Impaired hippocampal long-term potentiation in microtubule-associated protein 1B-deficient mice.
Microtubule-associated protein (MAP)1B-heterozygous (MAP1B+/-) mice are deficient in the expression of MAP1B in the hippocampus, cerebellum, and olfactory cortex. Although MAP1B+/- mice showed half the normal levels of MAP1B protein, they had no measurable amounts of phosphorylated MAP1B. High-frequency theta burst stimulation of Schaffer collateral-CA1 axons in hippocampal slices from MAP1B+/- mice elicited long-term potentiation (LTP) that decayed rapidly to baseline, in contrast to the non-decremental LTP exhibited by age-matched wild-type slices. A separate group of MAP1B+/- and wild-type slices was examined for a longer time course of 3 hr post-tetanus in response to multiple high-frequency stimulus trains that induced saturated LTP. MAP1B+/- slices showed marked reductions in both immediate post-tetanic potentiation and LTP that decayed much more rapidly than that in wild-type slices. The induction of LTP was associated with a rapid dephosphorylation of MAP1B within 5-15 min post-tetanus, suggesting that the normal expression of MAP1B and conversion to a dephosphorylated state may be a cellular mediator of cytoskeletal alterations necessary for long-term activity-dependent synaptic plasticity.
Zervas
Mark
M
Skirball Institute, New York University School of Medicine, New York, USA.
Opitz
Thoralf
T
Edelmann
Winfried
W
Wainer
Bruce
B
Kucherlapati
Raju
R
Stanton
Patric K
PK
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000293:injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000502:physiology; D010766:Phosphorylation; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D013997:Time Factors
D008869:Microtubule-Associated Proteins; C085284:microtubule-associated protein 1B