Enhanced hippocampal long-term potentiation in mice lacking heparin-binding growth-associated molecule.
Heparin-binding growth-associated molecule (HB-GAM) (pleiotrophin) is a highly conserved extracellular matrix-associated protein implicated in a diverse range of developmental processes, including the formation and plasticity of neuronal connections. Using gene targeting, we have in the present study created HB-GAM-deficient mice that are viable and fertile and show no gross anatomical abnormalities. The hippocampal structure as well as basal excitatory synaptic transmission in the area CA1 appear normal in the mice lacking HB-GAM. However, hippocampal slices from HB-GAM-deficient mice display a lowered threshold for induction of long-term potentiation (LTP), which reverts back to the wild-type level by application of HB-GAM. HB-GAM expression in hippocampus is activity-dependent and upregulated in several neuropathological conditions. Thus, we suggest that HB-GAM acts as an inducible signal to inhibit LTP in hippocampus.
Amet
L E
LE
Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08540, USA.
Lauri
S E
SE
Hienola
A
A
Croll
S D
SD
Lu
Y
Y
Levorse
J M
JM
Prabhakaran
B
B
Taira
T
T
Rauvala
H
H
Vogt
T F
TF
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics*; D016207:Cytokines / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D018390:Gene Targeting; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
D002352:Carrier Proteins; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; D011994:Recombinant Proteins; C066845:pleiotrophin