Damon Page

Damon Page
The Scripps Research Institute | scripps · Department of Neuroscience

About

42
Publications
6,200
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
1,814
Citations
Citations since 2016
18 Research Items
1355 Citations
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250
Additional affiliations
July 2011 - present
The Scripps Research Institute
Position
  • Professor (Associate)

Publications

Publications (42)
Chapter
Humans spend the majority of our time interacting with others, and thus social skills are essential. Therefore, advances in our understanding of the neurobiological underpinnings of social behavior are of critical importance. Social behavior is a broad, complex category involving many different neural circuits, skills, and motivations. In this chap...
Article
Full-text available
How changes in brain scaling relate to altered behavior is an important question in neurodevelopmental disorder research. Mice with germline Pten haploinsufficiency (Pten+/-) closely mirror the abnormal brain scaling and behavioral deficits seen in humans with macrocephaly/autism syndrome, which is caused by PTEN mutations. We explored whether devi...
Article
Full-text available
Molecular and cellular mechanisms underlying the role of the prelimbic cortex in contextual fear memory remain elusive. Here we examined the kinesin family of molecular motor proteins (KIFs) in the prelimbic cortex for their role in mediating contextual fear, a form of associative memory. KIFs function as critical mediators of synaptic transmission...
Article
Full-text available
Pten germline haploinsufficient (Pten+/−) mice, which model macrocephaly/autism syndrome, show social and repetitive behavior deficits, early brain overgrowth, and cortical–subcortical hyperconnectivity. Previous work indicated that altered neuronal connectivity may be a substrate for behavioral deficits. We hypothesized that exposing Pten+/− mice...
Article
Full-text available
Synaptic structural plasticity, key to long-term memory storage, requires translation of localized RNAs delivered by long-distance transport from the neuronal cell body. Mechanisms and regulation of this system remain elusive. Here, we explore the roles of KIF5C and KIF3A, two members of kinesin superfamily of molecular motors (Kifs), and find that...
Article
Full-text available
Background Mutations in DYRK1A are a cause of microcephaly, autism spectrum disorder, and intellectual disability; however, the underlying cellular and molecular mechanisms are not well understood. Methods We generated a conditional mouse model using Emx1-cre, including conditional heterozygous and homozygous knockouts, to investigate the necessit...
Preprint
Full-text available
Impaired synaptic function is a common phenotype in animal models for autism spectrum disorder (ASD), and ASD risk genes are enriched for synaptic function. Here we leverage the availability of multiple ASD mouse models exhibiting synaptic deficits and behavioral correlates of ASD and use quantitative mass spectrometry with isobaric tandem mass tag...
Article
Full-text available
The prefrontal cortex and amygdala are anatomical substrates linked to both social information and emotional valence processing, but it is not known whether sub-circuits in the medial prefrontal cortex (mPFC) that project to the basolateral amygdala (BLA) are recruited and functionally contribute to social approach-avoidance behavior. Using retrogr...
Article
Full-text available
Mutations that inactivate negative translation regulators cause autism spectrum disorders (ASD), which predominantly affect males and exhibit social interaction and communication deficits and repetitive behaviors. However, the cells that cause ASD through elevated protein synthesis resulting from these mutations remain unknown. Here we employ condi...
Article
A subset of individuals with autism spectrum disorder (ASD) and macrocephaly carry mutations in the gene PTEN. Animal models, particularly mice, have been helpful in establishing a causal role for Pten mutations in autism-relevant behavioral deficits. These models are a useful tool for investigating neurobiological mechanisms of these behavioral ph...
Article
Full-text available
Haploinsufficiency for PTEN is a cause of autism spectrum disorder and brain overgrowth; however, it is not known if PTEN mutations disrupt scaling across brain areas during development. To address this question, we used magnetic resonance imaging to analyze brains of male Pten haploinsufficient (Pten+/−) mice and wild-type littermates during early...
Article
Heterozygous mutations in PTEN, which encodes a negative regulator of the mTOR and β‐catenin signaling pathways, cause macrocephaly/autism syndrome. However, the neurobiological substrates of the core symptoms of this syndrome are poorly understood. Here, we investigate the relationship between cerebral cortical overgrowth and social behavior defic...
Article
Full-text available
