Invaginating Structures in Synapses - Perspective.

Invaginating structures are common in the synapses of most animals. However, the details of these invaginating structures remain understudied in part because they are not well resolved in light microscopy and were often misidentified in early electron microscope (EM) studies. Utilizing experimental techniques along with the latest advances in microscopy, such as focused ion beam-scanning EM (FIB-SEM), evidence is gradually building to suggest that the synaptic invaginating structures contribute to synapse development, maintenance, and plasticity.

HPV32-related Heck's disease in a chronic graft-versus-host disease patient with long-term successful KTP laser treatment: A rare case report.

We recently identified and treated a rare case of oral focal epithelial hyperplasia (FEH) in an adult patient with chronic graft-vs-host disease. This is the first report linking KTP laser therapy to successful long-term treatment HPV32 FEH.

Surgical Methods for Inner Ear Gene Delivery in Neonatal Mouse.

Inner ear gene therapy offers great potential as a treatment for hearing loss and dizziness. The surgical method used to deliver gene therapy into the inner ear is a critical step in determining the success of inner ear gene therapy. Here we describe two commonly used surgical methods for gene delivery in neonatal mouse inner ear: the round window approach and the posterior semicircular canal approach.

Enlargement of Ribbons in Zebrafish Hair Cells Increases Calcium Currents But Disrupts Afferent Spontaneous Activity and Timing of Stimulus Onset.

In sensory hair cells of auditory and vestibular organs, the ribbon synapse is required for the precise encoding of a wide range of complex stimuli. Hair cells have a unique presynaptic structure, the synaptic ribbon, which organizes both synaptic vesicles and calcium channels at the active zone. Previous work has shown that hair-cell ribbon size is correlated with differences in postsynaptic activity.

Syngap1 haploinsufficiency damages a postnatal critical period of pyramidal cell structural maturation linked to cortical circuit assembly.

Background: Genetic haploinsufficiency of SYNGAP1/Syngap1 commonly occurs in developmental brain disorders, such as intellectual disability, epilepsy, schizophrenia, and autism spectrum disorder. Thus, studying mouse models of Syngap1 haploinsufficiency may uncover pathologic developmental processes common among distinct brain disorders.

Methods: A Syngap1 haploinsufficiency model was used to explore the relationship between critical period dendritic spine abnormalities, cortical circuit assembly, and the window for genetic rescue to understand how damaging mutations disrupt key substrates of mouse brain development.

Segregating neural and mechanosensory fates in the developing ear: patterning, signaling, and transcriptional control.

The vertebrate inner ear is composed of multiple sensory receptor epithelia, each of which is specialized for detection of sound, gravity, or angular acceleration. Each receptor epithelium contains mechanosensitive hair cells, which are connected to the brainstem by bipolar sensory neurons. Hair cells and their associated neurons are derived from the embryonic rudiment of the inner ear epithelium, but the precise spatial and temporal patterns of their generation, as well as the signals that coordinate these events, have only recently begun to be understood.

MAGUKs, synaptic development, and synaptic plasticity.

MAGUKs are proteins that act as key scaffolds in surface complexes containing receptors, adhesion proteins, and various signaling molecules. These complexes evolved prior to the appearance of multicellular animals and play key roles in cell-cell intercommunication. A major example of this is the neuronal synapse, which contains several presynaptic and postsynaptic MAGUKs including PSD-95, SAP102, SAP97, PSD-93, CASK, and MAGIs.

Hierarchical auditory processing directed rostrally along the monkey's supratemporal plane.

Connectional anatomical evidence suggests that the auditory core, containing the tonotopic areas A1, R, and RT, constitutes the first stage of auditory cortical processing, with feedforward projections from core outward, first to the surrounding auditory belt and then to the parabelt. Connectional evidence also raises the possibility that the core itself is serially organized, with feedforward projections from A1 to R and with additional projections, although of unknown feed direction, from R to RT. We hypothesized that area RT together with more rostral parts of the supratemporal plane (rSTP) form the anterior extension of a rostrally directed stimulus quality processing stream originating in the auditory core area A1.

