Glutamate-induced delta-catenin redistribution and dissociation from postsynaptic receptor complexes.

Delta-catenin (or neural plakophilin-related arm-repeat protein/neurojungin) is primarily a brain specific member of the p120(ctn) subfamily of armadillo/beta-catenin proteins that play important roles in neuronal development. Our previous studies have shown that the ectopic expression of delta-catenin induces the formation of dendrite-like extensions and that the overexpression of delta-catenin promotes dendritic branching and increases spine density. Here we demonstrate that delta-catenin displays a dendritic distribution pattern in the adult mouse brain and is co-enriched with postsynaptic density-95 (PSD-95) in the detergent insoluble postsynaptic scaffolds. Delta-catenin forms stable complexes with excitatory neurotransmitter receptors including ionotropic N-methyl-D-aspartic acid receptor 2A (NR2A), metabotropic glutamate receptor 1alpha (mGluR1alpha), as well as PSD-95 in vivo. In cultured primary embryonic neurons, delta-catenin clusters co-distribute with filamentous actin and resist detergent extraction. In dissociated hippocampal neurons overexpressing delta-catenin, glutamate stimulation leads to a rapid redistribution of delta-catenin that can be attenuated by 6-cyano-7-nitroquinoxaline-2,3-dione and dizocilpine, selective inhibitors of ionotropic glutamate receptors. Upon glutamate receptor activation, delta-catenin becomes down-regulated and its association with NR2A and mGluR1alpha in cultured neurons is diminished. These findings support a possible functional connection between delta-catenin and the glutamatergic excitatory synaptic signaling pathway during neuronal development.

Fibers immunoreactive for nerve growth factor receptor in adult rat cortex and hippocampus mimic the innervation pattern of AChE-positive fibers.

Numerous reports have indicated that nerve growth factor (NGF) exerts neurotrophic effects on the cholinergic neurons of the basal forebrain. Receptors for NGF (NGFR) have been demonstrated on cholinergic perikarya in the medial septum, diagonal band of Broca, and basal nucleus of Meynert. These neurons provide the major cholinergic innervation to the cerebral cortex and hippocampus, and previous studies have shown that their terminal plexuses also possess NGFR. However, these studies have shown only isolated examples of immunoreactive fibers. In the present paper we confirm and extend the observation of the presence of NGFR immunoreactivity in the hippocampus and cortex of adult rat by showing the entire plexus and demonstrating that the plexus is strikingly similar to the pattern of cholinergic innervation. Fibers stained for acetylcholinesterase (AChE) and NGFR immunoreactivity were found in all layers of the parietal cortex. Within the hippocampus, fibers were observed in all regions, but were most dense in the strata oriens, pyramidale, and radiatum of hippocampal subfields CA1 and CA3. Particularly intense staining was found throughout the dentate gyrus. Partial transections of the fimbria-fornix, which disrupt fibers projecting from the medial septum to the hippocampus, concomitantly abolish the innervation pattern of both NGFR and AChE. These results provide additional evidence that NGFR are associated with septohippocampal and basocortical cholinergic fibers.

Fate of septohippocampal neurons following fimbria-fornix transection: a time course analysis.

Neurons in the medial septum (MS) and vertical limb of the diagonal band (vDB) undergo degenerative changes following transection of their axons. These changes have been well studied by histological techniques such as Nissl stains and immunocytochemistry. A dramatic loss of stained neurons occurs following axotomy and this has been interpreted as indicative of neuronal death. However, since the staining intensity and the size of affected neurons may be reduced by axotomy, it is possible that the apparent neuronal death may actually be due to a decrease in somal size or the ability to detect neurons by routine histological methods. The present study describes the effects of axotomy on MS and vDB neurons which have been labeled by hippocampal injections of the retrograde tracer, Fluoro-Gold (FG), prior to transection of the fimbria-fornix and supracallosal stria. The number of FG-labeled neurons in the MS decreased by 21% at three weeks, 36% at six weeks, and 31% at ten weeks after fimbria-fornix transection. The reduction was statistically significant at 6 and 10 weeks. The number of FG-labeled neurons in the vDB showed no reduction at three weeks but was decreased by 31% and 37% at six and ten weeks, respectively. This was statistically significant only at 10 weeks. By comparison, the number of neurons immunoreactive for choline acetyltransferase (ChAT) was reduced by 75-80% at these time points. The size (area and diameter) of FG-labeled somata decreased in both the MS and vDB within three weeks following fimbria-fornix transection and remained relatively constant at the six- and ten-week time points.(ABSTRACT TRUNCATED AT 250 WORDS)