Neuroscience
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N-methyl-D-aspartate receptors (NMDARs) are glutamatergic by virtue of glutamate-binding GluN2 subunits and glycinergic by virtue of glycine-binding GluN1 and GluN3 subunits. The existence, location, and functional-significance of NMDARs containing both GluN2 and GluN3 subunits have as yet remained unelucidated. ⋯ Pharmacology revealed a triheteromeric-receptor with features common to glutamate-activated GluN1/GluN2-containing and glycine-activated GluN1/GluN3-containing diheteromeric NMDARs. However, unlike GluN1/GluN3 receptors, NMDARs at L1 inputs were activated by glutamate and blocked by d-AP5, Ca(2+)-permeable, and more efficient at integrating and potentiating EPSPs selectively over Str inputs during high-frequency stimulation while obviating the need for AMPAR-mediated depolarization.
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The distribution of low-threshold tetrodotoxin-resistant (TTX-r) Na(+) current and its co-expression with high-threshold TTX-r Na(+) current were studied in randomly selected acutely dissociated rat trigeminal ganglion (non-identified TG cells) and TG cells serving the temporomandibular joint (TMJ-TG cells). Conditions previously shown to enhance Na(V)1.9 channel-mediated currents (holding potential (HP) -80 mV, 130-mM fluoride internally) were employed to amplify the low-threshold Na(+) current. Under these conditions, detectable low-threshold Na(+) current was exhibited by 16 out of 21 non-identified TG cells (average, 1810 ± 358 pA), and by nine of 14 TMJ-TG cells (average, 959 ± 525 pA). ⋯ In TG cells expressing prominent low-threshold Na(+) currents, changing the external solution to one containing 0 mM Na(+) reduced the amount of current required to hold the cells at -80 mV through -50 mV, the peak effect being observed at HP -60 mV. TG cells recorded from with a more physiological pipette solution containing chloride instead of fluoride exhibited small low-threshold Na(+) currents, which were greatly increased upon superfusion of the TG cells with the adenylyl cyclase (AC) activator forskolin. These data suggest two hypotheses: (1) low- and high-threshold Na(V)1.9 and Na(V)1.8 channels, respectively, are frequently co-expressed in TG neurons serving the TMJ and other structures, and (2), Na(V)1.9 channel-mediated currents are small under physiological conditions, but may be enhanced by inflammatory mediators that increase AC activity, and may mediate an inward leak that depolarizes TG neurons, increasing their excitability.
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Arginine-vasopressin (AVP) and the vasopressin 1a receptor (V1aR) modulate social behavior and learning and memory in adult animals. Both functions depend upon the normal emergence of the balance of excitation and inhibition (E/I balance) in the neocortex. Here, we tested the hypothesis that V1aR signaling and E/I balance converge through the influence of the neuropeptide on interneuron number achieved in the neocortex. ⋯ Receptor binding levels in these cortical structures fell dramatically in the adult, maintaining high levels of expression subcortically. Surprisingly, we observed sex differences in the number of calbindin interneurons, and a contribution of V1aR to the number of parvalbumin-immunoreactive neurons in the adult mouse neocortex. These data suggest that individual differences in developmentally transient V1aR signaling and even sex may alter the development of E/I balance in the neocortex, with long-lasting influence on information processing.
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Excitotoxicity triggered by over-stimulation of glutamatergic receptors is considered to be a major component of damage following acute spinal cord injury (SCI). Using an in vitro model of neonatal rat SCI caused by transient application (1h) of the glutamate agonist kainate (0.05-0.1 mM) to produce limited excitotoxicity, the present study investigated whether riluzole, a drug inhibiting glutamate release and neuronal excitability, could prevent neuronal loss and protect locomotor patterns 24 h later. Immunohistochemical analysis of neuronal and motoneuronal populations was associated with recording of fictive locomotion induced by neurochemicals or dorsal root stimuli. ⋯ When this protocol was implemented after kainate, no efficient histological or functional recovery was observed. No additional benefit was detected even when riluzole was co-applied with kainate and continued for the following 3 h. These results show that modest neuronal losses evoked by excitotoxicity have a severe impact on locomotor network function, and that they cannot be satisfactorily blocked by strong neurodepression with riluzole, suggesting the need for more effective pharmacological approaches.
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The aim of this study was to explore, during adolescence, alterations in the use of a sensori-motor representation as unveiled by the measurement of anticipatory postural control in a bimanual load-lifting task. We hypothesised that adolescence constitutes a period of refinement of anticipatory postural control due to on-going updates of the body schema and sensori-motor representations. The anticipatory postural control was assessed using a bimanual load-lifting paradigm in which subjects stabilise their left postural forearm, which is supporting an object, while they use their right hand to lift up the object. ⋯ The decrease of activity over postural flexors, which ensure postural stabilisation, appeared later in adolescents with respect to adults. Delayed timing adjustments and increased variability could reflect intense developmental processes underlain by an intense period of CNS maturation during adolescence. We discuss the role of brain maturation in the refinement of sensori-motor representations and the update of body schema.