Neuroscience
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Parthanatos is a modality of regulated cell death initiated by poly(ADP-ribose) polymerase 1 (PARP-1) hyperactivation and characterized by apoptosis inducing factor (AIF)-dependent and microphage migration inhibitory factor (MIF)-dependent DNA degradation. It is a caspase-independent, mitochondrial-linked paradigm of cell death and has been demonstrated to be related to the pathogenesis of various nervous system diseases. An in-depth understanding of the role that parthanatos plays in the pathological processes of these diseases can provide new targets for nervous system diseases treatments. In this review, on the basis of parthanatos mechanism, the involvement of parthanatos in the pathogenesis of nervous system diseases including neurodegenerative disorders, cerebrovascular diseases, spinal cord injury and glioma will be summarized in detail.
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Low-power and high-frequency bidirectional control of spatiotemporal patterns of neural spiking is one of the major challenges in optogenetics. A detailed theoretical analysis and optimization with ChR2-NpHR, ChR2(H134R)-eNpHR3.0, Chrimson-GtACR2 and also with prospective opsin pairs namely, Chronos-Jaws, Chronos-eNpHR3.0, CheRiff-Jaws and vf-Chrimson-GtACR2 has been presented. Biophysical circuit models of bidirectional optogenetic control in above opsin pairs expressing hippocampal neurons and fast-spiking neocortical interneurons have been formulated. ⋯ Although, Chrimson-GtACR2 enables bidirectional control at very low-power, vf-Chrimson-GtACR2 provides control with reduced cross-talk. The theoretical analysis highlights the usefulness of computational methods to virtually optimize stimulation protocols for optogenetic tool combinations. The study is useful to generate neural codes with desired spatiotemporal resolution and to design optogenetic neuroprosthetic devices and circuits.
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Dendrite-targeting somatostatin-expressing interneurons (SST-INs) powerfully control signal integration and synaptic plasticity in pyramidal dendrites during cortical development. We previously showed that synaptic transmission from SST-INs to pyramidal cells (PCs) (SST-IN → PC) in the mouse visual cortex suddenly declined at around the second postnatal week. However, it is unclear what specific postsynaptic mechanisms underlie this developmental change. ⋯ Apart from pharmacological test, we observed that SST-IN → PC synapses did indeed contain α5-GABAARs by immunogold labeling for electron microscopy. More importantly, coinciding with the weakening of SST-IN → PC synaptic transmission, the number of α5-GABAAR particles in SST-IN → PC synapses significantly decreased at around the second postnatal week. Together, these data indicate that α5-GABAARs are involved in synaptic transmission from SST-INs to PCs in the neocortex, and are significantly diminished around the second postnatal week.
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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.