A chromosome region linked to neurodevelopmental disorders acts in distinct neuronal circuits in males and females to control locomotor behavior.

Unlabelled: Biological sex shapes the manifestation and progression of neurodevelopmental disorders (NDDs). These disorders often demonstrate male-specific vulnerabilities; however, the identification of underlying mechanisms remains a significant challenge in the field. Hemideletion of the 16p11.

Excess neonatal testosterone causes male-specific social and fear memory deficits in wild-type mice.

Neurodevelopmental disorders (ND) disproportionately affect males compared to females, and Autism Spectrum Disorder (ASD) in particular exhibits a 4:1 male bias. The biological mechanisms of this female protection or male susceptibility have not been identified. There is some evidence to suggest that fetal/neonatal gonadal hormones, which play pivotal roles in many aspects of development, may contribute.

The γ-Protocadherins Interact Physically and Functionally with Neuroligin-2 to Negatively Regulate Inhibitory Synapse Density and Are Required for Normal Social Interaction.

Cell adhesion molecules (CAMs) are key players in the formation of neural circuits during development. The γ-protocadherins (γ-Pcdhs), a family of 22 CAMs encoded by the Pcdhg gene cluster, are known to play important roles in dendrite arborization, axon targeting, and synapse development. We showed previously that multiple γ-Pcdhs interact physically with the autism-associated CAM neuroligin-1, and inhibit the latter's ability to promote excitatory synapse maturation.

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.

Nolz1 expression is required in dopaminergic axon guidance and striatal innervation.

Midbrain dopaminergic (DA) axons make long longitudinal projections towards the striatum. Despite the importance of DA striatal innervation, processes involved in establishment of DA axonal connectivity remain largely unknown. Here we demonstrate a striatal-specific requirement of transcriptional regulator Nolz1 in establishing DA circuitry formation.

The Role of Synaptic Cell Adhesion Molecules and Associated Scaffolding Proteins in Social Affiliative Behaviors.

Social affiliative behaviors-engagement in positive (i.e., nonaggressive) social approach and reciprocal social interactions with a conspecific-comprise a construct within the National Institute of Mental Health Research Domain Criteria Social Processes Domain.

Sociability development in mice with cell-specific deletion of the NMDA receptor NR1 subunit gene.

Social affiliative behavior is an important component of everyday life in many species and is likely to be disrupted in disabling ways in various neurodevelopmental and neuropsychiatric disorders. Therefore, determining the mechanisms involved in these processes is crucial. A link between N-methyl-d-aspartate (NMDA) receptor function and social behaviors has been clearly established.

Home-cage hypoactivity in mouse genetic models of autism spectrum disorder.

Genome-wide association and whole exome sequencing studies from Autism Spectrum Disorder (ASD) patient populations have implicated numerous risk factor genes whose mutation or deletion results in significantly increased incidence of ASD. Behavioral studies of monogenic mutant mouse models of ASD-associated genes have been useful for identifying aberrant neural circuitry. However, behavioral results often differ from lab to lab, and studies incorporating both males and females are often not performed despite the significant sex-bias of ASD.

Sex Differences in Autism Spectrum Disorder: a Review.

Purpose Of Review: Neurodevelopmental disorders disproportionately affect males. The mechanisms underlying male vulnerability or female protection are not known and remain understudied. Determining the processes involved is crucial to understanding the etiology and advancing treatment of neurodevelopmental disorders.

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.

Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1.

Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure.

Activation of basolateral amygdala in juvenile C57BL/6J mice during social approach behavior.

There is a strong need to better understand the neurobiology of juvenile sociability (tendency to seek social interaction), a phenotype of central relevance to autism spectrum disorders (ASD). Although numerous genetic mouse models of ASD showing reduced sociability have been reported, and certain brain regions, such as the amygdala, have been implicated in sociability, there has been little emphasis on delineating brain structures and circuits activated during social interactions in the critical juvenile period of the mouse strain that serves as the most common genetic background for these models-the highly sociable C57BL/6J (B6) strain. We measured expression of the immediate early genes Fos and Egr-1 to map activation of brain regions following the Social Approach Test (SAT) in juvenile male B6 mice.

Transiently increasing cAMP levels selectively in hippocampal excitatory neurons during sleep deprivation prevents memory deficits caused by sleep loss.

The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation.

Estradiol regulates markers of synaptic plasticity in the hypothalamic ventromedial nucleus and amygdala of female rats.

Ovarian hormones act in multiple brain regions to modulate specific behaviors and emotional states. For example, ovarian hormones promote female sexual receptivity in the hypothalamic ventromedial nucleus (VMH) and modulate anxiety in the amygdala. Hormone-induced changes within the VMH include structural modifications, such as changes in dendritic spines, dendrite length and the number of synapses.

Dendritic arbor of neurons in the hypothalamic ventromedial nucleus in female prairie voles (Microtus ochrogaster).

Female mating behavior in rats is associated with hormone-induced changes in the dendritic arbor of neurons in the ventromedial nucleus of the hypothalamus (VMH), particularly the ventrolateral portion. Regulation of mating behavior in female prairie voles differs substantially from that in rats; therefore, we examined the dendritic morphology of VMH neurons in this species. Sexually naïve adult female prairie voles were housed with a male to activate the females' reproductive endocrine system.

Oxytocin and dendrite remodeling in the hypothalamus.

For most people, their quality of life depends on their successful interdependence with others, which requires sophisticated social cognition, communication, and emotional bonds. Across the lifespan, new bonds must be forged and maintained, and conspecific menaces must be managed. The dynamic nature of the human social landscape suggests ongoing specific alterations in neural circuitry across several brain systems to subserve social behavior.

fruitless Gene products truncated of their male-like qualities promote neural and behavioral maleness in Drosophila if these proteins are produced in the right places at the right times.

To bring GAL4 production under the control of the sex promoter (P1) contained within Drosophila's fruitless gene, a gal4 cassette was previously inserted downstream of P1. This insert should eliminate male-specific FRU(M) proteins, which normally contain 101 amino acids (aa's) at their N termini. Thus males homozygous for the P1-gal4 insert should be courtless, as was briefly stated to be so in the initial report of this transgenic type.

Functional analysis of fruitless gene expression by transgenic manipulations of Drosophila courtship.

A gal4-containing enhancer-trap called C309 was previously shown to cause subnormal courtship of Drosophila males toward females and courtship among males when driving a conditional disrupter of synaptic transmission (shi(TS)). We extended these manipulations to analyze all features of male-specific behavior, including courtship song, which was almost eliminated by driving shi(TS) at high temperature. In the context of singing defects and homosexual courtship affected by mutations in the fru gene, a tra-regulated component of the sex-determination hierarchy, we found a C309/tra(F) combination also to induce high levels of courtship between pairs of males and "chaining" behavior in groups; however, these doubly transgenic males sang normally.