Journal of neurophysiology
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The effect of early postnatal blockade of neuromuscular transmission using botulinum neurotoxin (BoNT) type A on motoneuron gap junctional coupling was studied by means of intracellular recordings and biocytin labeling using the in vitro hemisected spinal cord preparation of neonatal rats. The somata of tibialis anterior (TA) motoneurons were retrogradely labeled at birth (P0) by intramuscular injection of fluorescent tracers. Two days later, BoNT was injected unilaterally into the TA muscle. ⋯ The dye-coupled neurons clustered around the injected cell with close somato-somatic, dendro-somatic and -dendritic appositions that might represent the sites of electrotonic coupling. The size of the motoneuron cluster was, on average, 2.2 times larger after BoNT treatment. Our findings demonstrate that a short-lasting functional disconnection of motoneurons from their target muscle delays motoneuron maturation by halting the elimination of gap junctional coupling that normally occurs during early postnatal development.
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Although the entire output of the cerebellar cortex is conveyed to the deep cerebellar nuclei neurons (DCNs) via the GABAergic synapses established by Purkinje cells (PCs), very little is known about the strength and dynamic properties of PC-DCN connections. Here we show that activation of PC-DCN unitary connections induced large conductance changes (11.7 nS) in DCNs recorded in whole cell patch configuration in acute slices, suggesting that activity of single PCs might significantly affect the output of its target neurons. Based on the large unitary quantal content (18) inferred from calculations of PC-DCN quantal size (0.65 nS) and the near absence of failures in synaptic transmission during control conditions, we conclude that PC-DCN connections are highly multi-sited. ⋯ In addition, multiple pulse stimulation revealed that PC-DCN synapses exhibited larger sensitivity to dynamic than to steady signals. We postulate that the, otherwise paradoxical, combination of marked short-term depression with strong multi-sited connections is optimal to transfer dynamic information at unitary level by performing spatial average of release probability across the numerous release sites. This feature could enable these synapses to encode presynaptic time-varying signals of single PCs as moment-to-moment changes in synaptic strength, a capacity well suited to the postulated role of cerebellum in control of temporal aspects of motor or cognitive behaviors.
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Substance P (SP) is an undecapeptide that is co-localized with conventional transmitters in the nucleus accumbens (NAc). Its neurochemical and behavioral effects resemble those of cocaine and amphetamine. How SP accomplishes these effects is not known, partly because its cellular and synaptic effects are not well characterized. ⋯ In addition, the SP-induced synaptic depression was blocked by an adenosine A1 receptor blocker 8-cyclopentyltheophylline (8-CPT) but not the N-methyl-D-aspartate (NMDA) receptor antagonist D-APV. These data show that SP, by activating presynaptic NK1 receptors, depresses excitatory synaptic transmission indirectly by enhancing extracellular dopamine and adenosine levels. Since the cellular and synaptic effects of SP resemble those of cocaine and amphetamine, it may serve as an endogenous psychogenic peptide.
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A total of 20 right-handed subjects were asked to perform a grasp-lift-and-hold task using a precision grip. The grasped object was a one-degree-of-freedom manipuladum consisting of a vertically mounted linear motor capable of generating resistive forces to simulate a range of object weights. In the initial study, seven subjects (6 women, 1 man; ages 24-56 yr) were first asked to lift and hold the object stationary for 4 s. ⋯ Vision of the grasping hand did not significantly correct the finger misalignment after digital anesthesia. Taken together, these results suggest that mechanoreceptors in the fingertips signal the source and direction of pressure applied to the skin. The nervous system uses this information to adjust the fingers and direct the pinch forces optimally for grasping and object manipulation.
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Recently we have shown that acute ethanol (EtOH) exposure suppresses dorsal root-evoked synaptic potentials in spinal motoneurons. To examine the synaptic mechanisms underlying the reduced excitatory activity, EtOH actions on properties of action potential-independent miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) were studied in spinal motoneurons of newborn rats. Properties of mEPSCs generated by activation of N-methyl-D-aspartate receptors (NMDARs) and non-NMDA receptors and of mIPSCs mediated by glycine and gamma-aminobutyric acid-A receptors (GlyR and GABA(A)R) were examined during acute exposure to 70 and 200 mM EtOH. ⋯ Exposure to the higher EtOH concentration had opposite actions on mEPSC and mIPSC amplitudes: it attenuated the amplitude of NMDAR- and non-NMDAR-mediated mEPSCs to ~80% of control and increased GlyR- and GABA(A)R-mediated mIPSC amplitude by ~20%. EtOH-induced changes in the amplitude of postsynaptic currents were not associated with changes in their basic kinetic properties. Our data suggested that in spinal networks of newborn rats, EtOH was more effective in modulating the release of excitatory and inhibitory neurotransmitters than changing the properties of their receptors/channels.