Glutamate-Induced Degeneration of CA1 Neurons in the Rat Hippocampus Studied by Video Microscopy and Laser Photolysis of a Caged Compound

Abstract

Neurons of the hippocampus die when they are exposed to ischemia. While the detailed mechanism remains unknown, it is widely accepted that glutamate plays a key role in the event of ischemic cell death (Benveniste et al. 1984; Choi 1987; Park et al. 1988; Walestedt et al. 1993). Recently, we have studied glutamate-induced excitotoxicity by observing cortical neurons in primary culture with a video-enhanced contrast differential interference contrast (VEC-DIC) microscope, and found that glutamate induces a rapid change in the fine structure of the nucleus (Ikeda et al. 1996). This observation suggests that glutamate sends an intracellular signal to the nucleus at a very early stage of its excitotoxic action. To obtain more knowledge, we extended the study in different preparations. In this study, by VEC-DIC microscopy, we examined (1) nuclear changes of the neurons induced by glutamate in hippocampal slice culture and (2) morphological changes of dissociated hippocampal neurons elicited by glutamate applied locally to the dendritic region of neurons using a laser photolysis technique. We describe morphological changes of CA1 neurons in both preparations during glutamate stimulation and demonstrate the relationship between the Ca²⁺ signals and degenerative responses in the nucleus.