Journal of neurophysiology
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Randomized Controlled Trial
Modulation of soleus H reflex by spinal DC stimulation in humans.
Transcranial direct current stimulation (tDCS) of the human motor cortex induces changes in excitability within cortical and spinal circuits that occur during and after the stimulation. Recently, transcutaneous spinal direct current stimulation (tsDCS) has been shown to modulate spinal conduction properties, as assessed by somatosensory-evoked potentials, and transynaptic properties of the spinal neurons, as tested by postactivation depression of the H reflex or by the RIII nociceptive component of the flexion reflex in the lower limb. To further explore tsDCS-induced plastic changes in spinal excitability, we examined, in a double-blind crossover randomized study, the stimulus-response curves of the soleus H reflex before, during, at current offset and 15 min after anodal, cathodal, and sham tsDCS delivered at the Th11 level (2.5 mA, 15 min, 0.071 mA/cm(2), 0.064 C/cm(2)) in 17 healthy subjects. ⋯ In contrast, both cathodal and sham tsDCS had no significant effects. This exploratory study provides further evidence for the use of tsDCS as an expedient, noninvasive tool to induce long-lasting plastic changes in spinal circuitry. Increased spinal excitability after anodal tsDCS may have potential for spinal neuromodulation in patients with central nervous system lesions.
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Deep brain stimulation (DBS) in the globus pallidus internus (GPi) has been shown to improve dystonia, a movement disorder of repetitive twisting movements and postures. DBS at frequencies above 60 Hz improves dystonia, but the mechanisms underlying this frequency dependence are unclear. In patients undergoing dual-microelectrode mapping of the GPi, microstimulation has been shown to reduce neuronal firing, presumably due to synaptic GABA release. ⋯ Post-HFS, overall firing was reduced compared with pre-HFS, and the fEP amplitudes were enhanced at low frequencies, providing evidence of inhibitory synaptic plasticity in the GPi. In a patient with DBS electrodes already implanted in the GPi, recordings from four neurons in the subthalamic nucleus showed almost complete inhibition of firing with clinically effective but not clinically ineffective stimulation parameters. These data provide additional support for the hypothesis of stimulation-evoked GABA release from afferent synaptic terminals and reduction of neuronal firing during DBS and additionally, implicate excitation of GPi axon fibers and neurons and enhancement of inhibitory synaptic transmission by high-frequency GPi DBS as additional putative mechanisms underlying the clinical benefits of DBS in dystonia.
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Calcitonin gene-related peptide (CGRP) is regarded as a key mediator in the generation of primary headaches. CGRP receptor antagonists reduce migraine pain in clinical trials and spinal trigeminal activity in animal experiments. The site of CGRP receptor inhibition causing these effects is debated. ⋯ In conclusion, the activity of spinal trigeminal neurons with meningeal afferent input is normally not controlled by CGRP receptor activation or inhibition in the trigeminal ganglion. CGRP receptors in the trigeminal ganglion may influence neuronal activity evoked by mechanical stimulation of meningeal afferents only after pretreatment with GTN. Since it has previously been shown that olcegepant applied to the cranial dura mater is ineffective, trigeminal activity driven by meningeal afferent input is more likely to be controlled by CGRP receptors located centrally to the trigeminal ganglion.
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Comparative Study
A neuronal population in hypothalamus that dramatically resists acute ischemic injury compared to neocortex.
Pyramidal neurons (PyNs) of the cortex are highly susceptible to acute stroke damage, yet "lower" brain regions like hypothalamus and brain stem better survive global ischemia. Here we show for the first time that a "lower" neuron population intrinsically resists acute strokelike injury. In rat brain slices deprived of oxygen and glucose (OGD), we imaged anoxic depolarization (AD) as it propagated through neocortex or hypothalamus. ⋯ Moreover, elevated extracellular K(+) concentration ([K(+)](o)) evokes spreading depression (SD), a milder version of AD, in PyNs but not MNCs. Therefore overriding the pump by OGD, ouabain, or elevated [K(+)](o) evokes a propagating depolarization in higher gray matter but not in MNCs. We suggest that variation in Na(+)-K(+)-ATPase pump efficiency during ischemia injury determines whether a neuronal type succumbs to or resists stroke.
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Rapid temporal modulation of acoustic signals among several vertebrate lineages has recently been shown to depend on the actions of superfast muscles. We hypothesized that such fast events, known to require synchronous activation of muscle fibers, would rely on motoneuronal properties adapted to generating a highly synchronous output to sonic muscles. Using intracellular in vivo recordings, we identified a suite of premotor network inputs and intrinsic motoneuronal properties synchronizing the oscillatory-like, simultaneous activation of superfast muscles at high gamma frequencies in fish. ⋯ Differential motoneuron recruitment led, however, to amplitude modulation (AM) of vocal output and, hence, natural call AM. In summary, motoneuronal intrinsic properties, in particular low excitability, predisposed vocal motoneurons to the synchronizing influences of premotor inputs to translate a temporal input code into a coincident and extremely synchronous, but variable-amplitude, output code. We propose an analogous suite of neuronal properties as a key innovation underlying similarly rapid acoustic events observed among amphibians, reptiles, birds, and mammals.