Septal cholinergic deafferentation of the dentate gyrus results in a loss of a subset of neuropeptide Y somata and an increase in synaptic area on remaining neuropeptide Y dendrites.

Removal of cholinergic septal inputs using the immunotoxin 192 IgG-saporin reduces the number of interneurons containing neuropeptide Y (NPY)-immunoreactivity in the rat dentate gyrus by approximately 30% [Milner et al., J. Comp. Neurol. 386 (1997) 48-59]. The goal of the present study was to determine if NPY-containing neurons that survive deafferentation have any distinguishing morphological and/or microenvironmental features. For this, 2 or 24 weeks after intracerebroventricular injections of 192 IgG-saporin, NPY-immunolabeled neurons in the hilus of the dentate gyrus were examined by electron microscopy. Neither the size nor morphological traits of NPY-labeled perikaryal or dendritic profiles from lesioned compared to control rats at either time-point differed significantly. However, at both time-points, NPY-containing somatal profiles from immunolesioned rats compared to controls had a reduced percentage of their plasmalemmal surface apposed to unmyelinated axon profiles and an increased percentage of their surface occupied by astrocytic profiles. At the 24 week time-point, these differences were statistically significant. The primary contributing factor for these changes was the absence of a subgroup of NPY-labeled somatal profiles in lesioned rats compared to controls which was: (a) distinguished by frequent appositions of unmyelinated axons (from 15 to 35%) to the plasmalemmal surface; and (b) located primarily in the central hilar region. Unlike NPY-containing somata, changes associated with NPY-labeled dendritic profiles were exclusively related to associated presynaptic profiles at the 24 week time-point. In lesioned rats compared to controls at this time-point, NPY-containing dendritic profiles had a concurrent increase in the percentage of the plasmalemmal surface occupied by active zones and the size of terminals contacting them. The present results combined with those of our earlier study suggest that septal cholinergic deafferentation results in: (a) the loss of a distinct subpopulation of hippocampal NPY-containing neurons; and (b) an increase in total active zone area suggesting a strengthening of synaptic connections to the surviving population of NPY-containing neurons in the long term. Copyright 1999 Elsevier Science B.V.