Spectrin-beta 2 facilitates the selective accumulation of GABA receptors at somatodendritic synapses.

Fast synaptic inhibition is dependent on targeting specific GABAR subtypes to dendritic and axon initial segment (AIS) synapses. Synaptic GABARs are typically assembled from α1-3, β and γ subunits. Here, we isolate distinct GABARs from the brain and interrogate their composition using quantitative proteomics.

Analyzing the mechanisms that facilitate the subtype-specific assembly of -aminobutyric acid type A receptors.

Impaired inhibitory signaling underlies the pathophysiology of many neuropsychiatric and neurodevelopmental disorders including autism spectrum disorders and epilepsy. Neuronal inhibition is regulated by synaptic and extrasynaptic -aminobutyric acid type A receptors (GABA Rs), which mediate phasic and tonic inhibition, respectively. These two GABA R subtypes differ in their function, ligand sensitivity, and physiological properties.

Behavioral and Molecular Consequences of Chronic Sleep Restriction During Development in Fragile X Mice.

Sleep is critical for brain development and synaptic plasticity. In male wild-type mice, chronic sleep restriction during development results in long-lasting impairments in behavior including hypoactivity, decreased sociability, and increased repetitive behavior. Disordered sleep is characteristic of many neurodevelopmental disorders.

Effects of Treatment With Hypnotics on Reduced Sleep Duration and Behavior Abnormalities in a Mouse Model of Fragile X Syndrome.

Many patients with fragile X syndrome (FXS) have sleep disturbances, and knockout (KO) mice (a model of FXS) have reduced sleep duration compared to wild type (WT). Sleep is important for brain development, and chronic sleep restriction during development has long-lasting behavioral effects in WT mice. We hypothesized that the sleep abnormalities in FXS may contribute to behavioral impairments and that increasing sleep duration might improve behavior.

Behavior Testing in Rodents: Highlighting Potential Confounds Affecting Variability and Reproducibility.

Rodent models of brain disorders including neurodevelopmental, neuropsychiatric, and neurodegenerative diseases are essential for increasing our understanding of underlying pathology and for preclinical testing of potential treatments. Some of the most important outcome measures in such studies are behavioral. Unfortunately, reports from different labs are often conflicting, and preclinical studies in rodent models are not often corroborated in human trials.

Sleep Duration in Mouse Models of Neurodevelopmental Disorders.

Sleep abnormalities are common in patients with neurodevelopmental disorders, and it is thought that deficits in sleep may contribute to the unfolding of symptoms in these disorders. Appreciating sleep abnormalities in neurodevelopmental disorders could be important for designing a treatment for these disorders. We studied sleep duration in three mouse models by means of home-cage monitoring: (tuberous sclerosis complex), oxytocin receptor () knockout (KO) (autism spectrum disorders), and KO (Phelan-McDermid syndrome).

Characterization of the development of the mouse cochlear epithelium at the single cell level.

Mammalian hearing requires the development of the organ of Corti, a sensory epithelium comprising unique cell types. The limited number of each of these cell types, combined with their close proximity, has prevented characterization of individual cell types and/or their developmental progression. To examine cochlear development more closely, we transcriptionally profile approximately 30,000 isolated mouse cochlear cells collected at four developmental time points.

Sex-Selective Effects on Behavior in a Mouse Model of Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder that is caused by a mutation in either or TSC affects multiple systems of the body, and patients with TSC display a range of neurologic and behavioral manifestations including seizures, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder, anxiety, and mood disorders. Whereas behavioral phenotypes of many mouse models have been studied, the effects of sex have, for the most part, not been explored. We studied adult male and female heterozygous and control mice to investigate the influence of sex and genotype on behavior.

GSK3 regulates hair cell fate in the developing mammalian cochlea.

The development of asymmetric patterns along biologically relevant axes is a hallmark of many vertebrate organs or structures. One example is the sensory epithelium of the mammalian auditory system. Two distinct types of mechanosensory hair cells (inner and outer) and at least six types of associated supporting cells are precisely and asymmetrically arrayed along the radial (medial-lateral) axis of the cochlear spiral.

Chronic Sleep Restriction in Developing Male Mice Results in Long Lasting Behavior Impairments.

Sleep abnormalities are prevalent in autism spectrum disorders (ASD). Moreover, the severity of ASD symptoms are correlated with the degree of disturbed sleep. We asked if disturbed sleep during brain development itself could lead to ASD-like symptoms, particularly behavioral manifestations.

Comparative Behavioral Phenotypes of KO, Het, and KO/ Het Mice.

Fragile X syndrome (FXS) is caused by silencing of the gene leading to loss of the protein product fragile X mental retardation protein (FMRP). FXS is the most common monogenic cause of intellectual disability. There are two known mammalian paralogs of FMRP, FXR1P, and FXR2P.

Chronic Sleep Deprivation in Mouse Pups by Means of Gentle Handling.

Sleep is critical for proper development and neural plasticity. Moreover, abnormal sleep patterns are characteristic of many neurodevelopmental disorders. Studying how chronic sleep restriction during development can affect adult behavior may add to our understanding of the emergence of behavioral symptoms of neurodevelopmental disorders.

Noninvasive, High-throughput Determination of Sleep Duration in Rodents.

Traditionally, sleep is monitored by an electroencephalogram (EEG). EEG studies in rodents require surgical implantation of the electrodes followed by a long recovery period. To perform an EEG recording, the animal is connected to a receiver, creating an unnatural tether to the head-mount.

Negative Effects of Chronic Rapamycin Treatment on Behavior in a Mouse Model of Fragile X Syndrome.

Fragile X syndrome (FXS), the most common form of inherited intellectual disability, is also highly associated with autism spectrum disorders (ASD). It is caused by expansion of a CGG repeat sequence on the X chromosome resulting in silencing of the gene. This is modeled in the mouse by deletion of ( KO).