Synaptic abnormalities in the infralimbic cortex of a model of congenital depression

Abstract

Multiple lines of evidence suggest that disturbances in excitatory transmission contribute to depression. Whether these defects involve the number, size, or composition of glutamatergic contacts is unclear. This study used recently introduced procedures for fluorescence deconvolution tomography in a well-studied rat model of congenital depression to characterize excitatory synapses in layer I of infra-limbic cortex, a region involved in mood disorders, and of primary somatosensory cortex. Three groups were studied: (1) rats bred for learned helplessness (cLH); (2) rats resistant to learned helplessness (cNLH); and (3) control Sprague Dawley rats. In fields within infralimbic cortex, cLH rats had the same numerical density of synapses, immunolabeled for either the postsynaptic density (PSD) marker PSD95 or the presynaptic protein synaptophysin, as controls. However, PSD95 immuno labeling intensities were substantially lowerinc LHrats, as we renumerical densities of synapse-sized clusters of the AMPA receptor sub unit GluA1. Similar but less pronounced differences (comparable numerical densities but reduced immuno labeling intensity for PSD95) were found in the somato sensory cortex. In contrast, non-helpless ratshad 25% more PSDs than either cLH or control rats without any increase in synaptophysin-labeled terminal frequency. Compared with controls, both cLH and cNLH rats had fewer GAB Aergic contacts. These results indicate that congenital tendencies that increase or decrease depression-like behavior differentially affect excitatory synapses. © 2013 the authors.