RT Journal Article
SR Electronic
T1 Altered integration of excitatory inputs onto the basal dendrites of layer 5 pyramidal neurons in a mouse model of Fragile X Syndrome
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.03.14.484306
DO 10.1101/2022.03.14.484306
A1 Diana E. Mitchell
A1 Soledad Miranda-Rottmann
A1 Maxime Blanchard
A1 Roberto Araya
YR 2022
UL http://biorxiv.org/content/early/2022/03/15/2022.03.14.484306.abstract
AB To uncover how synaptic integration of feedforward sensory inputs is affected in autism spectrum disorders (ASD), we used two-photon uncaging of caged glutamate to activate two clustered spines in the basal dendrites of layer 5 (L5) pyramidal neurons from a mouse model of Fragile X syndrome (FXS), the most common genetic cause of ASD. While subthreshold excitatory inputs integrate linearly in wild-type animals, surprisingly those with FXS summate sublinearly, contradicting what would be expected of a hyperexcitable cortex typically associated with ASD. Knockdown of the regulatory β4 subunit of BK channels, rescues the synaptic integration, a result that was corroborated with numerical simulations. Taken together, these findings suggest that there is a differential impairment in the integration of feedforward sensory and feedback predictive inputs in L5 pyramidal neurons in FXS and potentially other forms of ASD. These results challenge the traditional view that FXS and other ASD are characterized by sensory hypersensitivity, but instead by hyposensitivity of sensory inputs and hypersensitivity of predictive inputs onto cortical neurons.Competing Interest StatementThe authors have declared no competing interest.