Integrin β3 regulates apical dendritic morphology of pyramidal neurons throughout hippocampal CA3

Author:

Handwerk Christopher J.1,Denzler Collin J.1,Kalinowski Anna R.1,Cook Hollyn N.1,Rodriguez Hilda V.1,Bland Katherine M.1,Brett Cooper A.1,Swinehart Brian D.1,Vinson Elizabeth C.1,Vidal George S.1ORCID

Affiliation:

1. Department of Biology James Madison University MSC 7801, Harrisonburg Virginia 22807 USA

Abstract

AbstractIn excitatory hippocampal pyramidal neurons, integrin β3 is critical for synaptic maturation and plasticity in vitro. Itgb3 is a potential autism susceptibility gene that regulates dendritic morphology in the cerebral cortex in a cell‐specific manner. However, it is unknown what role Itgb3 could have in regulating hippocampal pyramidal dendritic morphology in vivo, a key feature that is aberrant in many forms of autism and intellectual disability. We found that Itgb3 mRNA is expressed in the stratum pyramidale of CA3. We examined the apical dendritic morphology of CA3 hippocampal pyramidal neurons in conditional Itgb3 knockouts and controls, utilizing the Thy1‐GFP‐M line. We fully reconstructed the apical dendrite of each neuron and determined each neuron's precise location along the dorsoventral, proximodistal, and radial axes of the stratum pyramidale. We found a very strong effect for Itgb3 expression on CA3 apical dendritic morphology: neurons from conditional Itgb3 knockouts had longer and thinner apical dendrites than controls, particularly in higher branch orders. We also assessed potential relationships between pairs of topographic or morphological variables, finding that most variable pairs were free from any linear relationships to each other. We also found that some neurons from controls, but not conditional Itgb3 knockouts, had a graded pattern of overall diameter along the dorsoventral and proximodistal axes of the stratum pyramidale of CA3. Taken together, Itgb3 is essential for constructing normal dendritic morphology in pyramidal neurons throughout CA3.

Funder

National Institute of Neurological Disorders and Stroke

Publisher

Wiley

Subject

Cognitive Neuroscience

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