A5000274961- Neuroendocrine regulation and behavior
- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Infant Health and Development
- Child Development and Digital Technology
- Congenital heart defects research
- Neuroscience of respiration and sleep
- Genomic variations and chromosomal abnormalities
- RNA modifications and cancer
- Memory and Neural Mechanisms
- Stress Responses and Cortisol
- Human-Animal Interaction Studies
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- Animal Vocal Communication and Behavior
- Photoreceptor and optogenetics research
- Neuroscience and Neuropharmacology Research
- Neural and Behavioral Psychology Studies
- Animal Genetics and Reproduction
- Child and Animal Learning Development
- Cognitive Science and Mapping
- Sleep and Wakefulness Research
- RNA regulation and disease
- Attention Deficit Hyperactivity Disorder
- Microtubule and mitosis dynamics
Icahn School of Medicine at Mount Sinai
2015-2025
Child Health and Development Institute
2015-2025
Allen Institute for Brain Science
2015-2025
New York Proton Center
2025
Center for Autism and Related Disorders
2016-2025
Heidelberg University
2022
Central Institute of Mental Health
2022
University Hospital Heidelberg
2022
Neurosciences Institute
2022
University of Haifa
2013-2020
Mutations in the synaptic gene SHANK3 lead to a neurodevelopmental disorder known as Phelan-McDermid syndrome (PMS). PMS is relatively common monogenic and highly penetrant cause of autism spectrum (ASD) intellectual disability (ID), frequently presents with attention deficits. The underlying neurobiology not fully pharmacological treatments for core symptoms do exist. Here, we report production characterization Shank3-deficient rat model PMS, genetic alteration similar human mutation. We...
Mutations in the SHANK3 gene have been discovered autism spectrum disorder (ASD), and intellectual disability, Phelan‐McDermid Syndrome. This study leveraged a new rat model of Shank3 deficiency to assess complex behavioral phenomena, unique rats, which display richer social behavior repertoire than mice. Uniquely detectable emissions ultrasonic vocalizations (USV) rats serve as situation‐dependent affective signals accomplish important communicative functions. We report, for first time,...
Copy number variations encompassing the gene encoding Cyfip1 have been associated with a variety of human diseases, including autism and schizophrenia. Here we show that juvenile mice hemizygous for altered presynaptic function, enhanced protein translation, increased levels F-actin. In developing hippocampus, reduced serve to decrease paired pulse facilitation increase miniature EPSC frequency without change in amplitude. Higher-resolution examination shows these changes be caused primarily...
Abstract Oxytocin plays an important role in modulating social recognition memory. However, the direct implication of oxytocin neurons paraventricular nucleus hypothalamus (PVH) and their downstream hypothalamic targets regulating short- long-term forms memory has not been fully investigated. In this study, we employed a chemogenetic approach to target activity PVH male rats found that specific silencing neuronal population led impairment We combined viral-mediated fluorescent labeling with...
BackgroundThe posterior intralaminar (PIL) complex of the thalamus is a multimodal nucleus that has been implicated in maternal behaviors and conspecific social male female rodents. Glutamatergic neurons are major component PIL; however, their specific activity role during interactions not yet assessed.MethodsWe used immunohistochemistry for immediate early gene c-fos as proxy neuronal PIL mice exposed to novel stimulus, object or no stimulus. We then fiber photometry record neural...
Abstract Social behaviors are crucial for human connection and belonging, often impacted by conditions like Autism Spectrum Disorder (ASD). The mesoaccumbens pathway (ventral tegmental area (VTA) to the nucleus accumbense (NAc)) plays a pivotal role in social behavior is implicated ASD. However, impact of ASD‐related mutations on reward processing remains insufficiently explored. This study focuses Shank3 mutation, associated with rare genetic condition linked ASD, examining its influence...
Adolescent social interactions are essential for shaping adult behavior in humans. While rodent studies have highlighted the impact of isolation on behavior, many extend into adulthood, making it challenging to pinpoint long-term consequences juvenile isolation. To address these challenges, we examined effects using two independent protocols with male and female Sprague Dawley rats. In both prfotocols, rats were isolated during stage; however, one protocol, re-socialized following tested...
The genetics of autism spectrum disorder (hereafter referred to as "autism") are rapidly unfolding, with a significant increase in the identification genes implicated disorder. Many these part complex landscape genetic variants that thought act together cause behavioral phenotype associated autism. One few single-locus causes involves mutation SH3 and multiple ankyrin repeat domains 3 (SHANK3) gene. Previous electrophysiological studies mice Shank3 mutations demonstrated impairment synaptic...
Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by mutations in the FMR1 gene. It leading monogenic cause of autism spectrum and inherited intellectual disability often comorbid with attention deficits. Most FXS cases are due to an expansion CGG repeats suppressed expression fragile mental retardation protein (FMRP), RNA-binding involved mRNA metabolism. We found that previously published Fmr1 knockout rat model expresses transcript in-frame deletion exon 8, which encodes...
Abstract Background Deletion or mutations of SHANK3 lead to Phelan–McDermid syndrome and monogenic forms autism spectrum disorder (ASD). encodes its eponymous scaffolding protein at excitatory glutamatergic synapses. Altered morphology dendrites spines in the hippocampus, cerebellum, striatum have been associated with behavioral impairments Shank3-deficient animal models. Given attentional deficit these animals, our study explored whether deficiency Shank3 a rat model alters neuron synaptic...
Individuals with SHANK3 mutations have severely impaired receptive and expressive language abilities. While brain responses are known to be abnormal in these individuals, the auditory cortex response sound has remained largely understudied. In this study, we document speech non‐speech sounds novel Shank3‐ deficient rat model. We predicted that would rats. found were weaker Shank3 heterozygous rats compared wild‐type Additionally, had less spontaneous firing unable respond well rapid trains...
Abstract Background Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene and characterized global developmental delays, deficits in speech motor function, autism spectrum (ASD). Monogenic causes ASD such as PMS are well suited to investigations with novel therapeutics, interventions can be targeted based on established genetic etiology. While preclinical studies have demonstrated that neuropeptide oxytocin reverse...
Abstract Hypothalamic oxytocin (OXT) and arginine-vasopressin (AVP) neurons have been at the center of several physiological behavioral studies. Advances in viral vector biology development transgenic rodent models allowed for targeted gene expression to study functions specific cell populations brain circuits. In this study, we compared efficiency various adeno-associated vectors these demonstrated that none widely used promoters were, on their own, effective driving a down-stream...
Abstract Mutations and deletions in the SHANK3 gene cause major neurodevelopmental features of Phelan–McDermid syndrome (PMS), which is characterized by intellectual disability, autism spectrum disorder, sensory hyporeactivity. encodes a key structural component excitatory synapses important for synaptogenesis. Clinical assessments limited brain imaging studies patients with PMS have uncovered regional volume reductions white matter thinning. While these impairments been replicated ex vivo...
ABSTRACT Background The posterior intralaminar (PIL) complex of the thalamus is a multimodal nucleus that has been implicated in maternal behaviors and conspecific social male female rodents. Glutamatergic neurons are major component PIL; however, their specific activity role during interactions not yet assessed. Methods We used immunohistochemistry for immediate early gene c-fos as proxy neuronal PIL mice exposed to novel stimulus, object or no stimulus. then fiber photometry record neural...