EN
Cognitive processes such as learning and memory require functional modifications within neural circuits which involve reorganization of existing synaptic connections and modulation of its strength. In addition, neurons can significantly enhance information storage capacity by scaling dendritic and somatic excitability (e.g. EPSP-to-spike potentiation). Proteolysis of extracellular matrix constituents and membrane proteins by matrix metalloproteases (MMP) has recently emerged as a key element in these processes. We identified NMDARs as a target for MMP-3 but not MMP-2/9 immediately following LTP induction. We next applied confocal imaging for nuclear cFos protein in brain slices fixed immediately following electrophysiology studies and Ca2+ imaging for somatodendritic NMDAR-mediated Ca2+ waves. We concluded that long-term hippocampal E-S potentiation limited to stratum radiatum inputs required MMP-3 activity in a narrow time window following enhanced neuronal activity that promotes NMDAR-mediated postsynaptic Ca2+ entry and activation of downstream signaling cascades leading to immediate early genes transcription. Most recently we discovered that in striking contrast to apical dendrites, synaptic plasticity induced at basal dendrites was insensitive to a wide range of broad and subtype specific MMP inhibitors. Thus, stratum radiatum synapses required MMP-3, alpha 5-integrins or protease-activated receptor 1 (PAR-1) and PKC kinase activity for modulation of NMDARs function, unlike stratum oriens synapses. FINANCIAL SUPPORT: National Science Center grant no. SONATA/2014/13/D/NZ4/03045.