The function of dendritic spines, postsynaptic sites excitatory input in the mammalian central nervous system (CNS), is still not well understood. Although changes spine morphology may mediate synaptic plasticity, extent basal motility and its regulation remains controversial. We investigated three principal neurons mouse CNS: cerebellar Purkinje cells, cortical hippocampal pyramidal neurons. Motility was assayed with time-lapse imaging by using two-photon microscopy green fluorescent...

The process of oligodendrogenesis has been relatively well delineated in the rodent brain. However, it remains unknown whether analogous developmental processes are manifested human Here we report forebrain organoids, generated by using OLIG2-GFP knockin pluripotent stem cell (hPSC) reporter lines. OLIG2/GFP exhibits distinct temporal expression patterns ventral organoids (VFOs) versus dorsal (DFOs). Interestingly, can be induced both VFOs and DFOs after neuronal maturation. Assembling to...

Both genetic and environmental factors are thought to contribute neurodevelopmental neuropsychiatric disorders with maternal immune activation (MIA) being a risk factor for both autism spectrum schizophrenia. Although MIA mouse offspring exhibit behavioral impairments, the synaptic alterations in vivo that mediate these behaviors not known. Here we employed multiphoton imaging determine cortex of young there is reduction number turnover rates dendritic spines, sites majority excitatory...

Activity-dependent synaptic plasticity is likely to provide a mechanism for learning and memory. Cortical responses that are strengthened within fixed modification range after 5 days of motor skill driven near the top their range, leaving only limited room additional strengthening. If strengthening requisite step acquiring new skills, saturation long-term potentiation (LTP) should impede further or LTP recover single-task learning. Here we show initial learning-induced enhancement sustained...

Fragile X syndrome (FXS) is the most common inherited intellectual disability. FXS results from a mutation that causes silencing of FMR1 gene, which encodes fragile mental retardation protein. Patients with exhibit range neurological deficits, including motor skill deficits. Here, we have investigated learning and its synaptic correlates in fmr1 knock-out (KO) mouse. We find KO mice impaired forelimb-reaching task, compared their wild-type (WT) littermate controls. Electrophysiological...

Emerging epidemiology studies indicate that maternal immune activation (MIA) resulting from inflammatory stimuli such as viral or bacterial infections during pregnancy serves a risk factor for multiple neurodevelopmental disorders including autism spectrum and schizophrenia. Although alterations in the cortex hippocampus of MIA offspring have been described, less evidence exists on impact cerebellum. Here, we report altered expression cytokines chemokines cerebellum offspring, increase...

Experience-dependent regulation of synaptic strength in the horizontal connections layer 1 primary motor cortex is likely to play an important role learning. Dendritic spines, sites excitatory synapses brain, are known change shape response various experimental stimuli. We used a rat learning model examine connection via field recordings slices and confocal imaging labeled spines explore changes induced solely by simple task. report that increases size, while transiently occluding long-term...

Abstract The pattern of growth Purkinje cell dendrites has been analyzed and related to their interactions with Bergmann glial radial processes. In cerebellar slice cultures from mice expressing green fluorescent protein (GFP) under the fibrillary acidic (GFAP) promoter, cells were transfected imaged two‐photon microscopy over 2 days. We report that while dendritic tree grows, individual increase or decrease in length. Importantly, we demonstrate vertical occurs primarily alignment These...

Abstract Astrocytes have an important role in synaptic formation and function but how astrocytic processes become associated with structures during development is not well understood. Here we analyzed the pattern of growth extending off main Bergmann glial (BG) shafts synaptogenesis cerebellum. We found that this period, BG process outgrowth was correlated increased ensheathment dendritic spines. In addition, two‐photon time‐lapse imaging revealed were highly dynamic, became more stable as...

Motor-skill learning induces changes in synaptic structure and function the primary motor cortex through involvement of a long-term potentiation- (LTP-) like mechanism. Although there is evidence that calcium-dependent release gliotransmitters by astrocytes plays an important role transmission plasticity, motor-skill not known. To test hypothesis astrocytic activity necessary for learning, we perturbed using pharmacological genetic approaches. We find perturbation either selectively...

Following traumatic or ischemic brain injury, rapid cell death and extracellular matrix degradation lead to the formation of a cavity at lesion site, which is responsible for prolonged neurological deficits permanent disability. Transplantation neural stem/progenitor cells (NSCs) represents promising strategy reconstructing promoting tissue regeneration. In particular, promotion neuronal migration, organization, integration transplanted NSCs critical success stem cell-based therapy. This...

Abstract Fragile X syndrome (FXS), the most prevalent heritable form of intellectual disability, is caused by transcriptional silencing FMR1 gene. While neuronal contribution to FXS has been extensively studied in both animal and human‐based models FXS, roles astrocytes, a type glial cells brain, are largely unknown. Here, we generated model via differentiation astrocytes from human‐induced pluripotent stem (hiPSCs) human embryonic (hESCs) characterized their development, function, proteomic...

Structural dynamics of dendritic spines are important for memory and learning impaired in neurodevelopmental disorders such as fragile X syndrome. Spine regulated by activity-dependent mechanisms that involve modulation AMPA receptors (AMPAR); however, the relationship between AMPAR spine vivo how these altered FXS mouse model is not known. Here, we tracked over multiple days cortex found fmr1 KO were denser, smaller, had higher turnover rates contained less sGluA2 compared to littermate...

To gain insight into the role of F-actin in organization synaptic vesicles at release sites, we examined distribution by using a unique preparation frog target-deprived nerve terminals. In this preparation, imaging site was unobstructed muscle fiber cytoskeleton, allowing for examination hundreds sites their entirety whole mounts. At distributed ladder-like pattern and colocalized with β-fodrin. Surprisingly, stain, which localized to terminal itself, did not overlap vesicle marker,...

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and a leading cause autism spectrum disorder (ASD). FXS caused by mutations in fragile messenger ribonucleoprotein gene 1 (FMR1), which result complete or partial loss expression its protein product, (FMRP). Neuronal impairments absence FMRP have been extensively characterized. However, much less known about impact that has on physiology function astrocytes implications for behavior. A behavior exhibited...

Astrocytes, a type of glial cells, have multiple roles in regulating neuronal development and homeostasis. In addition to the typical mammalian astrocytes, primate cortex interlaminar astrocytes are located superficial layer project long processes traversing layers cerebral cortex. Previously, we described human stem cell based chimeric mouse model where develop. Here, utilized this study calcium signaling properties astrocytes. To determine how could contribute neurodevelopmental disorders,...

In the cerebellum, lamellar Bergmann glial (BG) appendages wrap tightly around almost every Purkinje cell dendritic spine. The function of this ensheathment spines is not entirely understood. development begins near onset synaptogenesis, when motility both BG processes and are high. By end synaptogenic period, complete decreases, correlating with decreased spines. We therefore have hypothesized that intimately involved in capping possibly by stabilizing synapses. To test hypothesis, we...