Sex differences in sleep deficits in mice with an autism-linked Shank3 mutation.

Background: Insomnia is more prevalent in individuals with Autism Spectrum Disorder (ASD), can worsen core-symptoms and reduces quality of life of both individuals and caregivers. Although ASD is four times more prevalent in males than females, less is known about sex specific sleep differences in autistic individuals. Recent ASD studies suggest that sleep problems may be more severe in females, which aligns with the sex bias seen in insomnia for the general population.

A global transcriptional atlas of the effect of acute sleep deprivation in the mouse frontal cortex.

Sleep deprivation (SD) has negative effects on brain and body function. Sleep problems are prevalent in a variety of disorders, including neurodevelopmental and psychiatric conditions. Thus, understanding the molecular consequences of SD is of fundamental importance in biology.

A Global Transcriptional Atlas of the Effect of Sleep Deprivation in the Mouse Frontal Cortex.

Sleep deprivation (SD) has negative effects on brain function. Sleep problems are prevalent in neurodevelopmental, neurodegenerative and psychiatric disorders. Thus, understanding the molecular consequences of SD is of fundamental importance in neuroscience.

Shank3 influences mammalian sleep development.

Sleep problems are prevalent in autism spectrum disorder (ASD), can be observed before diagnosis, and are associated with increased restricted and repetitive behaviors. Therefore, sleep abnormalities may be a core feature of the disorder, but the developmental trajectory remains unknown. Animal models provide a unique opportunity to understand sleep ontogenesis in ASD.

Age- and sex-specific fear conditioning deficits in mice lacking Pcdh10, an Autism Associated Gene.

PCDH10 is a gene associated with Autism Spectrum Disorder. It is involved in the growth of thalamocortical projections and dendritic spine elimination. Previously, we characterized Pcdh10 haploinsufficient mice (Pcdh10 mice) and found male-specific social deficits and dark phase hypoactivity.

Comprehensive Behavioral Phenotyping of a 16p11.2 Del Mouse Model for Neurodevelopmental Disorders.

The microdeletion of copy number variant 16p11.2 is one of the most common genetic mutations associated with neurodevelopmental disorders, such as Autism Spectrum Disorders (ASDs). Here, we describe our comprehensive behavioral phenotyping of the 16p11.

Sleep, brain development, and autism spectrum disorders: Insights from animal models.

Sleep is an evolutionarily conserved and powerful drive, although its complete functions are still unknown. One possible function of sleep is that it promotes brain development. The amount of sleep is greatest during ages when the brain is rapidly developing, and sleep has been shown to influence critical period plasticity.

Transcriptional corepressor SIN3A regulates hippocampal synaptic plasticity via Homer1/mGluR5 signaling.

Long-term memory depends on the control of activity-dependent neuronal gene expression, which is regulated by epigenetic modifications. The epigenetic modification of histones is orchestrated by the opposing activities of 2 classes of regulatory complexes: permissive coactivators and silencing corepressors. Much work has focused on coactivator complexes, but little is known about the corepressor complexes that suppress the expression of plasticity-related genes.

Ventral pallidum is essential for cocaine relapse after voluntary abstinence in rats.

Addiction is a chronic relapsing disorder, and during recovery many people experience several relapse events as they attempt to voluntarily abstain from drug. New preclinical relapse models have emerged that capture this common human experience, and mounting evidence indicates that resumption of drug seeking after voluntary abstinence recruits neural circuits distinct from those recruited during reinstatement after experimenter-imposed abstinence, or abstinence due to extinction training. Ventral pallidum (VP), a key limbic node involved in drug seeking, has well-established roles in conventional reinstatement models tested following extinction training, but it is unclear whether this region also participates in more translationally relevant models of relapse.

Shank3 modulates sleep and expression of circadian transcription factors.

Autism Spectrum Disorder (ASD) is the most prevalent neurodevelopmental disorder in the United States and often co-presents with sleep problems. Sleep problems in ASD predict the severity of ASD core diagnostic symptoms and have a considerable impact on the quality of life of caregivers. Little is known, however, about the underlying molecular mechanisms of sleep problems in ASD.

Linking spatial gene expression patterns to sex-specific brain structural changes on a mouse model of 16p11.2 hemideletion.

Neurodevelopmental disorders, such as ASD and ADHD, affect males about three to four times more often than females. 16p11.2 hemideletion is a copy number variation that is highly associated with neurodevelopmental disorders.

Modeling cocaine relapse in rodents: Behavioral considerations and circuit mechanisms.

Addiction is a chronic relapsing disorder, in that most addicted individuals who choose to quit taking drugs fail to maintain abstinence in the long-term. Relapse is especially likely when recovering addicts encounter risk factors like small "priming" doses of drug, stress, or drug-associated cues and locations. In rodents, these same factors reinstate cocaine seeking after a period of abstinence, and extensive preclinical work has used priming, stress, or cue reinstatement models to uncover brain circuits underlying cocaine reinstatement.

Sociability Deficits and Altered Amygdala Circuits in Mice Lacking Pcdh10, an Autism Associated Gene.

Background: Behavioral symptoms in individuals with autism spectrum disorder (ASD) have been attributed to abnormal neuronal connectivity, but the molecular bases of these behavioral and brain phenotypes are largely unknown. Human genetic studies have implicated PCDH10, a member of the δ2 subfamily of nonclustered protocadherin genes, in ASD. PCDH10 expression is enriched in the basolateral amygdala, a brain region implicated in the social deficits of ASD.

Object-location training elicits an overlapping but temporally distinct transcriptional profile from contextual fear conditioning.

Hippocampus-dependent learning is known to induce changes in gene expression, but information on gene expression differences between different learning paradigms that require the hippocampus is limited. The bulk of studies investigating RNA expression after learning use the contextual fear conditioning task, which couples a novel environment with a footshock. Although contextual fear conditioning has been useful in discovering gene targets, gene expression after spatial memory tasks has received less attention.

Transcriptional co-repressors and memory storage.

Epigenetic modifications are a central mechanism for regulating chromatin structure and gene expression in the brain. A wide array of histone- and DNA-modifying enzymes have been identified as critical regulators of neuronal function, memory formation, and as causative agents in neurodevelopmental and neuropsychiatric disorders. Chromatin modifying enzymes are frequently incorporated into large multi-protein co-activator and co-repressor complexes, where the activity of multiple enzymes is both spatially and temporally coordinated.

Distinct retinal pathways drive spatial orientation behaviors in zebrafish navigation.

Navigation requires animals to adjust ongoing movements in response to pertinent features of the environment and select between competing target cues. The neurobiological basis of navigational behavior in vertebrates is hard to analyze, partly because underlying neural circuits are experience dependent. Phototaxis in zebrafish is a hardwired navigational behavior, performed at a stage when larvae swim by using a small repertoire of stereotyped movements.