Synaptic dynamics contribute to long-term single neuron response fluctuations

Firing rate variability at the single neuron level is characterized by long-memory processes and complex statistics over a wide range of time scales (from milliseconds up to several hours). Here, we focus on the contribution of non-stationary efficacy of the ensemble of synapses-activated in response to a given stimulus-on single neuron response variability. We present and validate a method tailored for controlled and specific long-term activation of a single cortical neuron in vitro via synaptic or antidromic stimulation, enabling a clear separation between two determinants of neuronal response variability: membrane excitability dynamics vs. synaptic dynamics. Applying this method we show that, within the range of physiological activation frequencies, the synaptic ensemble of a given neuron is a key contributor to the neuronal response variability, long-memory processes and complex statistics observed over extended time scales. Synaptic transmission dynamics impact on response variability in stimulation rates that are substantially lower compared to stimulation rates that drive excitability resources to fluctuate. Implications to network embedded neurons are discussed. \ua9 2014 Reinartz, Biro, Gal, Giugliano and Marom

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

This work was supported by the European Union\u2019s 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\u2019s 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 (\u2018\u2018Collaborazione di Eccellenza 2018\u2019\u2019 to Michele Giugliano). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Brief wide-field photostimuli evoke and modulate oscillatory reverberating activity in cortical networks

Cell assemblies manipulation by optogenetics is pivotal to advance neuroscience and neuroengineering. In in vivo applications, photostimulation often broadly addresses a population of cells simultaneously, leading to feed-forward and to reverberating responses in recurrent microcircuits. The former arise from direct activation of targets downstream, and are straightforward to interpret. The latter are consequence of feedback connectivity and may reflect a variety of time-scales and complex dynamical properties. We investigated wide-field photostimulation in cortical networks in vitro, employing substrate-integrated microelectrode arrays and long-term cultured neuronal networks. We characterized the effect of brief light pulses, while restricting the expression of channelrhodopsin to principal neurons. We evoked robust reverberating responses, oscillating in the physiological gamma frequency range, and found that such a frequency could be reliably manipulated varying the light pulse duration, not its intensity. By pharmacology, mathematical modelling, and intracellular recordings, we conclude that gamma oscillations likely emerge as in vivo from the excitatory-inhibitory interplay and that, unexpectedly, the light stimuli transiently facilitate excitatory synaptic transmission. Of relevance for in vitro models of (dys)functional cortical microcircuitry and in vivo manipulations of cell assemblies, we give for the first time evidence of network-level consequences of the alteration of synaptic physiology by optogenetics