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Glutamatergic synaptic transmission is a dynamic process determined by the amount of glutamate released by presynaptic sites, the clearance of glutamate in the synaptic cleft, and the properties of postsynaptic glutamate receptors. Clearance of glutamate in the synaptic cleft depends on passive diffusion and active uptake by glutamate transporters. In this study, we examined the role of glial glutamate transporter 1 (GLT-1) in spinal sensory processing. Excitatory postsynaptic currents (EPSCs) of substantia gelatinosa neurons recorded from spinal slices of young adult rats were analyzed before and after GLT-1 was pharmacologically blocked by dihydrokainic acid. Inhibition of GLT-1 prolonged the EPSC duration and the EPSC decay phase. The EPSC amplitudes were increased in neurons with weak synaptic input but decreased in neurons with strong synaptic input upon inhibition of GLT-1. We suggest that presynaptic inhibition, desensitization of postsynaptic AMPA receptors, and glutamate "spillover" contributed to the kinetic change of EPSCs induced by the blockade of GLT-1. Thus, GLT-1 is a key component in maintaining the spatial and temporal coding in signal transmission at the glutamatergic synapse in substantia gelatinosa neurons.

Changes in the signaling of wide dynamic range neurons and the expression of glutamate transporters in the lumbar spinal dorsal horn of rats with Taxol-induced hyperalgesia are detailed in this report. Deep spinal lamina neurons have significantly increased spontaneous activity and after-discharges to noxious mechanical stimuli, increased responses to both skin heating and cooling, and increased after-discharges and abnormal windup to transcutaneous electrical stimuli. The expression of glutamate transporter proteins in the dorsal horn is decreased at the time point corresponding to the physiological changes. These results suggest a state of increased excitability develops in spinal pain-signaling neurons as a consequence of decreased glutamate clearance. These changes in dorsal horn neurobiology likely in turn contribute to the hyper-responsiveness to sensory stimuli seen in animals treated with Taxol and may play a role in the pain seen in cancer patients receiving Taxol.

The importance of spike bursts in thalamo-cortical processing of sensory information has received an increasing amount of interest over the past several years. Previously it has been reported that short high-frequency spike trains (3-8 action potentials occurring at 67-167 Hz), or spike bursts, are increased in both human and non-human primate thalamus following deafferentation. Here we examine the effects of lesion of the ventral spinal quadrant alone versus combined lesion of the ventral and dorsal spinal quadrants on the evoked and spontaneous spike trains in thalamic neurons. A total of 1175 neurons were sampled from 13 animals, three intact, six with ventral quadrant lesions (three with prolonged survival and three with short-term survival after spinal lesion) and four with combined ventral and dorsal quadrant lesions. Detailed analysis was conducted on 256 of these neurons, which revealed that thalamic neurons of animals with ventral quadrant lesions had elevated burst and non-burst spike rates while neurons from animals with combined ventral-dorsal lesions showed two types of change. Neurons in the forelimb areas showed increased bursts without a change in non-burst activity, while neurons in lateral VPL without receptive fields showed very low non-burst activity, but high burst spike rates. The magnitude of the effects produced by ventral-lateral spinal lesions was more pronounced in the short-term survival animals than in the long-term survival animals. These results show that the effects of deafferentation on the physiological properties of thalamic neurons are dependent on the afferent tract or tracts that are lesioned and the time after lesion.

The long-term consequences of thoracic spinothalamic tract lesion on the physiological properties of neurons in the ventral posterior lateral nucleus of the thalamus in monkeys were assessed. Neurons responding to both compressive and phasic brush stimuli (multireceptive neurons), but not brush-specific (low-threshold) neurons, in the partially deafferented thalamus showed increased spontaneous activity, increased responses evoked by cutaneous stimuli and larger mean receptive field size than the same types of cells in the thalamus with intact innervation. The spike train properties of both the spontaneous and evoked discharges of cells were also altered so that there was an increased incidence of spike-bursts in cells of deafferented thalamus. These changes were widespread in the thalamus, and included cells in both the fully innervated forelimb representation and the partially denervated hindlimb representation ipsilateral to the lesion. The spontaneous and evoked spike trains in the ipsilateral thalamus also show increased frequency of both spike-burst and non-burst events compared to the intact thalamus. These results indicate that chronic spinothalamic tract lesion produces widespread changes in the physiological properties of a discrete cell population of the thalamus.The findings in this study indicate that the thalamic processing of somatosensory information conveyed by the lemniscal system is altered by transection of the spinothalamic tract. This change in sensory processing in the thalamus would result in altered cortical processing of innocuous somatosensory inputs following deafferentation and so possibly contribute to the generation of the central pain syndrome.

The withdrawal reflex pathways to hindlimb muscles have an elaborate spatial organization in the rat. In short, the distribution of sensitivity within the cutaneous receptive field of a single muscle has a spatial pattern that is a mirror image of the spatial pattern of the withdrawal of the skin surface ensuing on contraction in the respective muscle. In the present study, a search for neurones encoding the specific spatial input-output relationship of withdrawal reflexes to single muscles was made in the lumbosacral spinal cord in halothane/nitrous oxide-anaesthetized rats. The cutaneous receptive fields of 147 dorsal horn neurones in the L4-5 segments receiving a nociceptive input and a convergent input from A and C fibres from the hindpaw were studied. The spatial pattern of the response amplitude within the receptive fields of 118 neurones was quantitatively compared with those of withdrawal reflexes to single muscles. Response patterns exhibiting a high similarity to those of withdrawal reflexes to single muscles were found in 27 neurones located in the deep dorsal horn. Twenty-six of these belonged to class 2 (responding to tactile and nociceptive input) and one belonged to class 3 (responding only to nociceptive input). None of the neurones tested (n = 20) with reflex-like response patterns could be antidromically driven from the upper cervical cord, suggesting that they were spinal interneurones. With some overlap, putative interneurones of the withdrawal reflexes to the plantar flexors of the digits, the plantar flexors of the ankle, the pronators, the dorsiflexors of the ankle, and a flexor of the knee, were found in succession in a mediolateral direction.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional plasticity in receptive field properties underlies the mechanism whereby spinal dorsal horn neurons encode changes in pain sensitivity following peripheral injury. Activation of “silent” or subliminal excitatory synapses was hypothesized to account for this injury-induced neural plasticity. To better characterize the mechanisms governing subliminal inputs, we adapted whole-cell patch clamp to the study of dorsal horn neurons in intact, anesthetized rats. In this report we show that the membrane properties of spinal cells correlate to functional class defined by action potential responses to cutaneous stimuli. In addition, we report the discovery of a novel “silent” population of neurons with solely subliminal excitatory inputs at rest that can be activated by membrane depolarization. Finally, an induced change in baseline membrane potential to a level nearer that of a different functional class results in a corresponding change in the responses to cutaneous stimuli of a given cell to that of the new functional class. In summary our findings suggest that biophysical membrane properties are key factors determining the functional profile of spinal neurons. The rapid change of such properties may regulate the function of silent synapses in spinal neurons and underlie rapid development of neural plasticity. [Copyright &y& Elsevier]