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Contrary to our previous work using the same model, here we found that access to alcohol increased cocaine intake and increased responding during early extinction training. We found that as in our previous work, cocaine + alcohol-consuming rats displayed basal glutamate levels below those of rats that self-administered only cocaine. During the cocaine-primed reinstatement test, rats that consumed only cocaine displayed increased glutamate efflux in the NA core while those that consumed cocaine + alcohol did not. These results indicate that preclinical models of PSU should be utilized to develop experimental therapeutics for the reduction of cocaine seeking.Neurodegenerative diseases are characterized by chronic neuronal and/or glial cell loss, while traumatic injury is often accompanied by the acute loss of both. Multipotent neural stem cells (NSCs) in the adult mammalian brain spontaneously proliferate, forming neuronal and glial progenitors that migrate toward lesion sites upon injury. However, they fail to replace neurons and glial cells due to molecular inhibition and the lack of pro-regenerative cues. A major challenge in regenerative biology therefore is to unveil signaling pathways that could override molecular brakes and boost endogenous repair. In physiological conditions, thyroid hormone (TH) acts on NSC commitment in the subventricular zone, and the subgranular zone, the two largest NSC niches in mammals, including humans. Here, we discuss whether TH could have beneficial actions in various pathological contexts too, by evaluating recent data obtained in mammalian models of multiple sclerosis (MS; loss of oligodendroglial cells), Alzheimer's disease (loss of neuronal cells), stroke and spinal cord injury (neuroglial cell loss). So far, TH has shown promising effects as a stimulator of remyelination in MS models, while its role in NSC-mediated repair in other diseases remains elusive. Disentangling the spatiotemporal aspects of the injury-driven repair response as well as the molecular and cellular mechanisms by which TH acts, could unveil new ways to further exploit its pro-regenerative potential, while TH (ant)agonists with cell type-specific action could provide safer and more target-directed approaches that translate easier to clinical settings.Alzheimer's disease (AD), a chronic multifactorial and complex neurodegenerative disorder is a leading cause of dementia. Recently, neuroinflammation has been hypothesized as a contributing factor to AD pathogenesis. The role of adaptive immune responses against neuronal antigens, which can either confer protection or induce damage in AD, has not been fully characterized. Here, we measured T cell responses to several potential antigens of neural origin including amyloid precursor protein (APP), amyloid beta (Aβ), tau, α-synuclein, and transactive response DNA binding protein (TDP-43) in patients with AD and age-matched healthy controls (HC). Antigen-specific T cell reactivity was detected for all tested antigens, and response to tau-derived epitopes was particularly strong, but no significant differences between individuals with AD and age-matched HC were identified. We also did not observe any correlation between the antigen-specific T cell responses and clinical variables including age, gender, years since diagnosis and cognitive score. Additionally, further characterization did not reveal any differences in the relative frequency of major Peripheral Blood Mononuclear Cells (PBMC) subsets, or in the expression of genes between AD patients and HC. These observations have not identified a key role of neuronal antigen-specific T cell responses in AD.Idiopathic restless legs syndrome (RLS) is a sensorimotor disorder and is suggested to be caused by central nervous system abnormalities. Non-invasive transcutaneous spinal direct-current stimulation (tsDCS) was recently used for RLS therapy. However, the neurophysiological basis of tsDCS treatment is still unknown. In this study, we explored the neural basis of tsDCS in 15 RLS patients and 20 gender- and age-matched healthy controls using resting-state functional magnetic resonance imaging. We calculated the whole-brain voxel-wise fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and weighted degree centrality (DC) to characterize the intrinsic functional activities and the local and global functional integration. We found that tsDCS can effectively improve the sleep and RLS symptoms in RLS patients. Moreover, after tsDCS therapy, the RLS patients showed decreased fALFF in the right anterior insula/temporal pole, decreased ReHo in the supplementary motor area, increased weighted DC in the left primary visual cortex, and decreased weighted DC in the right posterior cerebellum. The changed patterns were consistent with that found between RLS patients and healthy controls. The weighted DC in the left primary visual cortex after treatment and the fALFF in the right anterior insula/temporal pole before treatment were significantly and marginally correlated with sleep and RLS symptom scores, respectively. These results revealed that tsDCS can normalize the functional patterns of RLS patients and is an effective way for RLS therapy. [https://www.selleckchem.com/products/durvalumab.html Durvalumab purchase] Our findings provide the neurophysiological basis for tsDCS treatment and may facilitate understanding the neuropathology of RLS and directing other neuromodulation treatments.The perception of speed is influenced by visual contrast. In primary visual cortex (V1), an early stage in the visual perception pathway, the neural tuning to speed is directly related to the neural tuning to temporal frequency of stimulus changes. The influence of contrast on speed perception can be caused by the joint dependency of neural responses in V1 on temporal frequency and contrast. Here, we investigated how tuning to contrast and temporal frequency in V1 of anesthetized mice are related. We found that temporal frequency tuning is contrast-dependent. V1 was more responsive at lower temporal frequencies than the dLGN, consistent with previous work at high contrast. The temporal frequency tuning moves toward higher temporal frequencies with increasing contrast. The low half-maximum temporal frequency does not change with contrast. The Heeger divisive normalization equation provides a good fit to many response characteristics in V1, but does not fit the dependency of temporal frequency and contrast with set of parameters for all temporal frequencies.