Altered hippocampal short-term plasticity and associative memory in synaptotagmin IV (-/-) mice.
Synaptotagmin IV (Syt IV) is an activity-inducible, secretory vesicle protein that is thought to function as an inhibitor of neurotransmitter release (Littleton et al. Nature 400:757-760, 1999). To test this hypothesis in neurons of the mammalian CNS, we measured field excitatory postsynaptic potentials (fEPSPs) in hippocampal slice preparations from Syt IV (-/-) mice. At Schaffer collateral synapses, the basal properties of neurotransmission are largely normal. However, two forms of short-term plasticity, paired-pulse facilitation (PPF) and post-tetanic potentiation (PTP), are significantly enhanced in area CA1 of Syt IV (-/-) slices. Similarly, the early stages of long-term potentiation (LTP) are also enhanced at these synapses. Consistent with the low levels of Syt IV observed in dentate granule cells, the mossy fiber synapses in Syt IV (-/-) slices display largely normal PPF and LTP. In addition, we find that Syt IV (-/-) mice have deficits in the associative passive avoidance memory paradigm, but are normal in the novel object recognition paradigm. The synaptic architecture and connectivity of Syt IV (-/-) brains is indistinguishable from wild-type mice as indicated by immunohistochemical analysis. These results suggest Syt IV is a presynaptic negative regulator of short-term plasticity in area CA1 of the hippocampus and is required for some, but not all, forms of hippocampus-dependent memory.
Ferguson
Gregory D
GD
Department of Pharmacology, Box 357750, Health Sciences Building, University of Washington, Seattle, Washington 98195, USA.
Wang
Hongbing
H
Herschman
Harvey R
HR
Storm
Daniel R
DR
D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001362:Avoidance Learning / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D018891:Dentate Gyrus / Q000378:metabolism / Q000503:physiopathology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics*; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics; D050857:Synaptotagmins
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C494293:Syt4 protein, mouse; D050857:Synaptotagmins