Adaptation to prolonged neuromodulation in cortical cultures: an invariable return to network synchrony

BMC Biology

Research Article

Noam E Ziv¹  Sebastian Reinartz¹  Maya Kaufman¹ 

[1] Department of Physiology and Biophysics and Rappaport Institute, Technion Faculty of Medicine, and Network Biology Research Laboratories, Lorry Lokey Center for Life Sciences & Engineering, Fishbach Building, 32000, Haifa, Israel;

关键词: Neuromodulators;    Synchrony;    Acetylcholine;    Closed-loop;    Adaptation;    Cultured neuronal networks;    Multielectrode arrays;   

DOI  :  10.1186/s12915-014-0083-3

 received in 2014-05-15, accepted in 2014-09-29,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundProlonged neuromodulatory regimes, such as those critically involved in promoting arousal and suppressing sleep-associated synchronous activity patterns, might be expected to trigger adaptation processes and, consequently, a decline in neuromodulator-driven effects. This possibility, however, has rarely been addressed.ResultsUsing networks of cultured cortical neurons, acetylcholine microinjections and a novel closed-loop `synchrony-clamp' system, we found that acetylcholine pulses strongly suppressed network synchrony. Over the course of many hours, however, synchrony invariably reemerged, even when feedback was used to compensate for declining cholinergic efficacy. Network synchrony also reemerged following its initial suppression by noradrenaline, but this did not occlude the suppression of synchrony or its gradual reemergence following subsequent cholinergic input. Importantly, cholinergic efficacy could be restored and preserved over extended time scales by periodically withdrawing cholinergic input.ConclusionsThese findings indicate that the capacity of neuromodulators to suppress network synchrony is constrained by slow-acting, reactive processes. A multiplicity of neuromodulators and ultimately neuromodulator withdrawal periods might thus be necessary to cope with an inevitable reemergence of network synchrony.

【 授权许可】

CC BY   
© Kaufman et al.; licensee BioMed Central Ltd. 2014