There is a pressing need to improve approaches for drug discovery related to neuropsychiatric disorders (NSDs). Therapeutic discovery in neuropsychiatric disorders would benefit from screening assays that can measure changes in complex phenotypes linked to disease mechanisms. However, traditional assays that track complex neuronal phenotypes, such...
Article
Full-text available
Multiple autism risk genes converge on the regulation of mTOR signalling, which is a key effector of neuronal growth and connectivity. We show that mTOR signalling is dysregulated during early postnatal development in the cerebral cortex of germ-line heterozygous Pten mutant mice (Pten þ / À), which model macrocephaly/autism syndrome. The basolater...
Article
The precise molecular and cellular events responsible for age-dependent cognitive dysfunctions remain unclear. We report that small guanine nucleotide-binding protein Rheb (ras homolog enriched in brain), an activator of mammalian target of rapamycin (mTOR), regulates memory functions in mice. Conditional depletion of Rheb selectively in the forebr...
Article
Full-text available
Zika virus (ZIKV) infection in pregnant women has been established as a cause of microcephaly in newborns. Here we test the hypothesis that neurodevelopmental stages when the brain is undergoing rapid growth are particularly vulnerable to the effects of ZIKV infection. We injected ZIKV intracranially into wild type C57BL/6 mice at two different tim...
Article
Germline heterozygous mutations in Pten (phosphatase and tensin homolog) are associated with macrocephaly and autism spectrum disorders (ASD). Pten germline heterozygous (Pten(+/-) ) mice approximate these mutations, and both sexes show widespread brain overgrowth and impaired social behavior. Strikingly similar behavior phenotypes have been report...
Article
Full-text available
The development of social behavior is strongly influenced by the serotonin system. Serotonin 2c receptor (5-HT2cR) is particularly interesting in this context considering that pharmacological modulation of 5-HT2cR activity alters social interaction in adult rodents. However, the role of 5-HT2cR in the development of social behavior is unexplored. H...
Article
Full-text available
Abnormal patterns of head and brain growth are a replicated finding in a subset of individuals with autism spectrum disorder (ASD). It is not known whether risk factors associated with ASD and abnormal brain growth (both overgrowth and undergrowth) converge on common biological pathways and cellular mechanisms in the developing brain. Heterozygous...
Article
Huntington disease (HD) is caused by an expansion of glutamine repeats in the huntingtin protein (mHtt) that invokes early and prominent damage of the striatum, a region that controls motor behaviors. Despite its ubiquitously expression, why certain brain regions, such as the cerebellum, are relatively spared from neuronal loss by mHtt remains uncl...
Article
Aggression is an aspect of social behavior that can be elevated in some individuals with autism spectrum disorder (ASD), and a concern for peers and caregivers. Mutations in Phosphatase and tensin homolog (PTEN), one of several ASD risk factors encoding negative regulators of the PI3K-Akt-mTOR pathway, have been reported in individuals with ASD and...
Article
Full-text available
In patients with Huntington's disease (HD), the protein huntingtin (Htt) has an expanded polyglutamine (poly-Q) tract. HD results in early loss of medium spiny neurons in the striatum, which impairs motor and cognitive functions. Identifying the physiological role and molecular functions of Htt may yield insight into HD pathogenesis. We found that...
Article
Background Genetic haploinsufficiency of Syngap1 commonly occurs in developmental brain disorders, such as intellectual disability (ID), epilepsy, schizophrenia (SCZ), and autism spectrum (ASD) disorder. Thus, studying mouse models of Syngap1 haploinsufficiency may uncover pathological developmental processes common among distinct brain disorders....
Article
To provide a temporal framework for the genoarchitecture of brain development, we generated in situ hybridization data for embryonic and postnatal mouse brain at seven developmental stages for ∼2,100 genes, which were processed with an automated informatics pipeline and manually annotated. This resource comprises 434,946 images, seven reference atl...
Article
Full-text available
Accelerated head and brain growth (macrocephaly) during development is a replicated biological finding in a subset of individuals with autism spectrum disorder (ASD). However, the relationship between brain overgrowth and the behavioral and cognitive symptoms of ASD is poorly understood. The PI3K–Akt–mTOR pathway regulates cellular growth; several...
Article
Although there have been major advances in elucidating the functional biology of the human brain, relatively little is known of its cellular and molecular organization. Here we report a large-scale characterization of the expression of ∼1,000 genes important for neural functions by in situ hybridization at a cellular resolution in visual and tempor...
Article
