Altered brain-wide auditory networks in fmr1-mutant larval zebrafish

Altered sensory processing is characteristic of several psychiatric conditions, including autism and fragile X syndrome (FXS). Here, we use whole-brain calcium imaging at cellular resolution to map sensory processing in wild type larval zebrafish and mutants for fmr1, which causes FXS in humans. Using functional analyses and graph theory, we describe increased transmission and reduced filtering of auditory information, resulting in network-wide hypersensitivity analogous to the auditory phenotypes seen in FXS.

[1]  Ethan K. Scott,et al.  A profile of auditory‐responsive neurons in the larval zebrafish brain , 2017, The Journal of comparative neurology.

[2]  Ethan K. Scott,et al.  Cellular-Resolution Imaging of Vestibular Processing across the Larval Zebrafish Brain , 2018, Current Biology.

[3]  W. Kaufmann,et al.  Autism spectrum disorder in fragile X syndrome: Communication, social interaction, and specific behaviors , 2004, American journal of medical genetics. Part A.

[4]  K. R. Ridderinkhof,et al.  Auditory change detection in fragile X syndrome males: A brain potential study , 2012, Clinical Neurophysiology.

[5]  Ethan K. Scott,et al.  Diffuse light‐sheet microscopy for stripe‐free calcium imaging of neural populations , 2018, Journal of biophotonics.

[6]  Stefan R. Pulver,et al.  Ultra-sensitive fluorescent proteins for imaging neuronal activity , 2013, Nature.

[7]  Caroline E. Robertson,et al.  Sensory perception in autism , 2017, Nature Reviews Neuroscience.

[8]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[9]  Faraz Farzin,et al.  Dynamic Object Representations in Infants with and without Fragile X Syndrome , 2009, Front. Hum. Neurosci..

[10]  É. Khandjian,et al.  Prevalence of carriers of premutation-size alleles of the FMRI gene--and implications for the population genetics of the fragile X syndrome. , 1995, American journal of human genetics.

[11]  Charles J. Lynch,et al.  Salience network-based classification and prediction of symptom severity in children with autism. , 2013, JAMA psychiatry.

[12]  T. Mueller.  What is the Thalamus in Zebrafish? , 2012, Front. Neurosci..

[13]  C. Keysers,et al.  Increased Functional Connectivity Between Subcortical and Cortical Resting-State Networks in Autism Spectrum Disorder. , 2015, JAMA psychiatry.

[14]  E. Pnevmatikakis,et al.  NoRMCorre: An online algorithm for piecewise rigid motion correction of calcium imaging data , 2017, Journal of Neuroscience Methods.

[15]  M. J. den Broeder,et al.  Generation and Characterization of Fmr1 Knockout Zebrafish , 2009, PloS one.

[16]  J. Tiago Gonçalves,et al.  Circuit level defects in the developing neocortex of fragile X mice , 2013, Nature Neuroscience.

[17]  James E. Fitzgerald,et al.  Whole-brain activity mapping onto a zebrafish brain atlas , 2015, Nature Methods.

[18]  A fast cholinergic modulation of the primary acoustic startle circuit in rats , 2013, Brain Structure and Function.

[19]  J. Faubert,et al.  Integrative cortical dysfunction and pervasive motion perception deficit in fragile X syndrome , 2004, Neurology.

[20]  S. Siegel,et al.  Sensory processing in autism spectrum disorders and Fragile X syndrome—From the clinic to animal models , 2017, Neuroscience & Biobehavioral Reviews.

[21]  K. Lu,et al.  Behavioral and Synaptic Circuit Features in a Zebrafish Model of Fragile X Syndrome , 2013, PloS one.

[22]  Daniel P. Kennedy,et al.  The Autism Brain Imaging Data Exchange: Towards Large-Scale Evaluation of the Intrinsic Brain Architecture in Autism , 2013, Molecular Psychiatry.

[23]  K. Mullen,et al.  Differential impact of the FMR1 gene on visual processing in fragile X syndrome. , 2003, Brain : a journal of neurology.

[24]  I. Tarkka,et al.  Augmentation of Auditory N1 in Children with Fragile X Syndrome , 2004, Brain Topography.