title: Adaptation to prolonged neuromodulation in cortical cultures: an invariable return to network synchrony.
abstract: BACKGROUND
  Prolonged 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.
  
  
  RESULTS
  Using 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.
  
  
  CONCLUSIONS
  These 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.
authors.forename: Maya
authors.initials: M
authors.lastname: Kaufman
authors.forename: Sebastian
authors.initials: S
authors.lastname: Reinartz
authors.forename: Noam E
authors.initials: NE
authors.lastname: Ziv
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D055724:Electrophysiological Phenomena; D023421:Models, Animal; D008962:Models, Theoretical; D009474:Neurons / Q000166:cytology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003470:Culture Media; D018377:Neurotransmitter Agents