Chronic network stimulation enhances evoked action potentials

Abstract

Neurons cultured on multielectrode arrays almost always lack external stimulation except during the acute experimental phase. We have investigated the effects of chronic stimulation during the course of development in cultured hippocampal neural networks by applying paired pulses at half of the electrodes for 0, 1, or 3 hr/day for 8 days. Spike latencies increased from 4 to 16 ms as the distance from the stimulus increased 200–1700 μm, suggesting an average of 4 synapses over this distance. Compared to no chronic stimulation, our results indicate that, chronic stimulation increased evoked spike counts per stimulus by 50% at recording sites near the stimulating electrode and increased the instantaneous firing rate. On trials where both pulses elicited responses, spike count was 40–80% higher than when only one of the pulses elicited a response. In attempts to identify spike amplitude plasticity, we found mainly amplitude variation with different latencies suggesting recordings from neurons with different identities. These data suggest plastic network changes induced by chronic stimulation that enhance the reliability of information transmission and the efficiency of multisynaptic network communication.

Hippocampal networks on reliable patterned substrates

“…Because random networks under our conditions display an average synaptic delay time of 4–5 ms and total time for a stimulus to cross the network of 20 ms (Ide et al, 2010), we computed the cross-correlations of spontaneous spikes between electrodes within these narrow limits for the patterned networks and divided by the number of active electrodes for each array. Fig.…”

“…Stimulation trains consisted of two pairs of 30 µA pulses (biphasic, 100 µs/phase, positive first) with a 50 ms interval between each pulse in the pair and a 5 s interval between pairs (Ide et al, 2010). An automatic stimulation program was created using Microsoft Visual C++ 2008 that applied the stimulation train to all 59 electrodes on the MEA in a sequence consisting of two phases: 1) single electrodes were stimulated in a pseudorandom sequence such that consecutive electrodes were not adjacent to each other, and 2) diagonally adjacent pairs of electrodes were simultaneously stimulated in a pseudorandom sequence such that consecutive pairs of electrodes were not adjacent to each other.…”

“…Background noise levels were computed as the minimum standard deviation of 1-second windows over the entire recording. Spikes were detected as peak-to-peak deviations of 11× the noise (Ide et al, 2010) in 2 ms sliding windows with a post spike dead time of 1 ms (Maccione et al, 2009). To automatically reject shorted or open electrodes, active channels were selected with a minimum background noise of 1 µV and a maximum of 10 µV, respectively.…”

“…In random, non-patterned cultures, these ingredients increase synapse density 2-fold and result in 4-fold higher spike rates. Second, cultures were stimulated daily during development as we had shown previously that chronic stimulation improved activity (Brewer et al, 2009; Ide et al, 2010). Stimulation of 1–3 hr/day for 2 weeks increases spontaneous spike rates 2-fold after 3 weeks in culture and recruits up to 50% more active electrodes as well as doubling the spike frequency within bursts.…”

Experimental model of neuronal network learning in dissociated hippocampal cultures

“…Показано, что низкочастотная стимуляция не вызывает ни кратковременных ни долгосрочных изменений функциональной структуры нейронной сети и ответа на стимул [15]. Тем не менее, в ряде исследований установлено изменение структуры в спонтанно генерируемой пачечной активности и функциональной связанности под действием низкочастотной стимуляции [3,16,17,18].…”