Astrocyte ensheathment of calyx-forming axons of the auditory brainstem precedes accelerated expression of myelin genes and myelination by oligodendrocytes.

Early postnatal brain development involves complex interactions among maturing neurons and glial cells that drive tissue organization. We previously analyzed gene expression in tissue from the mouse medial nucleus of the trapezoid body (MNTB) during the first postnatal week to study changes that surround rapid growth of the large calyx of Held (CH) nerve terminal. Here, we present genes that show significant changes in gene expression level during the second postnatal week, a developmental timeframe that brackets the onset of airborne sound stimulation and the early stages of myelination.

Transcriptional profiling reveals roles of intercellular Fgf9 signaling in astrocyte maturation and synaptic refinement during brainstem development.

Neural tissue maturation is a coordinated process under tight transcriptional control. We previously analyzed the kinetics of gene expression in the medial nucleus of the trapezoid body (MNTB) in the brainstem during the critical postnatal phase of its development. While this work revealed timed execution of transcriptional programs, it was blind to the specific cells where gene expression changes occurred.

Contribution of HCN1 variant to sinus bradycardia: A case report.

Background: Missense mutations in the hyperpolarization-activated cyclic nucleotide-modulated (HCN) channel 4 (HCN4) are one of the genetic causes of cardiac sinus bradycardia.

Objective: To investigate possible HCN4 channel mutation in a young patient with profound sinus bradycardia.

Methods: Direct sequencing of and whole-exome sequencing were performed on DNA samples from the indexed patient (P), the patient's son (PS), and a family unrelated healthy long-distance running volunteer (V).

Mutations in ARL2BP, a protein required for ciliary microtubule structure, cause syndromic male infertility in humans and mice.

Cilia are evolutionarily conserved hair-like structures with a wide spectrum of key biological roles, and their dysfunction has been linked to a growing class of genetic disorders, known collectively as ciliopathies. Many strides have been made towards deciphering the molecular causes for these diseases, which have in turn expanded the understanding of cilia and their functional roles. One recently-identified ciliary gene is ARL2BP, encoding the ADP-Ribosylation Factor Like 2 Binding Protein.

Glial Cell Expansion Coincides with Neural Circuit Formation in the Developing Auditory Brainstem.

Neural circuit formation involves maturation of neuronal, glial and vascular cells, as well as cell proliferation and cell death. A fundamental understanding of cellular mechanisms is enhanced by quantification of cell types during key events in synapse formation and pruning and possessing qualified genetic tools for cell type-specific manipulation. Acquiring this information in turn requires validated cell markers and genetic tools.

Embryonic markers of cone differentiation.

Purpose: Photoreceptor cells are born in two distinct phases of vertebrate retinogenesis. In the mouse retina, cones are born primarily during embryogenesis, while rod formation occurs later in embryogenesis and early postnatal ages. Despite this dichotomy in photoreceptor birthdates, the visual pigments and phototransduction machinery are not reactive to visual stimulus in either type of photoreceptor cell until the second postnatal week.

Temporal patterns of gene expression during calyx of held development.

Relating changes in gene expression to discrete developmental events remains an elusive challenge in neuroscience, in part because most neural territories are comprised of multiple cell types that mature over extended periods of time. The medial nucleus of the trapezoid body (MNTB) is an attractive vertebrate model system that contains a nearly homogeneous population of neurons, which are innervated by large glutamatergic nerve terminals called calyces of Held (CH). Key steps in maturation of CHs and MNTB neurons, including CH growth and competition, occur very quickly for most cells between postnatal days (P)2 and P6.

Embryonic origins of the mouse superior olivary complex.

Many areas of the central nervous system are organized into clusters of cell groups, with component cell groups exhibiting diverse but related functions. One such cluster, the superior olivary complex (SOC), is located in the ventral auditory brainstem in mammals. The SOC is an obligatory contact point for most projection neurons of the ventral cochlear nucleus and plays central roles in many aspects of monaural and binaural information processing.

Rax is a selector gene for mediobasal hypothalamic cell types.

The brain plays a central role in controlling energy, glucose, and lipid homeostasis, with specialized neurons within nuclei of the mediobasal hypothalamus, namely the arcuate (ARC) and ventromedial (VMH), tasked with proper signal integration. Exactly how the exquisite cytoarchitecture and underlying circuitry becomes established within these nuclei remains largely unknown, in part because hypothalamic developmental programs are just beginning to be elucidated. Here, we demonstrate that the Retina and anterior neural fold homeobox (Rax) gene plays a key role in establishing ARC and VMH nuclei in mice.

Phosphorylation of phosducin accelerates rod recovery from transducin translocation.

Purpose: In rods saturated by light, the G protein transducin undergoes translocation from the outer segment compartment, which results in the uncoupling of transducin from its innate receptor, rhodopsin. We measured the kinetics of recovery from this adaptive cellular response, while also investigating the role of phosducin, a phosphoprotein binding transducin βγ subunits in its de-phosphorylated state, in regulating this process.

Methods: Mice were exposed to a moderate rod-saturating light triggering transducin translocation, and then allowed to recover in the dark while free running.

Maturation of synaptic partners: functional phenotype and synaptic organization tuned in synchrony.

