionic channel, Canal iónico, Dopamine, Dopamina, Inhibition, Inhibición, Neurone, Neuron, Neurona, Noyau accumbens, Nucleus accumbens, Núcleo acumbens, Potassium, Potasio, Souris, Mouse, Ratón, BK channels, Mice, and Potassium channels

Dopamine, a key neurotransmitter mediating the rewarding properties of drugs of abuse, is widely believed to exert some of its effects by modulating neuronal activity of nucleus accumbens (NAcc) medium spiny neurons (MSNs). Although its effects on synaptic transmission have been well documented, its regulation of intrinsic neuronal excitability is less understood. In this study, we examined the cellular mechanisms of acute dopamine effects on core accumbens MSNs evoked firing. We found that 0.5 μM A-77636 and 10 μM quinpirole, dopamine D1 (ORIs) and D2 receptor (D2Rs) agonists, respectively, markedly inhibited MSN evoked action potentials. This effect, observed only in about 25% of all neurons, was associated with spike-timing-dependent (STDP) long-term potentiation (tLTP), but not long-term depression (tLTD). Dopamine inhibits evoked firing by compromising subthreshold depolarization, not by altering action potentials themselves. Recordings in voltage-clamp mode revealed that all MSNs expressed fast (IA), slowly inactivating delayed rectifier (Idr), and large conductance voltage- and calcium-activated potassium (BKs) channels. Although A-77636 and quinpirole enhanced IA, its selective blockade by 0.5 μM phrixotoxin-1 had no effect on evoked firing. In contrast, exposing tissue to low TEA concentrations and to 10 μM paxilline, a selective BK channel blocker, prevented DIR agonist from inhibiting MSN firing. This result indicates that dopamine inhibits MSN firing through BK channels in a subpopulation of core accumbens MSNs exclusively associated with spike-timing-dependent long-term potentiation.

Cognition, Neurology, Neurologie, Physiology, morphology, Physiologie, morphologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Vertebres: systeme nerveux et organes des sens, Vertebrates: nervous system and sense organs, Système nerveux périphérique. Système nerveux autonome. Transmission neuromusculaire. Transmission ganglionnaire. Organe électrique, Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ, Aminoacide excitateur, Excitatory aminoacid, Aminoácido excitador, Encéphale, Encephalon, Encéfalo, Mammalia, Neurotransmetteur, Neurotransmitter, Neurotransmisor, Rodentia, Système nerveux autonome, Autonomic nervous system, Sistema nervioso autónomo, Système nerveux central, Central nervous system, Sistema nervioso central, Vertebrata, Animal, Bulbe rachidien, Medulla oblongata, Bulbo raquídeo, Glutamate, Glutamato, Mutation, Mutación, Neurone catécholaminergique, Catecholaminergic neuron, Neurona catecolaminérgica, Rhodopsine, Rhodopsin, Rodopsina, Souris, Mouse, Ratón, Stimulation, Estimulación, Système nerveux parasympathique, Parasympathetic nervous system, Sistema nervioso parasimpático, Optogénétique, Optogenetics, Transporteur glutamate VGLUT2, VGLUT2 glutamate transporter, C1 neuron, channel rhodopsin 2, conditional knockout, gene disruption in mice, and glutamate

Catecholaminergic neurons of the rostral ventrolateral medulla (RVLM-CA neurons; C1 neurons) contribute to the sympathetic, parasympathetic and neuroendocrine responses elicited by physical stressors such as hypotension, hypoxia, hypoglycemia, and infection. Most RVLM-CA neurons express vesicular glutamate transporter (VGLUT)2, and may use glutamate as a ionotropic transmitter, but the importance of this mode of transmission in vivo is uncertain. To address this question, we genetically deleted VGLUT2 from dopamine-β-hydroxylase-expressing neurons in mice [DβHCre/0;VGLUT2flox/flox mice (cKO mice)]. We compared the in vivo effects of selectively stimulating RVLM-CA neurons in cKO vs. control mice (DβHCre/0), using channelrhodopsin-2 (ChR2-mCherry) optogenetics. ChR2-mCherry was expressed by similar numbers of rostral ventrolateral medulla (RVLM) neurons in each strain (-400 neurons), with identical selectivity for catecholaminergic neurons (90-99% colocalisation with tyrosine hydroxylase). RVLM-CA neurons had similar morphology and axonal projections in DβHCre/0 and cKO mice. Under urethane anesthesia, photostimulation produced a similar pattern of activation of presumptive ChR2-positive RVLM-CA neurons in DpHCre/0 and cKO mice. Photostimulation in conscious mice produced frequency-dependent respiratory activation in DβHCre/0 mice but no effect in cKO mice. Similarly, photostimulation under urethane anesthesia strongly activated efferent vagal nerve activity in DβHCre/0 mice only. Vagal responses were unaffected by α1-adrenoreceptor blockade. In conclusion, two responses evoked by RVLM-CA neuron stimulation in vivo require the expression of VGLUT2 by these neurons, suggesting that the acute autonomic responses driven by RVLM-CA neurons are mediated by glutamate.