Altered hippocampal short-term plasticity and associative memory in synaptotagmin IV (-/-) mice

Hippocampus. 2004;14(8):964-74. doi: 10.1002/hipo.20013.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Association Learning / physiology*
  • Avoidance Learning / physiology
  • Calcium-Binding Proteins / deficiency
  • Calcium-Binding Proteins / genetics*
  • Dentate Gyrus / metabolism
  • Dentate Gyrus / physiopathology
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials / genetics
  • Hippocampus / metabolism
  • Hippocampus / physiopathology*
  • Long-Term Potentiation / genetics
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics*
  • Memory Disorders / genetics
  • Memory Disorders / metabolism
  • Memory Disorders / physiopathology
  • Memory, Short-Term / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mossy Fibers, Hippocampal / metabolism
  • Mossy Fibers, Hippocampal / physiopathology
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics*
  • Neuronal Plasticity / genetics*
  • Organ Culture Techniques
  • Presynaptic Terminals / metabolism*
  • Synaptic Transmission / genetics
  • Synaptotagmins


  • Calcium-Binding Proteins
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Syt4 protein, mouse
  • Synaptotagmins