Cognitive ability is associated with altered medial frontal cortical circuits in the LgDel mouse model of 22q11.2DS

We established a relationship between cognitive deficits and cortical circuits in the LgDel model of 22q11 Deletion Syndrome (22q11DS)-a genetic syndrome with one of the most significant risks for schizophrenia and autism. In the LgDel mouse, optimal acquisition, execution, and reversal of a visuall...

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Bibliographic Details
Published in:Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2015-05, Vol.25 (5), p.1143-1151
Main Authors: Meechan, D W, Rutz, H L H, Fralish, M S, Maynard, T M, Rothblat, L A, LaMantia, A-S
Format: Article
Language:English
Subjects:
22q11 Deletion Syndrome - pathology
22q11 Deletion Syndrome - psychology
Animals
Behavior, Animal
Cognition
Discrimination Learning
Disease Models, Animal
Executive Function
Frontal Lobe - cytology
Frontal Lobe - pathology
Interneurons - pathology
Male
Mice
Mice, Inbred C57BL
Nerve Net - pathology
Neurons - pathology
Synapses - pathology
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Summary:We established a relationship between cognitive deficits and cortical circuits in the LgDel model of 22q11 Deletion Syndrome (22q11DS)-a genetic syndrome with one of the most significant risks for schizophrenia and autism. In the LgDel mouse, optimal acquisition, execution, and reversal of a visually guided discrimination task, comparable to executive function tasks in primates including humans, are compromised; however, there is significant individual variation in degree of impairment. The task relies critically on the integrity of circuits in medial anterior frontal cortical regions. Accordingly, we analyzed neuronal changes that reflect previously defined 22q11DS-related alterations of cortical development in the medial anterior frontal cortex of the behaviorally characterized LgDel mice. Interneuron placement, synapse distribution, and projection neuron frequency are altered in this region. The magnitude of one of these changes, layer 2/3 projection neuron frequency, is a robust predictor of behavioral performance: it is substantially and selectively lower in animals with the most significant behavioral deficits. These results parallel correlations of volume reduction and altered connectivity in comparable cortical regions with diminished executive function in 22q11DS patients. Apparently, 22q11 deletion alters behaviorally relevant circuits in a distinct cortical region that are essential for cognitive function.
ISSN:1047-3211
1460-2199
DOI:10.1093/cercor/bht308