Atypical excitatory-inhibitory balance in feedforward and feedback circuits in autism
Date
2018
DOI
Authors
Trutzer, Iris
Zikopoulos, Vasileios
Version
Published version
OA Version
Citation
I. Trutzer, V. Zikopoulos. "Atypical excitatory-inhibitory balance in feedforward and feedback circuits in autism." Society for Neuroscience. San Diego, CA, https://www.abstractsonline.com/pp8/#!/4649/presentation/5922.
Abstract
Interactions between excitatory and inhibitory elements in neural circuits are
crucially altered in autism and contribute to its central symptoms. Functionally
and neurochemically distinct classes of inhibitory neurons, which express the
calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV),
are distributed differentially between different cortical areas and cortical
layers. These neurons modify the influence of the excitatory pathways, carried
by myelinated axons, that project to those layers. Excitatory connections that
terminate in the middle or deep cortical layers behave similarly to the
feedforward pathways that are defined in sensory areas, and provide driving
input to the cortex. Pathways that terminate in superficial layers behave as
feedback pathways and modulate the activity of the cortex. In order to study
excitatory-inhibitory balance in the human cortex we studied the distribution
of the three classes of inhibitory neurons and the density of myelinated axons
in post-mortem tissue from medial, cingulate, and lateral prefrontal cortices of
typically developing individuals and individuals with autism. We separately
studied superficial and middle/deep cortical layers in order to distinguish
changes that inuence feedback and feedforward pathways. Adults with
autism had a significant reduction in the density of CR-expressing inhibitory
neurons in both superficial and middle/deep cortical layers in lateral prefrontal
cortices. There was a similar trend in medial prefrontal cortices in adults with
autism. CR-expressing inhibitory neurons in superficial cortical layers serve a
disinhibitory role while those in deep layers may provide modulatory inhibition.
We found no significant change in the density of PV-expressing or CBexpressing
interneurons in adults with autism in these regions. In individuals
with autism there was also a steeper rate of increase in the density of small
myelinated axons, which are representative of short-range pathways, across
layers during development. These parallel structural changes likely produce
opposite functional effects: enhanced short-range feedback pathways
terminate in an environment with increased inhibition, while enhanced shortrange
feedforward pathways terminate in an environment with reduced
inhibition. Together, these changes in laminar structure may significantly affect
information processing in the prefrontal cortex in autism.