Abstract
We present a novel, all-electric approach to record and to precisely control the activity of tens of individual presynaptic neurons. The method allows for parallel mapping of the efficacy of multiple synapses and of the resulting dynamics of postsynaptic neurons in a cortical culture. For the measurements, we combine an extracellular high-density microelectrode array, featuring 11’000 electrodes for extracellular recording and stimulation, with intracellular patch-clamp recording. We are able to identify the contributions of individual presynaptic neurons - including inhibitory and excitatory synaptic inputs - to postsynaptic potentials, which enables us to study dendritic integration. Since the electrical stimuli can be controlled at microsecond resolution, our method enables to evoke action potentials at tens of presynaptic cells in precisely orchestrated sequences of high reliability and minimum jitter. We demonstrate the potential of this method by evoking short- and long-term synaptic plasticity through manipulation of multiple synaptic inputs to a specific neuron.
Highlights
Only few electrophysiological techniques have been introduced that allow for measuring synaptic inputs from multiple presynaptic cells
We show that high-density microelectrode arrays (HD-MEAs) recordings can be combined with the patch clamp technique, in order to precisely map and stimulate synaptic connections in networks of cultured cortical neurons
If a constant delay and low jitter was found between extracellular AP and postsynaptic potentials (PSPs), it was identified as a direct synaptic connection between the pre- and postsynaptic neuron
Summary
Only few electrophysiological techniques have been introduced that allow for measuring synaptic inputs from multiple presynaptic cells. An alternative approach includes to patch-clamp an individual neuron while, at the same time, APs of presynaptic cells are detected or actively evoked. The ‘reverse optical probing‘ technique[15, 16] applies calcium imaging and reverse correlation analysis to identify neurons that fire APs time-locked with detected synaptic events. Another approach is ‘photostimulation scanning’[17], where photolytic release of caged glutamate is applied to sequentially stimulate neurons while an individual neuron is recorded from intracellularly. We show that HD-MEA recordings can be combined with the patch clamp technique, in order to precisely map and stimulate synaptic connections in networks of cultured cortical neurons. If a constant delay and low jitter was found between extracellular AP and PSP, it was identified as a direct synaptic connection between the pre- and postsynaptic neuron
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