The regulatory role of heparanase of synaptic plasticity in hippocampus

Abstract

Long-term potentiation (LTP) is one of the major cellular mechanisms that underlie learning and memory. Perineuronal heparan sulfate (HS) moieties are implicated in the control of the open-state of membrane channels for maintenance of synaptic strength. LTP in the hippocampus was shown to be perturbed by bath treatment of hippocampal slices with bacterial heparinase III but baseline synaptic transmission was not affected. Our finding of neuronal heparanase at the CA1 hippocampal neurons led us to hypothesize that heparanase is the mammalian counterpart that regulates synaptic plasticity by modulating peri-synaptic HS level. Heparanase is synthesized as a pro-form which undergoes proteolytic activation to become the mature form. To address the hypothesis, we prepared recombinant products of both pro- and mature forms of rat heparanase and tested their effects on synaptic strength in the Schaffer collateral pathway of hippocampal slices. We found that treatment with recombinant pro-heparanase diminished basal synaptic strength as well as LTP. The results support our hypothesis and further suggest proheparanase involvement in the downregulation of glutamate receptors at the synapse. This work will be consolidated by further studies with mature heparanase derived from the recombinant product. [Supported by HKRGC 774608]