Neuroscience
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Our aim was to enhance the spontaneous slow-frequency EEG activity during the resting state using oscillating transcranial direct currents (tDCS) with a stimulation frequency that resembles the spontaneous oscillations of sleep onset. Accordingly, in this preliminary study, we assessed EEG after-effects of a frontal oscillatory tDCS with different frequency (0.8 vs. 5 Hz) and polarity (anodal, cathodal, and sham). Two single-blind experiments compared the after effects on the resting EEG of oscillatory tDCS [Exp. 1=0.8 Hz, 10 subjects (26.2 ± 2.5 years); Exp. 2=5 Hz, 10 subjects (27.4 ± 2.4 years)] by manipulating its polarity. ⋯ We have shown that a frontal oscillating anodal tDCS at 5 Hz results in an effective change of both subjective sleepiness and spontaneous slow-frequency EEG activity. These changes are critically associated to both stimulation polarity (anodal) and frequency (5 Hz). However, evidence of frequency-dependence seems more unequivocal than evidence of polarity-dependence.
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Intrinsic plasticity has emerged as an important mechanism regulating neuronal excitability and output under physiological and pathological conditions. Here, we report a novel form of intrinsic plasticity. Using perforated patch clamp recordings, we examined the modulatory effects of group II metabotropic glutamate receptors (mGluR II) on voltage-gated potassium (KV) currents and the firing properties of neurons in the chicken nucleus laminaris (NL), the first central auditory station where interaural time cues are analyzed for sound localization. ⋯ The intracellular mechanism involved the Gβγ signaling pathway associated with phospholipase C and protein kinase C. The modulation strengthened membrane outward rectification, sharpened action potentials, and improved the ability of NL neurons to follow high-frequency inputs. These data suggest that mGluR II provides a feedforward modulatory mechanism that may regulate temporal processing under the condition of heightened synaptic inputs.
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This study was designed to investigate brain connections among chemosensitive areas in newborn rats. Rhodamine beads were injected unilaterally into the locus coeruleus (LC) or into the caudal part of the nucleus tractus solitarius (cNTS) in Sprague-Dawley rat pups (P7-P10). Rhodamine-labeled neurons were patched in brainstem slices to study their electrophysiological responses to hypercapnia and to determine if chemosensitive neurons are communicating between LC and cNTS regions. ⋯ Extensive anatomical connections among chemosensitive brainstem regions in newborn rats were found and at least for the LC and cNTS, the connections involve some CO2-sensitive neurons. Such anatomical and functional coupling suggests a complex central respiratory control network, such as seen in adult rats, is already largely present in neonatal rats by at least day P7-P10. Since the NTS and the LC play a major role in memory consolidation, our results may also contribute to the understanding of the development of memory consolidation.
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Tic disorders, including Tourette syndrome (TS), are thought to involve pathology of cortico-basal ganglia loops, but their pathology is not well understood. Post-mortem studies have shown a reduced number of several populations of striatal interneurons, including the parvalbumin-expressing fast-spiking interneurons (FSIs), in individuals with severe, refractory TS. We tested the causal role of this interneuronal deficit by recapitulating it in an otherwise normal adult mouse using a combination transgenic-viral cell ablation approach. ⋯ FSI ablation also led to increased anxiety-like behavior in the elevated plus maze, but not to alterations in motor learning on the rotorod or to alterations in prepulse inhibition, a measure of sensorimotor gating. These findings indicate that a striatal FSI deficit can produce stress-triggered repetitive movements and anxiety. These repetitive movements may recapitulate aspects of the pathophysiology of tic disorders.
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Chronic treatment with the monoamine releaser d-amphetamine has been consistently shown to decrease cocaine self-administration in laboratory studies and clinical trials. However, the abuse potential of d-amphetamine is an obstacle to widespread clinical use. Approaches are needed that exploit the efficacy of the agonist approach but avoid the abuse potential associated with dopamine releasers. ⋯ Tolerance developed to initial decreases in food-maintained responding in the third monkey and in the fourth subject, fluctuations were observed that were lower in magnitude than effects on cocaine self-administration. Cocaine dose-effect curves were shifted down and/or rightward in three monkeys. These data provide further support for the use of agonist medications for cocaine abuse, and indicate that the promising effects of d-amphetamine extend to a more clinically viable pharmacotherapy.