<p id="P3">Loss-of-function mutations in CNTNAP2 cause a syndromic form of autism
spectrum disorder
in humans and produce social deficits, repetitive behaviors, and seizures in mice.
However, the functional effects of these mutations at cellular and circuit levels
remain elusive. Using laser-scanning photostimulation, whole-cell recordings, and
electron microscopy, we found a dramatic decrease in excitatory and inhibitory synaptic
inputs onto L2/3 pyramidal neurons of the medial prefrontal cortex (mPFC) of Cntnap2
knockout (KO) mice, concurrent with reduced spines and synapses, despite normal dendritic
complexity and intrinsic excitability. Moreover, recording of mPFC local field potentials
(LFPs) and unit spiking
<i>in vivo</i> revealed increased activity in inhibitory neurons, reduced phase-locking
to delta
and theta oscillations, and delayed phase preference during locomotion. Excitatory
neurons showed similar phase modulation changes at delta frequencies. Finally, pairwise
correlations increased during immobility in KO mice. Thus, reduced synaptic inputs
can yield perturbed temporal coordination of neuronal firing in cortical ensembles.
</p><p id="P4">Lazaro et al. demonstrate a decrease in synaptic inputs onto mPFC L2/3
pyramidal neurons
of Cntnap2 KO mice, concurrent with reduced spines and synapses. These lead to perturbed
network activity, with mPFC cells exhibiting reduced phase locking and altered preferred
phases to slow LFP oscillations, which may underlie autism-related phenotypes.
</p><p id="P5">
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