Synaptic abnormalities in the infralimbic cortex of a model of congenital depression.
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 infralimbic 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 immunolabeling intensities were substantially lower in cLH rats, as were numerical densities of synapse-sized clusters of the AMPA receptor subunit GluA1. Similar but less pronounced differences (comparable numerical densities but reduced immunolabeling intensity for PSD95) were found in the somatosensory cortex. In contrast, non-helpless rats had 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 GABAergic contacts. These results indicate that congenital tendencies that increase or decrease depression-like behavior differentially affect excitatory synapses.
Department of Anatomy and Neurobiology, University of California, Irvine, California 92697, USA.
Ronald R
RR
Seese
Lulu Y
LY
Chen
Conor D
CD
Cox
Daniela
D
Schulz
Alex H
AH
Babayan
William E
WE
Bunney
Fritz A
FA
Henn
Christine M
CM
Gall
Gary
G
Lynch
D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology*; D003865:Major Depressive Disorder / Q000473:pathology*; D004195:Disease Models, Animal; D006380:Helplessness, Learned; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000473:pathology*