Neuroscience
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Acute itch is elicited by histamine, as well as non-histaminergic itch mediators including chloroquine, BAM8-22 and Ser-Leu-Ile-Gly-Arg-Leu (SLIGRL). When injected intradermally, histamine binds to histamine H1 and H4 receptors that activate transient receptor potential vanilloid 1 (TRPV1) to depolarize pruriceptors. Chloroquine, BAM8-22, and SLIGRL, respectively, bind to Mas-related G-protein-coupled receptors MrgprA3, MrgprC11, and MrgprC11/PAR2 that in turn activate transient receptor potential ankyrin 1 (TRPA1). ⋯ Pretreatment with the TRPV1 antagonist AMG-517 (10 or 20 μg), but not the TRPA1 antagonist HC-030031 (50 or 100 μg), significantly attenuated the magnitude and time course of thermal hyperalgesia and mechanical allodynia elicited by histamine (p < 0.001 for both), indicating that these effects are mediated by TRPV1. In contrast, pretreatment with the TRPA1 antagonist significantly reduced thermal hyperalgesia and mechanical allodynia elicited by chloroquine (p < 0.001 for both ), BAM-822 (p < 0.01, p < 0.001, respectively) and SLGRL (p < 0.05, p < 0.001, respectively), indicating that effects elicited by these non-histaminergic itch mediators require TRPA1. TRPV1 and TRPA1 channel inhibitors thus may have potential use in reducing hyperalgesia and allodynia associated with histaminergic and non-histaminergic itch, respectively.
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Randomized Controlled Trial
Failure to Improve Verbal Fluency with Transcranial Direct Current Stimulation.
Previous studies in healthy populations have provided equivocal evidence whether the application of anodal transcranial direct current stimulation (tDCS) over the left prefrontal cortex (PFC) can improve performance in verbal fluency tasks. In this double-blind, randomised within-participant study, we investigated whether anodal tDCS over the left PFC improves verbal fluency performance relative to sham tDCS. Forty eight healthy native German speakers performed two verbal fluency tasks after having received 20 min of anodal or sham tDCS over the left PFC. ⋯ Overall, the current study found no evidence that verbal fluency performance in healthy speakers could be improved by excitatory stimulation of the left PFC. We argue that previously observed positive effects could be false positives and should be interpreted with caution. The findings from the current study thus cast further doubt on the utility of tDCS in enhancing cognitive performance in the healthy (young) brain.
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This is the first study to examine the influence of activity in one limb on corticospinal excitability to the contralateral limb during a locomotor output. Corticospinal and spinal excitability to the biceps brachii of the ipsilateral arm were assessed using transcranial magnetic stimulation (TMS) of the motor cortex and transmastoid electrical stimulation (TMES) of corticospinal axons, respectively. Responses were evoked during the mid-elbow extension position of arm cycling across three different cycling tasks: (1) bilateral arm cycling (BL), (2) unilateral, contralateral cycling with the ipsilateral arm moving passively (IP), and (3) unilateral, contralateral cycling with the ipsilateral arm at rest (IR). ⋯ TMES-evoked cervicomedullary MEP (CMEPs) amplitudes followed a similar pattern of task-dependent modulation, with BL having the smallest CMEPs and IR having the largest. In line with our previous findings, MEP amplitudes increased and CMEP amplitudes decreased as the cadence increased from 60 to 90 rpm. We suggest that the higher corticospinal excitability to the ipsilateral limb during the IP and IR conditions was predominantly due to disinhibition at both the cortical and spinal levels.
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K369I tau mice demonstrate a shift towards striatal neuron burst firing and goal-directed behaviour.
Pathological forms of the microtubule-associated protein tau are involved in a large group of neurodegenerative diseases named tauopathies, including frontotemporal lobar degeneration (FTLD-tau). K369I mutant tau transgenic mice (K3 mice) recapitulate neural and behavioural symptoms of FTLD, including tau aggregates in the cortex, alterations to nigrostriatum, memory deficits and parkinsonism. The aim of this study was to further characterise the K3 mouse model by examining functional alterations to the striatum. ⋯ The observed pattern of behaviour in K3 mice is suggestive of deficits in dorsal lateral striatal function and this was supported by our electrophysiological findings. Thus, both the electrophysiological and behavioural alterations indicate that K3 mice have early deficits in striatal function. This finding adds to the growing literature which indicate that the striatum is impacted in tau-related neuropathies such as FTLD, and further suggests that the K3 model is a unique mouse model for investigating FTLD especially with striatal involvement.
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Dopamine loss in Parkinson's disease (PD) is associated with abnormal oscillatory activity in the cortico-basal ganglia network. However, the oscillatory pattern of striatal neurons in PD remains poorly defined. Here, we analyzed the local field potentials in one untreated and five MPTP-treated non-human primates (NHP) with chronic, advanced parkinsonism. ⋯ Both alpha and low-beta frequency band oscillations of the striatum were highly coherent with the cortical and pallidal oscillations, confirming the presence of abnormal 8-20 Hz oscillatory activity in the cortico-basal ganglia network in parkinsonian NHPs. The reversal of parkinsonism induced by acute levodopa administration was associated with reduced 8-20 Hz oscillations in the striatum. These findings indicate that pathological oscillations at alpha and low-beta bands are also present in the striatum concordant with basal ganglia network changes in the primate model of PD.