Balance of excitation and inhibition in orbitofrontal cortex and potential for disruption in autism
Date
2018
DOI
Authors
Liu, Xuefend
Bautista, Julied
Liu, Edward
Zikopoulos, Vasileios
Version
Published version
OA Version
Citation
X. Liu, J. Bautista, E. Liu, V. Zikopoulos. "Balance of excitation and inhibition in orbitofrontal cortex and potential for disruption in autism." Society for Neuroscience. San Diego, CA, 2018-11-06 - 2018-11-06. https://www.abstractsonline.com/pp8/#!/4649/presentation/5921.
Abstract
The human orbitofrontal cortex (OFC) is involved in assessing the emotional
significance of events and stimuli, emotion based learning, allocation of
attentional resources, and social cognition. Little is known about the structure,
connectivity and excitatory/inhibitory circuit interactions underlying these
diverse functions in human OFC. To fill this gap we used high resolution
microscopy, followed by quantitative tracing analysis, to characterize the
morphology and distribution of myelinated axons across cortical layers in
human OFC at the single axon level, as a proxy of excitatory pathways. In the
same regions, we also examined the laminar distribution of neurochemically- and
functionally-distinct inhibitory neurons that express calcium-binding
proteins parvalbumin (PV), calbindin (CB), and calretinin (CR). Associations of
myelinated axons with distinct inhibitory neurons changed across layers and
provided a proxy for the study of the excitatory/inhibitory ratio in OFC. We
found that density of myelinated axons increased consistently towards layer VI,
while average axon diameter did not change significantly. Inhibitory CR-positive
neurons were mostly found in layer II, the layer with the lowest density of
myelinated axons. CB-positive inhibitory neurons were most dense in layer II
and upper layer III. PV-positive inhibitory neurons were mostly found in the
middle/deep layers, especially lower layer III, among a dense plexus of
myelinated axons, some of which also expressed PV, presumably coming from
the thalamus. The balance between excitation and inhibition in OFC is at the
core of OFC function. The OFC gets an overview of the sensory environment
through feedforward cortical inputs and assesses the emotional significance of
events, based on robust feedback input from the amygdala, in processes that
are disrupted in autism spectrum disorder (ASD). We previously showed that in
individuals with ASD, excitatory OFC pathways exhibit overall thinning of the
myelin sheath of axons, which likely affects conduction velocity and
neurotransmission. This suggests laminar-specific changes in the ratio of
excitation/inhibition in OFC of individuals with ASD, and may provide the
anatomic basis for disrupted transmission of signals for emotions.