The Adult Astrocyte Is Different concept of the tripartite synapse, whereby astrocytes actively modulate communication between pre- and postsynaptic site, is widely accepted. release gliotransmitters has been linked to Ca 2÷ from intracellular stores via activation astrocytic metabotropic glutamate receptor 5 (mGluR5) by spillover synapses. However, nearly all studies on synapse have used brain tissue collected young individuals. Many receptors undergo changes in expression level during...

The alpha1-fetoprotein (AFP) gene is located between the albumin and alpha-albumin genes activated by transcription factor FTF (fetoprotein factor), presumed to transduce early developmental signals cluster. We have identified as an orphan nuclear receptor of Drosophila FTZ-F1 family. recognizes DNA sequence 5'-TCAAGGTCA-3', canonical recognition motif for receptors. cDNA homologies indicate that rat ortholog mouse LRH-1 Xenopus xFF1rA. Rodent encoded a single-copy gene, related encoding...

Abstract An enigmatic feature of age‐related neurodegenerative diseases is that they seldom, if ever, are fully manifested in nonhuman species under natural conditions. The tauopathies typified by the intracellular aggregation hyperphosphorylated microtubule‐associated protein tau (MAPT) and dysfunction death affected neurons. We document first case tauopathy with paired helical filaments an aged chimpanzee ( Pan troglodytes ). Pathologic forms neuronal somata, neuropil threads, plaque‐like...

Key points Xenopus laevis craniofacial development is a good system for the study of Andersen–Tawil Syndrome (ATS)‐associated anomalies (CFAs) because (1) Kcnj2 expressed in nascent face; (2) molecular‐genetic and biophysical techniques are available ion‐dependent signalling during morphogenesis; (3) as humans, expression variant forms embryos causes muscle phenotype; (4) found human patients, when injected into frog embryos, cause CFAs same cell lineages. Forced WT or changes normal pattern...

Biophysical forces play important roles throughout embryogenesis, but the of spatial differences in cellular resting potentials during large-scale brain morphogenesis remain unknown. Here, we implicate endogenous bioelectricity as an instructive factor patterning Xenopus laevis . Early frog embryos exhibit a characteristic hyperpolarization cells lining neural tube; disruption this gradient transmembrane potential ( V mem ) diminishes or eliminates expression early markers, and causes...

The fetoprotein transcription factor (FTF) gene was inactivated in the mouse, with a lacZ inserted inframe into exon 4. LacZ staining of FTF+/- embryos shows that mFTF is activated at initial stages zygotic transcription. FTF activity ubiquitous morula and blastocyst then follows expression patterns indicative multiple functions fetal development. FTF-/- die E6.5–7.5, features typical visceral endoderm dysfunction. Adult mice are hypocholesterolemic, express liver about 40% normal level....

Abstract In the hippocampal formation, Ca v 1.2 (L‐type) voltage‐gated 2+ channels mediate signals that can trigger long‐term alterations in synaptic efficacy underlying learning and memory. Immunocytochemical studies indicate are localized mainly soma proximal dendrites of pyramidal neurons, but electrophysiological data suggest a broader distribution these channels. To define subcellular substrates signals, we analyzed localization formation by using antibodies against pore‐forming α 1...

The striatum and the subthalamic nucleus are main entry points for cortical information to basal ganglia. Parkinson's disease affects not only function, but also morphological integrity of some these inputs their synaptic targets in Significant changes cortico-striatal system have already been recognized patients with animal models disease. To find out whether primate cortico-subthalamic is subject functionally relevant alterations parkinsonism, we used a combination light electron...

The GluN2D subunit of the NMDA receptor is prominently expressed in basal ganglia and associated brainstem nuclei, including subthalamic nucleus (STN), globus pallidus, striatum, substantia nigra. However, little known about how GluN2D-containing receptors contribute to synaptic activity these regions. Using Western blotting STN tissue punches, we demonstrated that rat throughout development [age postnatal day 7 (P7)–P60] adult (age P120). Immunoelectron microscopy brain showed predominantly...

Treatment for higher-risk non-muscle invasive bladder cancer (NMIBC) involves intravesical immunotherapy with Bacillus Calmette Guérin (BCG); however, disease recurrence and progression occur frequently. Systemic immunity is critical successful immunotherapy; thus, of NMIBC may be due to suboptimal systemic activation anti-tumor after local immunotherapy. We previously reported that systemically acquired trained (a form innate immune memory) in circulating monocytes associated increased...

