The effect of pharmacological inhibition of Serine Proteases on neuronal networks in vitro

PeerJ. 2019 Apr 23;7:e6796. doi: 10.7717/peerj.6796. eCollection 2019.

Abstract

Neurons are embedded in an extracellular matrix (ECM), which functions both as a scaffold and as a regulator of neuronal function. The ECM is in turn dynamically altered through the action of serine proteases, which break down its constituents. This pathway has been implicated in the regulation of synaptic plasticity and of neuronal intrinsic excitability. In this study, we determined the short-term effects of interfering with proteolytic processes in the ECM, with a newly developed serine protease inhibitor. We monitored the spontaneous electrophysiological activity of in vitro primary rat cortical cultures, using microelectrode arrays. While pharmacological inhibition at a low dosage had no significant effect, at elevated concentrations it altered significantly network synchronization and functional connectivity but left unaltered single-cell electrical properties. These results suggest that serine protease inhibition affects synaptic properties, likely through its actions on the ECM.

Keywords: Cortex; Electrophysiology; Extracellular matrix; Microelectrode arrays; Network activity; Neurobiology; Neurons; Patch-clamp; Serine proteases; Synaptic connectivity.

Associated data

  • figshare/10.6084/m9.figshare.5873685.v2

Grant support

This work was supported by the European Union’s Framework Programme for Research and Innovation (under the H2020 ETN grant n. 642881 to Stefanie Dedeurwaerdere, Pieter Van Der Veken, and Koen Augustyns; under the Specific Grant Agreement n. 785907 - Human Brain Project to Michele Giugliano; and under FP7 grants n. 286403 and n. 284801 to Michele Giugliano), the European Union’s Research Area Networks (NEURON II to Stefanie Dedeurwaerdere), the Flemish Research Foundation (grants n. G0F1517N and n. K201619N to Michele Giugliano), the University of Antwerp (grant n. BOF-DOCPRO-2016 to Michele Giugliano), and the Scuola Internazionale Superiore di Studi Avanzati (“Collaborazione di Eccellenza 2018” to Michele Giugliano). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.