Protein phosphatase-1 regulation in the induction of long-term potentiation: heterogeneous molecular mechanisms.
Protein phosphatase inhibitor-1 (I-1) has been proposed as a regulatory element in the signal transduction cascade that couples postsynaptic calcium influx to long-term changes in synaptic strength. We have evaluated this model using mice lacking I-1. Recordings made in slices prepared from mutant animals and also in anesthetized mutant animals indicated that long-term potentiation (LTP) is deficient at perforant path-dentate granule cell synapses. In vitro, this deficit was restricted to synapses of the lateral perforant path. LTP at Schaffer collateral-CA1 pyramidal cell synapses remained normal. Thus, protein phosphatase-1-mediated regulation of NMDA receptor-dependent synaptic plasticity involves heterogeneous molecular mechanisms, in both different dendritic subregions and different neuronal subtypes. Examination of the performance of I-1 mutants in spatial learning tests indicated that intact LTP at lateral perforant path-granule cell synapses is either redundant or is not involved in this form of learning.
Allen
P B
PB
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA. allenp@rickvax.rockefeller.edu
Hvalby
O
O
Jensen
V
V
Errington
M L
ML
Ramsay
M
M
Chaudhry
F A
FA
Bliss
T V
TV
Storm-Mathisen
J
J
Morris
R G
RG
Andersen
P
P
Greengard
P
P
D000818:Animals; D002352:Carrier Proteins; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009473:Neuronal Plasticity / Q000235:genetics*; D019580:Perforant Pathway / Q000166:cytology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D054645:Protein Phosphatase 1; D017966:Pyramidal Cells / Q000737:chemistry / Q000201:enzymology; D016601:RNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D013028:Space Perception / Q000502:physiology; D013569:Synapses / Q000737:chemistry / Q000201:enzymology; D014867:Water
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; C021042:protein phosphatase inhibitor-1; D014867:Water; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1