Carneyreynolds1447

Sprouting of surviving axons is one of the major reorganization mechanisms of the injured brain contributing to a partial restoration of function. Of note, sprouting is maturation as well as age-dependent and strong in juvenile brains, moderate in adult and weak in aged brains. We have established a model system of complex organotypic tissue cultures to study sprouting in the dentate gyrus following entorhinal denervation. Entorhinal denervation performed after 2 weeks postnatally resulted in a robust, rapid, and very extensive sprouting response of commissural/associational fibers, which could be visualized using calretinin as an axonal marker. In the present study, we analyzed the effect of maturation on this form of sprouting and compared cultures denervated at 2 weeks postnatally with cultures denervated at 4 weeks postnatally. Calretinin immunofluorescence labeling as well as time-lapse imaging of virally-labeled (AAV2-hSyn1-GFP) commissural axons was employed to study the sprouting response in aged cultures. Compared to the young cultures commissural/associational sprouting was attenuated and showed a pattern similar to the one following entorhinal denervation in adult animals in vivo. We conclude that a maturation-dependent attenuation of sprouting occurs also in vitro, which now offers the chance to study, understand and influence maturation-dependent differences in brain repair in these culture preparations.Urea transporter B (UT-B) is a membrane channel protein widely distributed in mammals, and plays a significant physiological role by regulating urea and water transportation in different tissues. More and more studies have found that UT-B is related to neurological diseases, including myelinopathy and depression. When urea accumulates in the brains of UT-B knockout mice, the synaptic plasticity of neurons is reduced, and the morphology and function of glial cells are also changed. However, the distribution and expression change of UT-B remain unclear. The purpose of this study is to determine the expression characteristics of UT-B in the brain. Through single-cell RNA sequencing, UT-B was found to express universally and substantially throughout the various cells in the central nervous system except for endothelial and smooth muscle cells. UT-B was detected in the third cerebral ventricular wall, granule cell layer of the dentate gyrus, and other parts of the hippocampal, cerebral cortex, substantia nigra, habenular, and lateral hypothalamic nucleus by immunohistochemistry. Compared with the membrane expression of UT-B in glial cells, the subcellular localization of UT-B is in the Golgi apparatus of neurons. Further, the expression of UT-B was regulated by osmotic pressure in vitro. In the experimental traumatic brain injury model (TBI), the number of UT-B positive neurons near the ipsilateral cerebral cortex increased first and then decreased over time, peaking at the 24 h. We inferred that change in UT-B expression after the TBI was an adaptation to changed urea levels. The experimental data suggest that the UT-B may be a potential target for the treatment of TBI and white matter edema.The corticostriatal circuit has been identified as a vital pathway for associative learning. However, how learning is implemented when the sensory striatum is permanently impaired remains unclear. Using chemogenetic techniques to suppress layer five auditory cortex (AC) input to the auditory striatum, learning of a sound discrimination task was significantly impacted in freely moving Mongolian gerbils, in particular when this suppression occurs early on during learning. Whole-cell recordings sampled throughout learning revealed a transient reduction in postsynaptic (GABAA) inhibition in both striatal D1 and D2 cells in normal-hearing gerbils during task acquisition. www.selleckchem.com/CDK.html In contrast, when the baseline striatal inhibitory strengths and firing rates were permanently reduced by a transient period of developmental sensory deprivation, learning was accompanied by augmented inhibition and increased firing rates. Direct manipulation of striatal inhibition in vivo and in vitro revealed a key role of the transient inhibitory changes in task acquisition. Together, these results reveal a flexible corticostriatal inhibitory synaptic plasticity mechanism that accompanies associative auditory learning.Parvalbumin-expressing (PV+) interneurons are a subset of GABAergic inhibitory interneurons that mediate feed-forward inhibition (FFI) within the cortico-thalamocortical (CTC) network of the brain. The CTC network is a reciprocal loop with connections between cortex and thalamus. FFI PV+ interneurons control the firing of principal excitatory neurons within the CTC network and prevent runaway excitation. Studies have shown that generalized spike-wave discharges (SWDs), the hallmark of absence seizures on electroencephalogram (EEG), originate within the CTC network. In the stargazer mouse model of absence epilepsy, reduced FFI is believed to contribute to absence seizure genesis as there is a specific loss of excitatory α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at synaptic inputs to PV+ interneurons within the CTC network. However, the degree to which this deficit is directly related to seizure generation has not yet been established. Using chemogenetics and in vivo EEG recording,O activation of FFI either prevented PTZ-induced absence seizures or suppressed their severity. Furthermore, PTZ-induced tonic-clonic seizures were also reduced in severity by activation of FFI PV+ interneurons. In contrast, administration of CNO to non-DREADD wild-type control animals did not afford any protection against PTZ-induced seizures. These data demonstrate that FFI PV+ interneurons within CTC microcircuits could be a potential therapeutic target for anti-absence seizure treatment in some patients.[This corrects the article DOI 10.3389/fncel.2019.00435.].Voltage imaging and "all-optical electrophysiology" in human induced pluripotent stem cell (hiPSC)-derived neurons have opened unprecedented opportunities for high-throughput phenotyping of activity in neurons possessing unique genetic backgrounds of individual patients. While prior all-optical electrophysiology studies relied on genetically encoded voltage indicators, here, we demonstrate an alternative protocol using a synthetic voltage sensor and genetically encoded optogenetic actuator that generate robust and reproducible results. We demonstrate the functionality of this method by measuring spontaneous and evoked activity in three independent hiPSC-derived neuronal cell lines with distinct genetic backgrounds.