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Principal Investigator: Trishala Chari
Organization: UNIVERSITY OF CALIFORNIA LOS ANGELES
Fiscal Year: 2024
Award: $25,859
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
PROJECT ABSTRACT
Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by deficits in social
interaction, repetitive behaviors and atypical sensory processing. The change in quality of life in ASD individuals
is primarily attributed to social deficits, which can be associated with (or even triggered by) atypical processing
of sensory information. In particular, social touch deficits in ASD may explain this association given the strong
relationship between social interaction deficits and tactile hypersensitivity in ASD. Early tactile hyperresponsivity
predicts future social impairments in ASD children and the absence of touch prevents ASD children from forming
social relationships as adults. ASD individuals also lack representations of affective social touch in
somatosensory brain regions. In mouse models of ASD, tactile sensitivity and social touch interactions also
appear to be linked. Still, several important questions about social touch remain unresolved. First, it is not known
when social touch behavioral deficits first emerge in ASD. These deficits may emerge early on in development
when sensory hypersensitivity first develops or later in adolescence when social experiences become more
frequent. Second, little is known about how social touch and maladaptive behaviors to social touch are
represented in the brain of ASD individuals. Relevant brain areas may include the primary somatosensory cortex
(S1), which encodes social touch and shows impaired adaptation to innocuous tactile stimuli in ASD mouse
models, and the basolateral amygdala (BLA), which is important for encoding aversive stimuli and salient social
information. To investigate social touch deficits in mouse models of autism, I have designed a novel head-fixed
behavioral assay during which behavioral responses to social touch can be measured. This assay allows me to
spatially and temporally control social touch interactions between mice so that I can assess the behavioral
responses to both voluntary (whisker-whisker contact) and forced (snout-snout contact) social touch in a test
mouse as it interacts with a stranger mouse. My preliminary data already shows that both the Fragile X Syndrome
and maternal immune activation mouse models of autism animals display increased avoidance behaviors and
aversive facial expressions (AFEs) to both voluntary and forced social touch compared to their controls in
adulthood. Furthermore, these maladaptive behaviors are more prominent during social touch than object touch.
For this proposal, I will utilize this novel behavioral assay and in vivo silicon probe electrophysiology recordings
(Neuropixels) to 1. investigate when avoidance behaviors and AFEs to social touch emerge during development
(postnatal and juvenile ages) in ASD mice and 2. determine how social touch and the maladaptive behavioral
responses it triggers in ASD are represented as neural dynamics in S1 and BLA. This proposal is significant
because it will provide the first characterization of behavioral manifestations of social touch deficits across
development and investigate the neural circuit disruptions underlying these deficits in mouse models of ASD.
Terms: <0-11 years old><12-20 years old><21+ years old><ASD><Address><Adolescence><Adolescent><Adolescent Youth><Adult><Adult Human><Affective><Age><Air><Allergy><Amygdala><Amygdaloid Body><Amygdaloid Nucleus><Amygdaloid structure><Animal Model><Animal Models and Related Studies><Animals><Area><Assay><Autism><Autistic Disorder><Aversive Stimulus><Behavior><Behavior assessment><Behavioral><Behavioral Assay><Bioassay><Biological Assay><Brain><Brain Nervous System><Brain region><Child><Child Youth><Children (0-21)><Computer Vision Systems><Data><Development><Disease><Disorder><Dysfunction><Early Infantile Autism><Electrophysiology><Electrophysiology (science)><Emotional><Encephalon><Environmental Factor><Environmental Risk Factor><Escalante syndrome><Exhibits><Eye><Eyeball><Facial Expression><Fragile X><Fragile X Syndrome><Functional disorder><Future><Genetic><Genetic predisposing factor><Head><Human><Hypersensitivity><Immune Cell Activation><Impairment><Individual><Infantile Autism><Kanner's Syndrome><Knowledge><Link><Martin-Bell Syndrome><Martin-Bell-Renpenning syndrome><Measures><Mice><Mice Mammals><Microelectrodes><Miniaturized Electrodes><Modeling><Modern Man><Monitor><Motion><Murine><Mus><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neurodevelopmental Disorder><Neurological Development Disorder><Neurons><Neurophysiology / Electrophysiology><Perception><Physiopathology><Polystyrenes><Polystyrol><Problem behavior><QOL><Quality of life><Renpenning syndrome 2><Research><Resolution><Running><Sensory><Si element><Silicon><Social Behavior><Social Controls><Social Interaction><Somatosensory Cortex><Stimulus><System><Tactile><Testing><Touch><Touch sensation><Vibrissae><Whiskers><Work><X-linked mental deficiency-megalotestes syndrome><X-linked mental retardation with fragile X syndrome><X-linked mental retardation-fragile site 1 syndrome><adolescence (12-20)><adulthood><ages><amygdaloid nuclear complex><autism model><autism spectral disorder><autism spectrum disorder><autism-fragile X (AFRAX) syndrome><autistic children><autistic individuals><autistic people><autistic spectrum disorder><avoidance behavior><behavior response><behavioral assessment><behavioral problem><behavioral response><children on the autism spectrum><children with ASD><children with autism><children with autism spectrum disorder><compare to control><comparison control><computer vision><critical period><design><designing><developmental><disease control><disease subgroups><disease subtype><disorder control><disorder subtype><electrophysiological><environmental risk><experience><face expression><fra(X) syndrome><fra(X)(28) syndrome><fra(X)(q27) syndrome><fra(X)(q27-28) syndrome><fragile X-mental retardation syndrome><fragile Xq syndrome><fragile site mental retardation 1><genetic risk factor><immune activation><in vivo><individuals on the autism spectrum><individuals on the spectrum><individuals with ASD><individuals with autism><individuals with autism spectrum disorder><inherited factor><juvenile><juvenile human><kids><machine learned algorithm><machine learning algorithm><machine learning based algorithm><macro-orchidism-marker X (MOMX) syndrome><macro-orchidism-marker X syndrome><maladaptive behavior><mar(X) syndrome><marker X syndrome><mental retardation-macroorchidism syndrome><model of animal><model of autism spectrum disorder><mouse model><murine model><neural><neural circuit><neural circuitry><neurocircuitry><neurodevelopmental disease><neuronal><novel><pathophysiology><people on the autism spectrum><people with ASD><people with autism><people with autism spectrum disorder><perceptual stimulus><physicochemical phenomena related to the senses><postnatal><pre-clinical><preclinical><prevent><preventing><repetitive behavior><resolutions><sensory stimulus><social><social defects><social deficits><social disorders><social dysfunction><social relationships><sociobehavior><sociobehavioral><somatosensory><somesthetic sensory cortex><synaptic circuit><synaptic circuitry><tactile sensation><tactile stimulation><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><youngster>