Organization of NMDA receptors at extrasynaptic locations.

NMDA receptors are found in neurons both at synapses and in extrasynaptic locations. Extrasynaptic locations are poorly characterized. Here we used preembedding immunoperoxidase and postembedding immunogold electron microscopy and fluorescence light microscopy to characterize extrasynaptic NMDA receptor locations in dissociated hippocampal neurons in vitro and in the adult and postnatal hippocampus in vivo.

Neural aspects of sentence comprehension: syntactic complexity, reversibility, and reanalysis.

Broca's area is preferentially activated by reversible sentences with complex syntax, but various linguistic factors may be responsible for this finding, including syntactic movement, working-memory demands, and post hoc reanalysis. To distinguish between these, we tested the interaction of syntactic complexity and semantic reversibility in a functional magnetic resonance imaging study of sentence-picture matching. During auditory comprehension, semantic reversibility induced selective activation throughout the left perisylvian language network.

Gamma-actin is required for cytoskeletal maintenance but not development.

Beta(cyto)-actin and gamma(cyto)-actin are ubiquitous proteins thought to be essential building blocks of the cytoskeleton in all non-muscle cells. Despite this widely held supposition, we show that gamma(cyto)-actin null mice (Actg1(-/-)) are viable. However, they suffer increased mortality and show progressive hearing loss during adulthood despite compensatory up-regulation of beta(cyto)-actin.

The septate junction protein caspr is required for structural support and retention of KCNQ4 at calyceal synapses of vestibular hair cells.

The afferent innervation contacting the type I hair cells of the vestibular sensory epithelia form distinct calyceal synapses. The apposed presynaptic and postsynaptic membranes at this large area of synaptic contact are kept at a remarkably regular distance. Here, we show by freeze-fracture electron microscopy that a patterned alignment of proteins at the calyceal membrane resembles a type of intercellular junction that is rare in vertebrates, the septate junction (SJ).

Planar and vertical signals control cellular differentiation and patterning in the mammalian cochlea.

The sensory epithelium of the mammalian cochlea is composed of a regular mosaic of sensory hair cells and nonsensory supporting cells. During development, differentiation occurs in a gradient that progresses along the axis of the cochlea from base to apex. To begin to identify some of the factors that regulate this developmental process, the potential roles of planar and vertical signals were examined during early stages of cochlear development.

Glutamate receptor targeting to synaptic populations on Purkinje cells is developmentally regulated.

Selective targeting of neurotransmitter receptors to specific synapse populations occurs in adult neurons, but little is known about the development of these receptor distribution patterns. In this study, we demonstrate that a specific developmental switch occurs in the targeting of a receptor to an identified synapse population. Localization of delta and AMPA glutamate receptors at parallel and climbing fiber synapses on the developing Purkinje cells was studied using postembedding immunogold.

Endbulb synapses in the anteroventral cochlear nucleus express a specific subset of AMPA-type glutamate receptor subunits.

The anteroventral cochlear nucleus (AVCN) acts as the first relay center in the conduction of auditory information from the ear to the brain, and it probably performs a crucial role in sound localization. Auditory nerve input to the principal neurons of the AVCN, the spherical bushy cells, appears to be mediated by an excitatory amino acid such as glutamate, which acts at a specialized, large synaptic ending called an endbulb of Held. Presumably, endbulb synapses contain some specific combination of glutamate receptors to facilitate rapid neurotransmission of auditory signals.

Altered patterns of cerebral activity during speech and language production in developmental stuttering. An H2(15)O positron emission tomography study.

To assess dynamic brain function in adults who had stuttered since childhood, regional cerebral blood flow (rCBF) was measured with H2O and PET during a series of speech and language tasks designed to evoke or attenuate stuttering. Speech samples were acquired simultaneously and quantitatively compared with the PET images. Both hierarchical task contrasts and correlational analyses (rCBF versus weighted measures of dysfluency) were performed.