Separating kindling and LTP: lessons from studies of PKM zeta in developing and adult rats.
The kindling model of temporal lobe epilepsy (TLE) and the memory model of long-term potentiation (LTP) may have common underlying mechanisms. This is evident by the demonstration that certain signaling molecules play a key role in both. Recently, a brain specific isoform of protein kinase C (PKMzeta) has been shown to play a significant role in both maintaining LTP and memory storage. We were interested in determining if this kinase had a crossover role in kindling-induced epileptogenesis. Using developing and adult rats we examined the role of PKMzeta in kindling. In developing (P15) rats we determined the effect of PKMzeta on retention of amygdala kindling and kindling rate by intra-amygdala administration of a selective PKMzeta antagonist, ZIP (10 nmol). In adult rats we examined the effect of PKMzeta inhibition, ZIP (10 nmol), on after discharge (AD) thresholds and kindling retention using rapid hippocampal kindling. Inhibition of PKMzeta by the antagonist ZIP did not affect kindling rate or retention in developing rats. In addition there was also no observed effect on AD thresholds and kindling retention in adult rats. Our results show that, despite the similarities between kindling and LTP in their induction, there is dissociation in the role that PKMzeta plays within the two in maintenance. This may be of importance in establishing a separation between the pathophysiological processes involved in sustaining kindling and the physiological mechanisms involved in maintaining LTP and memory storage.
Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, The Montefiore/Einstein Epilepsy, Center, Albert Einstein College of Medicine, Bronx, NY, USA. heida@medicine.tamhsc.edu
James G
JG
Heida
Dario J
DJ
Englot
Todd C
TC
Sacktor
Hal
H
Blumenfeld
Solomon L
SL
Moshé
D000367:Age Factors; D000818:Animals; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D007696:Kindling, Neurologic; D017774:Long-Term Potentiation; D008297:Male; D010455:Peptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology
D007527:Isoenzymes; D010455:Peptides; D011493:Protein Kinase C; C504730:protein kinase M zeta, rat