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.

Phosphorylation Hypothesis of Sleep

“…The synchronous slow oscillation appears to be the inherent property of cortical neuron assemblies because the oscillation can be found in ex vivo cortical slabs/slices ( Sanchez-Vives and McCormick, 2000 ; Timofeev et al, 2000 ). It was even shown that the cultured neurons exhibit a synchronous firing pattern similar to that of slow oscillation, and the synchronous firing pattern can be converted to asynchronous one by applying chemical(s) including excitatory neurotransmitters ( Hinard et al, 2012 ; Kaufman et al, 2014 ; Saberi-Moghadam et al, 2018 ). Overall, the synchronous slow oscillation of cortical neurons can be modulated through multiple layers of neurotransmitters, brain circuits, and neuronal networks.…”

Activity changes in neuron-astrocyte networks in culture under the effect of norepinephrine

“…Recent investigations suggest that global processes, in particular neuromodulation, play important roles in brain network dynamics [ 13 , 14 ] by affecting neuron-astrocyte network communication [ 15 ]. Triggered by global changes (e.g., behavior or body temperature), neuromodulation regulates and stimulates brain activity by volume transmission, a process by which chemicals spread from the site of secretion through the brain extracellular fluid to affect a large number of cells [ 16 , 17 ].…”

Mechanisms of Self-Sustained Oscillatory States in Hierarchical Modular Networks with Mixtures of Electrophysiological Cell Types

“…Electrophysiological studies have shown that SSA states in the above situations share the same basic features (Sanchez-Vives and McCormick, 2000 ; Mao et al, 2001 ; Steriade et al, 2001 ; Cossart et al, 2003 ; Shu et al, 2003 ; Kaufman et al, 2014 ). As revealed by EEG or local field potential measurements, they are characterized by slow (< 1 Hz) network oscillations, consisting of epochs of high network activity intercalated with periods of nearly absent network activity.…”