Protein kinase C and F1/GAP-43 gene expression in hippocampus inversely related to synaptic enhancement lasting 3 days.
The mRNA levels of protein F1 (also known as GAP-43), and protein kinase C (PKC) subtypes were measured 3 days after the induction of long-term enhancement (also known as long-term potentiation) in the hippocampus of chronically prepared conscious rats by quantitative in situ hybridization. Altered mRNA levels correlated significantly with alternations in synaptic efficacy; such correlations have not been reported previously. Rats with greater synaptic enhancement had lower gene expression in the CA3 subfield of F1/GAP-43 and both beta-PKC and gamma-PKC, but not alpha-PKC. For microtubule-associated protein 2 (MAP-2), neurogranin, and the glutamate receptor subtype B-flip, no correlation was observed in any cell field between synaptic enhancement and hybridization to the mRNA. To our surprise, alterations in mRNA levels of F1/GAP-43 and gamma-PKC were highly correlated (r = +0.928, P < 0.001), suggesting coordinate regulation. Since F1/GAP-43 is associated with neurite growth, its lowered expression at 3 days would reduce potential growth, leading to synaptic stabilization. We propose that long-term synaptic change is mediated by gene expression of the very same proteins initially modified posttranslationally.
Meberg
P J
PJ
Department of Psychology, Northwestern University, Evanston, IL 60208.
Barnes
C A
CA
McNaughton
B L
BL
Routtenberg
A
A
D000818:Animals; D005071:Evoked Potentials; D019922:GAP-43 Protein; D015870:Gene Expression; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology; D017403:In Situ Hybridization; D017774:Long-Term Potentiation; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D010750:Phosphoproteins / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000096:biosynthesis*; D011712:Pyramidal Tracts / Q000378:metabolism; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000502:physiology*; D013997:Time Factors
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D015347:RNA Probes; D012333:RNA, Messenger; D011493:Protein Kinase C