Boundary conditions for the maintenance of memory by PKMzeta in neocortex.
We report here that ZIP, a selective inhibitor of the atypical protein kinase C isoform PKMzeta, abolishes very long-term conditioned taste aversion (CTA) associations in the insular cortex of the behaving rat, at least 3 mo after encoding. The effect of ZIP is not replicated by a general serine/threonine protein kinase inhibitor that is relatively ineffective toward PKMzeta, is independent of the intensity of training and the perceptual quality of the taste saccharin (conditioned stimulus, CS), and does not affect the ability of the insular cortex to re-encode the same specific CTA association again. The memory trace is, however, insensitive to ZIP during or immediately after training. This implies that the experience-dependent cellular plasticity mechanism targeted by ZIP is established following a brief time window after encoding, consistent with the standard period of cellular consolidation, but then, once established, does not consolidate further to gain immunity to the amnesic agent. Hence, we conclude that PKMzeta is not involved in short-term CTA memory, but is a critical component of the cortical machinery that stores long- and very long-term CTA memories.
Shema
Reut
R
Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Hazvi
Shoshi
S
Sacktor
Todd C
TC
Dudai
Yadin
Y
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000502:physiology*; D008845:Microinjections; D019579:Neocortex / Q000201:enzymology* / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D013649:Taste / Q000187:drug effects; D000099221:Protein Kinase C zeta
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D000099221:Protein Kinase C zeta; C529317:myristoyl-SIYRRGARRWRKL