An experimental model of transcription-dependent synaptic plasticity

A cell culture system was developed to study synaptic plasticity. Electrical activity across cultured hippocampal networks was monitored using an array of 60 microelectrodes (MEA). These networks demonstrated spontaneous low rate asynchronous electrical activity. the GABA-A receptor antagonist bicuculline (50μM) transformed this activity into synchronous repetitive bursts of action potentials across the network, accompanied by NMDA receptor-dependent sustained global calcium transients. A 15 minute bicuculline exposure induced a long-lasting increase in synaptic efficacy, and a dramatic change in network behaviour to a highly organised, periodic and synchronous burst pattern of electrical activity across the network, which persisted for at least 24 hours. The induction of recurrent synchronous bursting had a stimulus-duration threshold. It required calcium entry through NMDA-type glutamate receptors and activation of the extracellular signal-regulated kinases ½. Maintenance of the organised state (> 4 hours) required gene transcription in a critical period of 2 hours after induction. Thus, hippocampal networks display a simple, transcription-dependent form of plasticity. Analysis of network behaviour using MEA technology provides a new experimental platform with significant advantages over the traditional assay of synaptic connectivity, long-term potentiation in hippocampal slices. Firstly, using non-invasive recording and cell cultures facilitates identification of calcium signalling pathways and activity-regulated genes critical for late-phase plasticity. Secondly, recording across a neuronal network revealed that changes in synaptic strength alter network behaviour. This simple and experimentally accessible model may give insight into the mechanisms underlying information storage and the dynamics of neuronal network properties in vivo.EThOS - Electronic Theses Online ServiceGBUnited Kingdo