A major problem in understanding mechanisms of pathogenesis in autism spectrum disorder (ASD) is deciphering how risk factors act via the brain to influence the behavioral symptoms of this disorder. We may start to bridge this gap in our understanding by systematically examining the structure and function of cell types that make up circuits underly...
Article
Full-text available
Assays of social approach behavior involve measuring the social investigatory behavior of a subject mouse toward a stimulus mouse. Such assays represent a phenotyping tool that may be applied to mouse models of mood and anxiety disorders, as well as other neuropsychiatric disease, to understand how genetic and environmental risk factors impact brai...
Article
The mammalian brain is best understood as a multi-scale hierarchical neural system, in the sense that connection and function occur on multiple scales from micro to macro. Modern genomic-scale expression profiling can provide insight into methodologies that elucidate this architecture. We present a methodology for understanding the relationship of...
Article
Full-text available
Altered sociability is a core feature of a variety of human neurological disorders, including autism. Social behaviors may be tested in animal models, such as mice, to study the biological basis of sociability and how this is altered in neurodevelopmental disorders. A quantifiable social behavior frequently used to assess sociability in the mouse i...
Article
Full-text available
Primary sensory nuclei of the thalamus process and relay parallel channels of sensory input into the cortex. The developmental processes by which these nuclei acquire distinct functional roles are not well understood. To identify novel groups of genes with a potential role in differentiating two adjacent sensory nuclei, we performed a microarray sc...
Article
The inhibitory GABAergic system has been implicated in multiple neuropsychiatric diseases such as schizophrenia and autism. The Dlx homeobox transcription factor family is essential for development and function of GABAergic interneurons. Mice lacking the Dlx1 gene have postnatal subtype-specific loss of interneurons and reduced IPSCs in their corte...
Article
Full-text available
Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders that share deficits in sociability, communication, and restrictive and repetitive interests. ASD is likely polygenic in origin in most cases, but we presently lack an understanding of the relationships between ASD susceptibility genes and the neurobiological and...
Article
At the end of embryogenesis, the ventral nerve cord (VNC) of Drosophila undergoes a shape change, termed condensation. During condensation the length of the VNC shortens by 25%, a process dependent on extracellular matrix deposited by hemocytes, an intact cytoskeleton of glia and neurons and neural activity. Here we show that cell death contributes...
Article
Condensation is a process whereby a tissue undergoes a coordinated decrease in size and increase in cellular density during development. Although it occurs in many developmental contexts, the mechanisms underlying this process are largely unknown. Here, we investigate condensation in the embryonic Drosophila ventral nerve cord (VNC). Two major even...
Article
The evolutionary origin of the tritocerebral neuromere, which is a brain segment located at the junction between the supra- and subesophageal ganglia in most mandibulates (arthropods such as crustaceans and insects), is a subject rich in contentious debate. Various models have argued that the tritocerebrum came from a segmental nerve cord ganglia t...
Article
In invertebrates and vertebrates, neural midline cells secrete signals that pattern the central nervous system (CNS). However, an important part of the developing insect brain, involved in functions such as olfaction and feeding behavior, is positioned lateral to the foregut and lacks neural cells at the midline. Could the foregut substitute for ne...
Article
Full-text available
In vertebrates (deuterostomes), brain patterning depends on signals from adjacent tissues. For example, holoprosencephaly, the most common brain anomaly in humans, results from defects in signaling between the embryonic prechordal plate (consisting of the dorsal foregut endoderm and mesoderm) and the brain. I have examined whether a similar mechani...
Article
Full-text available
Drosophila embryos lacking the homeotic gene labial (lab) show two types of defects in brain development: (1) cells in the brain lab domain do not express neuronal markers or extend axons, and (2) axons originating from outside the lab domain stop at this region or project ectopically. A severe disruption of neuronal patterning and axon scaffolding...
Article
Full-text available
Drosophila embryos lacking the homeotic gene labial (lab) show two types of defects in brain development: (1) cells in the brain lab domain do not express neuronal markers or extend axons, and (2) axons originating from outside the lab domain stop at this region or project ectopically. A severe disruption of neuronal patterning and axon scaffolding...

Network

Cited By