Journal of neurophysiology
-
Phantom sensations and sensory hypersensitivity are disordered perceptions that characterize a variety of intractable conditions involving the somatosensory, visual, and auditory modalities. We report physiological correlates of two perceptual abnormalities in the auditory domain: tinnitus, the phantom perception of sound, and hyperacusis, a decreased tolerance of sound based on loudness. Here, subjects with and without tinnitus, all with clinically normal hearing thresholds, underwent 1) behavioral testing to assess sound-level tolerance and 2) functional MRI to measure sound-evoked activation of central auditory centers. ⋯ The results directly link hyperacusis and tinnitus to hyperactivity within the central auditory system. We hypothesize that the tinnitus-related elevations in cortical activation may reflect undue attention drawn to the auditory domain, an interpretation consistent with the lack of tinnitus-related effects subcortically where activation is less potently modulated by attentional state. The data strengthen, at a mechanistic level, analogies drawn previously between tinnitus/hyperacusis and other, nonauditory disordered perceptions thought to arise from neural hyperactivity such as chronic neuropathic pain and photophobia.
-
Following spinal cord injury (SCI) neurons caudal to the injury are capable of rhythmic locomotor-related activity that can form the basis for substantial functional recovery of stepping despite the loss of crucial brain stem-derived neuromodulators like serotonin (5-HT). Here we investigated the contribution of constitutive 5-HT(2) receptor activity (activity in the absence of 5-HT) to locomotion after SCI. We used a staggered hemisection injury model in rats to study this because these rats showed a robust recovery of locomotor function and yet a loss of most descending axons. ⋯ However, even in the most severely impaired animals, rhythmic sweeping movements of the hindlimb feet were still visible during forelimb locomotion, suggesting that SB206553 did not completely eliminate locomotor drive to the motoneurons or motoneuron excitability. The same application of SB206553 had no affect on stepping in normal rats. Thus while normal rats can compensate for loss of 5-HT(2) receptor activity, after severe spinal cord injury rats require constitutive activity in these 5-HT(2) receptors to produce locomotion.
-
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by pain and hypersensitivity in the relative absence of colon inflammation or structural changes. To assess the role of P2X receptors expressed in colorectal dorsal root ganglion (c-DRG) neurons and colon hypersensitivity, we studied excitability and purinergic signaling of retrogradely labeled mouse thoracolumbar (TL) and lumbosacral (LS) c-DRG neurons after intracolonic treatment with saline or zymosan (which reproduces 2 major features of IBS-persistent colorectal hypersensitivity without inflammation) using patch-clamp, immunohistochemical, and RT-PCR techniques. Although whole cell capacitances did not differ between LS and TL c-DRG neurons and were not changed after zymosan treatment, membrane excitability was increased in LS and TL c-DRG neurons from zymosan-treated mice. ⋯ The number of cells expressing P2X(3) protein and its mRNA and the kinetic properties of ATP- and α,β-meATP-evoked currents in c-DRG neurons were not changed by zymosan treatment. However, the EC(50) of α,β-meATP for the fast current decreased significantly in TL c-DRG neurons. These findings suggest that colorectal hypersensitivity produced by intracolonic zymosan increases excitability and enhances purinergic signaling in c-DRG neurons.
-
Bidirectional changes in synaptic transmission have the potential to optimize the control of movement. However, it can be difficult to establish a causal relationship between the bidirectionality of synaptic plasticity and bidirectional changes in the speed of actual movements. We asked whether metabotropic glutamate receptor 1 (mGluR1) receptors, which participate in cerebellar long-term depression (LTD), are necessary for bidirectional motor learning in the vestibulo-ocular reflex (VOR). ⋯ Gain-down learning was not significantly affected by either drug. These results supported the hypothesis that gain-up learning relies on cerebellar LTD, but gain-down learning relies on a different mechanism. In the absence of mGluR1 activity, cerebellar LTD may be replaced with LTP, permitting learning in only one direction.
-
Comparative Study
Behavior of the oculomotor vermis for five different types of saccade.
Single unit and lesion studies have implicated the oculomotor vermis of the cerebellum in the control of targeting saccades to jumping visual targets. However, saccades can be made in a variety of other target situations where they can occur with different reaction times (express or delayed saccades) in response to a remembered target location (memory-guided saccades) or between several targets that are always visible (scanning saccades). Here we ask whether the oculomotor vermis contributes to generating all these types of saccades by examining the simple spike discharge of its Purkinje cells. ⋯ Although a sensitive test of discharge patterns revealed significant differences for some pairs of saccade types in ∼29% of P-cells, there was no cell-to-cell consistency as to which pairs were associated with different patterns. Also, a less sensitive comparison identified substantially fewer cells (∼15%) with different patterns. Thus the lack of any consistent difference in firing for different saccade types leads us to conclude that the oculomotor vermis is not likely to contribute differently to targeting, express, scanning, delayed, or memory-guided saccades.