Journal of neurophysiology
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Central pain syndrome (CPS) is a debilitating condition that affects a large number of patients with a primary lesion or dysfunction in the CNS, most commonly due to spinal cord injury, stroke, and multiple sclerosis lesions. The pathophysiological processes underlying the development and maintenance of CPS are poorly understood. We have recently shown, in an animal model of CPS, that neurons in the posterior thalamic nucleus (PO) have increased spontaneous and evoked activity. ⋯ This increase was due to a selective increase in firing of tonic neurons that project to and inhibit ZI and an increase in bursts in fast bursting and slow rhythmic neurons. We also show that, in normal animals, suppressing APT results in increased PO spontaneous activity and evoked responses in a subpopulation of PO neurons. Taken together, these findings suggest that APT regulates ZI inputs to PO and that enhanced APT activity during CPS contributes to the abnormally high activity of PO neurons in CPS.
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The pedunculopontine nucleus (PPN) is part of the cholinergic arm of the reticular activating system, which is mostly active during waking and rapid-eye movement sleep. The PPN projects to the thalamus and receives cholinergic inputs from the laterodorsal tegmental nucleus and contralateral PPN. We employed retrograde labeling and whole cell recordings to determine the modulation of GABAergic, glycinergic, and glutamatergic transmission to PPN thalamic projecting neurons, and their postsynaptic responses to the nonspecific cholinergic agonist carbachol. ⋯ Decreases in the frequency of miniature EPSCs, and amplitude of electrical stimulation-evoked EPSCs, were blocked by a M2 antagonist, suggesting the presence of M2Rs at terminals of presynaptic glutamatergic neurons. Carbachol-induced multiple types of postsynaptic responses, enhancing both inhibitory and excitatory fast transmission to PPN thalamic projecting neurons through muscarinic receptors. These results provide possible implications for the generation of different frequency oscillations in PPN thalamic projecting neurons during distinct sleep-wake states.
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Glial cell dysfunction and excessive glutamate receptor activation in spinal dorsal horn neurons are hallmark mechanisms of pathological pain. The way in which glial cell dysfunction leads to excessive glutamate receptor activation in the spinal sensory synapses remains unknown. We and others recently reported the downregulation of glial glutamate transporter (GT) protein expression in the spinal dorsal horn of neuropathic rats. ⋯ Pharmacological blockade of glial GTs with dihydrokainic acid enhanced NMDA receptor activation elicited by synaptic input or puffed glutamate in normal control rats, but this effect was precluded in neuropathic rats. Thus extrasynaptic glutamate spillover and extrasynaptic NMDA receptor activation induced by deficient glial glutamate uptake in the synapses resulted in the excessive activation of NMDA receptors in neuropathic rats. It is suggested that extrasynaptic glutamate spillover may be a key synaptic mechanism related to phenotypic alterations induced by nerve injury in the spinal dorsal horn and that glial GTs are potential new targets in the development of analgesics.
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Cortical sound representations are adapted to the acoustic environment. Early exposure to exponential frequency-modulated (FM) sweeps results in more neurons selective to the experienced sounds. Here we examined the influence of pulsed noise experience on the development of sound representations in the primary auditory cortex (AI) of the rat. ⋯ In addition, AI tonotopicity, tuning bandwidth, intensity threshold, tone-responsiveness, and sweep response magnitude were differentially affected by the noise experience depending on the exposure time windows. These results are consistent with previous findings of feature-dependent multiple sensitive periods. The different effects induced here by pulsed noise and previously by FM sweeps further indicate that plasticity in cortical complex sound representations is specific to the sensory input.
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beta-Adrenoceptors play a crucial role in the regulation of taste aversion learning in the insular cortex (IC). However, beta-adrenergic effects on inhibitory synaptic transmission mediated by gamma-aminobutyric acid (GABA) remain unknown. To elucidate the mechanisms of beta-adrenergic modulation of inhibitory synaptic transmission, we performed paired whole cell patch-clamp recordings from layer V GABAergic interneurons and pyramidal cells of rat IC aged from postnatal day 17 (PD17) to PD46 and examined the effects of isoproterenol, a beta-adrenoceptor agonist, on unitary inhibitory postsynaptic currents (uIPSCs). ⋯ There was no significant correlation between age and changes of uIPSCs in LTS-/LS-pyramidal cell pairs. These results suggest the presence of differential mechanisms in presynaptic GABA release and/or postsynaptic GABA(A) receptor-related assemblies among interneuron subtypes. Age- and interneuron subtype-specific beta-adrenergic modulation of IPSCs may contribute to experience-dependent plasticity in the IC.