Fryegriffin5101

Although theta-burst stimulation (TBS) is known to differentially modify motor cortical excitability according to stimulus conditions in humans, whether similar effects can be seen in animals, in particular rats, remains to be defined. Given the importance of experimental rat models for humans, this study explored this stimulation paradigm in rats. Specifically, this study aimed to explore corticospinal excitability after TBS in anesthetized animals to confirm its comparability with human results. Both inhibition-facilitation configurations using paired electrical stimulation protocols and the effects of the TBS paradigm on motor-evoked potentials (MEPs) in rat descending motor pathways were assessed. Paired-stimulation MEPs showed inhibition [interstimulus interval (ISI) 3 ms] and facilitation (11 ms) patterns under medetomidine/midazolam/butorphanol (MMB) anesthesia. Furthermore, while ketamine and xylazine (K/X) anesthesia completely blocked facilitation at 11-ms ISI, inhibition at a 3-ms ISI was preserved. Continuous and intermittent TBS strongly facilitated MEPs depending on stimulus intensity, persisting for up to 25 min under both MMB and K/X anesthesia. These findings are similar to the intracortical inhibition and facilitation observed in the human motor cortex using paired-pulse magnetic stimulation, particularly the glutamate-mediated facilitation phase. Cp2-SO4 However, different TBS facilitatory mechanisms occur in the rat motor cortex. These different TBS facilitatory mechanisms affect the comparability and interpretations of TBS between rat and human models.

Repetitive transcranial magnetic stimulation (rTMS) has been employed for motor function rehabilitation for stroke patients, but its effects on post-stroke cognitive impairment (PSCI) remains controversial.

To identify the effects of rTMS intervention on PSCI patients and its potential neural correlates to behavioral improvements.

We recruited 34 PSCI patients for 20 sessions of 10 Hz rTMS or no-stim control treatments over the left dorsal lateral prefrontal cortex (DLPFC). Cognitive function was evaluated with the Montreal Cognitive Assessment Scale, Victoria Stroop Test, Rivermead Behavior Memory Test, and Activities of Daily Living (ADL) assessed with the Modified Barthel Index. 14 patients received functional MRI scan, a useful non-invasive technique of determining how structurally segregated and functionally specialized brain areas were interconnected, which was reflected by blood oxygenation level-dependent signals. The amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) were applied as the analytical approaches, which were used to measure the resting-state brain activity and functional connection.

rTMS improved cognitive functions and ADLs for PSCI patients relative to patients who received no-stim control treatment. The cognitive improvements correlated to increased ALFF of the left medial prefrontal cortex, and increased FC of right medial prefrontal cortex and right ventral anterior cingulate cortex.

10 Hz rTMS at DLPFC could improve cognitive function and quality of life for PSCI patients, which is associated with an altered frontal cortical activity.

Chinese Clinical Trial Registry, ChiCTR-IPR-17011908, http//www.chictr.org.cn/index.aspx.

Chinese Clinical Trial Registry, ChiCTR-IPR-17011908, http//www.chictr.org.cn/index.aspx.It is commonly assumed that memories about experienced stimuli are represented by groups of highly interconnected neurons called cell assemblies. This requires allocating and storing information in the neural circuitry, which happens through synaptic weight adaptations at different types of synapses. In general, memory allocation is associated with synaptic changes at feed-forward synapses while memory storage is linked with adaptation of recurrent connections. It remains, however, largely unknown how memory allocation and storage can be achieved and the adaption of the different synapses involved be coordinated to allow for a faithful representation of multiple memories without disruptive interference between them. In this theoretical study, by using network simulations and phase space analyses, we show that the interplay between long-term synaptic plasticity and homeostatic synaptic scaling organizes simultaneously the adaptations of feed-forward and recurrent synapses such that a new stimulus forms a new memory and where different stimuli are assigned to distinct cell assemblies. The resulting dynamics can reproduce experimental in-vivo data, focusing on how diverse factors, such as neuronal excitability and network connectivity, influence memory formation. Thus, the here presented model suggests that a few fundamental synaptic mechanisms may suffice to implement memory allocation and storage in neural circuitry.Background Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide and involves deficiencies in alpha-synuclein (α-Syn) degradation. Effective therapeutic strategies for PD are urgently needed. L-asparaginase (L-ASNase) has been developed for therapeutic applications in many fields because it catalyzes the hydrolysis of asparagine and glutamine in cancer cells, which may also activate autophagy and induce the degradation of accumulated α-Syn. However, the efficacy and related mechanism of L-ASNase in PD remain poorly understood. Methods We determined the correlation between L-ASNase and autophagic degradation of α-Syn in a cell model of PD. Mitochondrial function and apoptosis were examined in the presence or absence of L-ASNase. Then, we applied GC-MS/MS targeted amino acid metabolomics analysis to validate the amino acid regulation induced by L-ASNase treatment. Glutamine was added to verify whether the neuroprotective effect was induced by deprivation of glutamine. α-Syn-related autophagy and mitochondrial fusion/fission dynamics were detected to explore the mechanism of L-ASNase-based therapy in PD. Results L-ASNase activated the autophagic degradation of α-Syn in a cell model of PD without cytotoxicity at specific concentrations/times. Under these conditions, L-ASNase showed substantial neuroprotective effects, including improvements in mitochondrial function and decreased apoptosis. Through GC-MS/MS targeted analysis, glutamine metabolism was identified as the target of L-ASNase in PD treatment, and the neuroprotective effect of L-ASNase was reduced after glutamine supplementation. Conclusions Our study demonstrated for the first time that L-ASNase had a neuroprotective effect on a cell model of PD through a moderate deprivation of glutamine, which induced autophagic activation and mitochondrial fusion. Therefore, we demonstrated that L-ASNase could be a promising and effective drug for PD treatment.