The Journal of neuroscience : the official journal of the Society for Neuroscience
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Using a spinal cord slice preparation and patch-clamp recordings from spinal cord dorsal horn neurons, we examined excitatory and inhibitory circuits connecting to lamina V neurons after the activation of afferent central terminal vanilloid receptor-1 (VR1) receptors and P2X receptors. We found that single neurons in lamina V often received excitatory inputs from two chemically defined afferent pathways. One of these pathways was polysynaptic from capsaicin-sensitive afferent terminals. ⋯ Both capsaicin-sensitive and alpha(beta)m-ATP-sensitive/capsaicin-insensitive pathways also recruited polysynaptic inhibitory inputs to lamina V neurons. Furthermore, we demonstrated that simultaneous activation of both capsaicin-sensitive afferent pathways and alpha(beta)m-ATP-sensitive/capsaicin-insensitive pathways could generate a temporal summation of excitatory inputs onto single lamina V neurons. These convergent pathways may provide a mechanism of sensory integration for two chemically defined sensory inputs and may have implications in different sensory states.
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Neuropathic pain (characterized by hyperalgesia and allodynia to mechanical and thermal stimuli) causes cellular changes in spinal dorsal horn neurons, some of which parallel those in synaptic plasticity associated with learning. Ubiquitin C-terminal hydrolase (UCH) appears to play a key role in long-term facilitation in Aplysia. The cooperation of UCH with the proteolytic enzyme complex known as the proteasome is required for the degradation of a number of signaling molecules within the cell that may remove normal restraints on synaptic plasticity. ⋯ Intrathecal administration of proteasome inhibitors attenuated hyperalgesia and allodynia in neuropathic rats. Expression of UCH-L1 (a rat homolog of Aplysia neuronal UCH and of the human UCH-L1, also known as PGP 9.5) and its mRNA were selectively increased within the ipsilateral dorsal horn of neuropathic rats, supporting the idea of a role for the ubiquitin-proteasome system in nociceptive processing. Proteasome inhibitors selectively attenuate allodynic and hyperalgesic responses in neuropathic pain, with some reduction in normal nociceptive, but not non-nociceptive responses, and potentially represent a novel therapeutic strategy for neuropathic pain.
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It is now well established that sensory neurons and receptors display characteristic morphological and electrophysiological properties tailored to their functions. This is especially evident in the auditory system, where cells are arranged tonotopically and are highly specialized for precise coding of frequency- and timing-dependent auditory information. Less well understood, however, are the mechanisms that give rise to these biophysical properties. ⋯ Exposure of neurons to BDNF caused all neurons, regardless of their original cochlear position, to display characteristics of the basal neurons. Conversely, NT-3 caused cells to show the properties of apical neurons. These results are consistent with oppositely oriented gradients of these two neurotrophins and/or their high-affinity receptors along the tonotopic map, and they suggest that a combination of neurotrophins are necessary to establish the characteristic firing features of postnatal spiral ganglion neurons.
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Dopaminergic neurotransmission in the nucleus accumbens (NAc) and neural processes in the basolateral (BLA) and central (CeN) amygdala nuclei are implicated in associative reward learning. Given their direct and indirect connections with the NAc and ventral tegmental area (VTA), both the BLA and CeN may regulate the mesoaccumbens dopamine (DA) system in rewarding situations. Electrical stimulation of the BLA (20 Hz, 10 sec, 300 microA) induced a long-lasting 25 +/- 4% increase in DA efflux in the NAc, measured by microdialysis in freely moving rats, whereas comparable stimulation of the CeN had no effect. ⋯ Additionally, infusions of lido (4%) into the medial prefrontal cortex failed to block the stimulation-evoked increase in NAc DA efflux. These data support the hypothesis that the BLA can directly modulate DA efflux through local mechanisms in the NAc, independent of an action on DA cell bodies in the VTA. The finding that brief activation of the CeN had no long-lasting effects on DA efflux in the NAc suggests an important degree of functional independence between the CeN and BLA.
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Traumatic axonal injury (TAI), a consequence of traumatic brain injury (TBI), results from progressive pathologic processes initiated at the time of injury. Studies attempting to characterize the pathology associated with TAI have not succeeded in following damaged and/or disconnected axonal segments back to their individual neuronal somata to determine their fate. To address this issue, 71 adult male Sprague Dawley rats were subjected to moderate central fluid percussion injury and killed between 30 min and 7 d after injury. ⋯ When followed 7 d after injury, these abnormalities did not reveal dramatic progression. Rather, some somata showed evidence of potential reorganization and repair. This study demonstrates a novel somatic response to TAI in the perisomatic domain and also provides insight into the multifaceted pathology associated with TBI.