Abstract In primates, thalamostriatal projections from the centromedian (CM) and parafascicular (Pf) nuclei are strong organized according to a strict pattern of functional connectivity with various regions striatal complex. turn, CM/Pf complex receives substantial innervation internal globus pallidus (GPi). this study, we demonstrate that substantia nigra pars reticulata (SNr) also provides massive input Pf in monkeys. These pallidothalamic nigrothalamic provide routes whereby information...

Dysbindin assembles into the biogenesis of lysosome-related organelles complex 1 (BLOC-1), which interacts with adaptor protein 3 (AP-3), mediating a common endosome-trafficking route. Deficiencies in AP-3 and BLOC-1 affect synaptic vesicle composition. However, whether AP-3-BLOC-1–dependent sorting events that control synapse membrane content take place cell bodies upstream nerve terminals remains unknown. We tested this hypothesis by analyzing targeting phosphatidylinositol-4-kinase type...

Striatal cholinergic interneurons (ChIs) are involved in reward-dependent learning and the regulation of attention. The activity these neurons is modulated by intrinsic extrinsic γ-aminobutyric acid (GABA)ergic glutamatergic afferents, but source relative prevalence diverse regulatory inputs remain to be characterized. To address this issue, we performed a quantitative ultrastructural analysis GABAergic innervation ChIs postcommissural putamen rhesus monkeys. Postembedding immunogold...

Abnormal dopamine neurotransmission is associated with many different genetic and acquired dystonic disorders. For instance, mutations in genes critical for the synthesis of dopamine, including GCH1 TH cause l-DOPA-responsive dystonia. Despite evidence that implicates abnormal dystonia, precise nature pre- postsynaptic defects result dystonia are not known. To better understand these defects, we generated a knock-in mouse model (DRD) mice recapitulates human p.381Q>K mutation (c.1141C>A)....

Abstract Designer receptors exclusively activated by designer drugs ( DREADD s) are extensively used to modulate neuronal activity in rodents, but their use primates remains limited. An essential need that is the demonstration s efficiently expressed on plasma membrane of primate neurons. To address this issue, electron microscopy immunogold was determine subcellular localization AAV vector‐induced hM 4Di and 3Dq fused different tags various brain areas rhesus monkeys mice. When mC herry,...

ABSTRACT Glutamate delta receptor 1 (GluD1) is a unique synaptogenic molecule expressed at excitatory and inhibitory synapses. The lateral habenula (LHb), subcortical structure that regulates negative reward prediction error major monoaminergic systems, enriched in GluD1. LHb dysfunction has been implicated psychiatric disorders such as depression schizophrenia, both of which are associated with GRID1 , the gene encodes Thus, disruption GluD1 synaptic signaling may contribute to...

Endosomal sorting mechanisms mediated by AP-3 and BLOC-1 are perturbed in Hermansky-Pudlak Syndrome, a human genetic condition characterized albinism prolonged bleeding (OMIM #203300). Additionally, mouse models defective either one of these complexes possess synaptic vesicle biogenesis (Newell-Litwa et al., 2009). These phenotypes were presumed uniform throughout the brain. However, here we report that differentially regulate composition presynaptic terminals striatum dentate gyrus...

The subthalamic nucleus (STN) receives a dopaminergic innervation from the substantia nigra pars compacta, but role of this projection remains poorly understood, particularly in primates. To address issue, we used immuno-electron microscopy to localize D1, D2, and D5 dopamine receptors STN rhesus macaques studied electrophysiological effects activating D1-like or D2-like normal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated parkinsonian monkeys. Labeling D1 D2 was primarily...

Abstract NR5A2, also known as liver receptor homologue 1 (LRH‐1) and fetoprotein transcription factor (FTF), is an orphan nuclear involved in the regulation of cholesterol metabolism steroidogenesis adult. NR5A2 was shown to be expressed during early mouse embryogenesis. Consistent with its expression pattern, a targeted disruption this gene leads embryonic lethality around gastrulation period. To characterize phenotype resulting from loss function, we undertook morphological marker analyses...