CALCIUM: A Role for Neuroprotection and Sustained Adaptation

GluR2_Bknockdown produces age-depenedent epileptogenicity and neurodegeneration. A.³³P GluR2_B antisense deoxyoligonucleotides (AS-ODN) autoradiography showed the spread and accumulation of our GluR2_B antisense injection was limited to the dorsal ipsilateral hippocampus, as indicated by schematic outline of a radiolabeled coronal section. B. In adults, following knockdown of GluR2_B expression in the hippocampus alone, EEG recordings showed typical asynchronous activity and normal movement artifacts (upper left trace). Similarly, GluR2_B knockdown followed by KA injection did not alter the rhythmical activity in the EEG when compared to KA controls (bottom left trace). In pups, GluR2_B knockdown in the absence of KA, produced spontaneous convulsive seizure-like behavior, including body tonus with fore-limb extension and laying on one side; this behavior was associated with high-frequency low-amplitude rhythmical activity of increasing size. Large movement artifacts shown represent intermittent bilateral jerking movements (asterisks) (upper right trace). In GluR2_B AS-ODN–treated pups lacking the phenotypic behavior (bottom right trace), a low concentration of KA produced high-frequency rhythmical oscillations associated with tonic-clonic seizure behavior. C. As predicted by the procedure, after GluR2_B knockdown and KA-induced seizures, GluR2_B mRNA expression was unaltered in CA1 and DG regions but was decreased or lost only within regions of CA3 cell loss at either age [between the arrows in panel (C) and at the arrow in panel (F)]. D. There was a population spike (recruitment of firing) over the excitatory postsynaptic potential (EPSP) after GluR2_B expression knockdown compared to that observed in sense-ODN–treated controls (1, baseline; 2, 100 Hz tetanic stimulation; 3, post-tetanus response). E. Long-term potentiation (LTP) was attenuated (3) after GluR2_B knockdown where as the induction was unaltered (2). Modified from (75, 76, 142). Reprinted with permission.