Format

Send to

Choose Destination
Neuron. 2019 Aug 21;103(4):673-685.e5. doi: 10.1016/j.neuron.2019.05.037. Epub 2019 Jun 20.

The Autism-Associated Gene Scn2a Contributes to Dendritic Excitability and Synaptic Function in the Prefrontal Cortex.

Author information

1
Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
2
Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.
3
Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: kevin.bender@ucsf.edu.

Abstract

Autism spectrum disorder (ASD) is strongly associated with de novo gene mutations. One of the most commonly affected genes is SCN2A. ASD-associated SCN2A mutations impair the encoded protein NaV1.2, a sodium channel important for action potential initiation and propagation in developing excitatory cortical neurons. The link between an axonal sodium channel and ASD, a disorder typically attributed to synaptic or transcriptional dysfunction, is unclear. Here we show that NaV1.2 is unexpectedly critical for dendritic excitability and synaptic function in mature pyramidal neurons in addition to regulating early developmental axonal excitability. NaV1.2 loss reduced action potential backpropagation into dendrites, impairing synaptic plasticity and synaptic strength, even when NaV1.2 expression was disrupted in a cell-autonomous fashion late in development. These results reveal a novel dendritic function for NaV1.2, providing insight into cellular mechanisms probably underlying circuit and behavioral dysfunction in ASD.

KEYWORDS:

2-photon imaging; NaV1.2; Scn2a; action potential backpropagation; autism spectrum disorder; dendritic excitability; electrophysiology; haploinsufficiency; intellectual disability; sodium channel; synaptic plasticity

PMID:
31230762
DOI:
10.1016/j.neuron.2019.05.037
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center