Amygdala kindling-induced seizures selectively impair spatial memory. 1. Behavioral characteristics and effects on hippocampal neuronal protein kinase C isoforms.
Protein kinase C (PKC) comprises a family of kinases consisting of nine subspecies that are differentially distributed in the central nervous system. This implies distinct functions. Its involvement is suggested in cellular and molecular mechanisms by which the hippocampus exerts influence on information processing. In this study, it was questioned whether abnormal activity in the neuronal substrate, particularly the hippocampal formation, induced by amygdala kindling indeed impairs spatial memory performance and correlated alpha, beta I/II, and gamma PKC subspecies expression. Rats were trained in a spatial discrimination task (SDT) and simultaneously kindled in the amygdala to induce abnormal, epileptiform activity. Control rats were only trained in the holeboard, a "free choice" maze, in which working (WM) and reference memory (RM) were simultaneously examined. Halfway through and at the end of the experiments the influence of kindling and SDT training on the immunoreactivity for PKC subspecies alpha, beta I/II, and gamma was evaluated in the hippocampal formation. Kindling resulted in a gradual increase in afterdischarge duration and motor seizure (MS) severity. Repeated SDT training ultimately resulted in an asymptotic level of WM and RM performance. As soon as generalized MSs developed, kindled rats failed to improve RM, whereas WM was not influenced. Compared to untrained rats, in trained controls PKC gamma but not PKC alpha beta I/II immunoreactivity was elevated in CA1 pyramidal and dentate gyrus granular cells. Generalized but not partial MSs abolished these alterations in PKC gamma immunoreactivity. The present data indicate that repeated training in a SDT affects the expression of PKC subspecies gamma but not of alpha or beta in the rat hippocampus. Generalized epileptiform activity impair both acquisition of new spatial RM information and PKC gamma expression. It is argued that PKC gamma plays a role in cellular mechanisms through which pathological brain activity impairs certain aspects of spatial memory.
Beldhuis
H J
HJ
Department of Animal Physiology, University of Groningen, Haren, The Netherlands.
Everts
H G
HG
Van der Zee
E A
EA
Luiten
P G
PG
Bohus
B
B
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D004193:Discrimination Learning / Q000502:physiology*; D006624:Hippocampus / Q000201:enzymology*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D007696:Kindling, Neurologic; D008297:Male; D008568:Memory / Q000502:physiology*; D015999:Multivariate Analysis; D009474:Neurons / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000503:physiopathology*; D013028:Space Perception / Q000502:physiology*
D007527:Isoenzymes; D011493:Protein Kinase C