Maturation of principal neurons of the medial nucleus of the trapezoid body (MNTB) was assessed in the context of the developmental organization and activity of their presynaptic afferents, which grow rapidly to form calyces of Held and to establish mono-innervation between postnatal days (P)2 and 4. MNTB neurons and their inputs were studied from embryonic day (E)17, when the nucleus was first discernable, until P14 after the onset of hearing. Using a novel slice preparation containing portions of the cochlea, cochlear nucleus and MNTB, we determined that synaptic inputs form onto MNTB neurons at E17 and stimulation of the cochlear nucleus can evoke action potentials (APs) and Ca(2+) signals.

Does the brain connect before the periphery can direct? A comparison of three sensory systems in mice.

The development of peripheral to central neural connections within the auditory, visual, and olfactory systems of mice is reviewed to address whether peripheral signaling may play an instructive role during initial synapse formation. For each sensory system, developmental times of histogenesis and the earliest ages of innervation and function are considered for peripheral and selected central relays. For the auditory and visual system, anatomical and functional reports indicate that central connections may form prior to synapse formation in the periphery.

Otitis media with effusion: a possible role for Helicobacter pylori?

Objectives: To compare Helicobacter pylori prevalence rates in the nasopharynx of pediatric patients with and without otitis media with effusion (OME).

Study Design: Prospective, controlled.

Methods: The study group consisted of patients undergoing adenoidectomy for persistent OME.

Molecular guidance cues necessary for axon pathfinding from the ventral cochlear nucleus.

During development, multiple guidance cues direct the formation of appropriate synaptic connections. Factors that guide developing axons are known for various pathways throughout the mammalian brain; however, signals necessary to establish auditory connections are largely unknown. In the auditory brainstem the neurons whose axons traverse the midline in the ventral acoustic stria (VAS) are primarily located in the ventral cochlear nucleus (VCN) and project bilaterally to the superior olivary complex (SOC).

Distinct subtypes of somatostatin-containing neocortical interneurons revealed in transgenic mice.

GABA-releasing inhibitory interneurons in the cerebral cortex can be classified by their neurochemical content, firing patterns, or axonal targets, to name the most common criteria, but whether classifications using different criteria converge on the same neuronal subtypes, and how many such subtypes exist, is a matter of much current interest and considerable debate. To address these issues, we generated transgenic mice expressing green fluorescent protein (GFP) under control of the GAD67 promoter. In two of these lines, named X94 and X98, GFP expression in the barrel cortex was restricted to subsets of somatostatin-containing (SOM+) GABAergic interneurons, similar to the previously reported "GIN" line (Oliva et al.

Detection of fungi in the sinus mucosa using polymerase chain reaction.

Objective: To compare the presence of fungi in the sinus mucosa of patients with and without chronic rhinosinusitis.

Study Design And Setting: Prospective observational study using polymerase chain reaction and conventional culture to detect fungi in the sinus mucosa. Middle meatus mucosal samples were collected from 31 patients with chronic rhinosinusitis and 14 control subjects.

Conditional alleles for activation and inactivation of the mouse Rx homeobox gene.

The Rx homeobox gene is a transcriptional regulator indispensable for development of the eye and ventral forebrain. Rx-null homozygotes lack optic pits, which are the earliest ocular structures. To study the roles Rx may play at various stages of eye and brain development, we generated an allelic series at the Rx locus.

Regulation of vertebrate eye development by Rx genes.

The paired-like homeobox-containing gene Rx has a critical role in the eye development of several vertebrate species including Xenopus, mouse, chicken, medaka, zebrafish and human. Rx is initially expressed in the anterior neural region of developing embryos, and later in the retina and ventral hypothalamus. Abnormal regulation or function of Rx results in severe abnormalities of eye formation.

Mutations in the human RAX homeobox gene in a patient with anophthalmia and sclerocornea.

Anophthalmia and microphthalmia are among the most common ocular birth defects and a significant cause of congenital blindness. The etiology of anophthalmia and microphthalmia is diverse, with multiple genetic mutations associated with each of these conditions, along with potential environmental causes. Based on findings that mutations in the Rx/Rax homeobox genes in mice and fish lead to defects in retinal development and result in animal models of anophthalmia, we screened 75 individuals with anophthalmia and/or microphthalmia for mutations in the human RAX gene.

Brain-derived neurotrophic factor mediates activity-dependent dendritic growth in nonpyramidal neocortical interneurons in developing organotypic cultures.

Brain-derived neurotrophic factor (BDNF) promotes postnatal maturation of GABAergic inhibition in the cerebral and cerebellar cortices, and its expression and release are enhanced by neuronal activity, suggesting that it acts in a feedback manner to maintain a balance between excitation and inhibition during development. BDNF promotes differentiation of cerebellar, hippocampal, and neostriatal inhibitory neurons, but its effects on the dendritic development of neocortical inhibitory interneurons remain unknown. Here, we show that BDNF mediates depolarization-induced dendritic growth and branching in neocortical interneurons.

Role of anaerobes in chronic sinusitis: Will polymerase chain reaction solve the debate.

Background: Bacteriology of chronic sinusitis continues to be a matter of debate, particularly the role of anaerobes. Some authors suggest that anaerobes play a significant role whereas others suggest a minimal role. Those who suggest a significant role argue that standard culture techniques are the culprits.