title: Diversity of neuropsin (KLK8)-dependent synaptic associativity in the hippocampal pyramidal neuron.
abstract: Hippocampal early (E-) long-term potentiation (LTP) and long-term depression (LTD) elicited by a weak stimulus normally fades within 90 min. Late (L-) LTP and LTD elicited by strong stimuli continue for >180 min and require new protein synthesis to persist. If a strong tetanus is applied once to synaptic inputs, even a weak tetanus applied to another synaptic input can evoke persistent LTP. A synaptic tag is hypothesized to enable the capture of newly synthesized synaptic molecules. This process, referred to as synaptic tagging, is found between not only the same processes (i.e. E- and L-LTP; E- and L-LTD) but also between different processes (i.e. E-LTP and L-LTD; E-LTD and L-LTP) induced at two independent synaptic inputs (cross-tagging). However, the mechanisms of synaptic tag setting remain unclear. In our previous study, we found that synaptic associativity in the hippocampal Schaffer collateral pathway depended on neuropsin (kallikrein-related peptidase 8 or KLK8), a plasticity-related extracellular protease. In the present study, we investigated how neuropsin participates in synaptic tagging and cross-tagging. We report that neuropsin is involved in synaptic tagging during LTP at basal and apical dendritic inputs. Moreover, neuropsin is involved in synaptic tagging and cross-tagging during LTP at apical dendritic inputs via integrin β1 and calcium/calmodulin-dependent protein kinase II signalling. Thus, neuropsin is a candidate molecule for the LTP-specific tag setting and regulates the transformation of E- to L-LTP during both synaptic tagging and cross-tagging.
authors.affiliation: Laboratory of Functional Neuroscience, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, Japan. yishikaw@bs.naist.jp
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Tamura
authors.forename: Sadao
authors.initials: S
authors.lastname: Shiosaka
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods; D019012:Integrin beta1 / Q000378:metabolism; D007610:Kallikreins / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology; D017966:Pyramidal Cells / Q000378:metabolism*; D057057:Serine Proteases / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
chemical_list: D019012:Integrin beta1; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D057057:Serine Proteases; D007610:Kallikreins; C114664:Prss19 protein, mouse