• context-dependent neuromodulation;
  • neuromodulators;
  • short-term synaptic plasticity;
  • sleep-wakefulness regulation;
  • synaptic transmission;
  • thalamocortical network


Thumbnail image of graphical abstract

The thalamic synapses relay peripheral sensory information to the cortex, and constitute an important part of the thalamocortical network that generates oscillatory activities responsible for different vigilance (sleep and wakefulness) states. However, the modulation of thalamic synaptic transmission by potential sleep regulators, especially by combination of regulators in physiological scenarios, is not fully characterized. We found that somnogen adenosine itself acts similar to wake-promoting serotonin, both decreasing synaptic strength as well as short-term depression, at the retinothalamic synapse. We then combined the two modulators considering the coexistence of them in the hypnagogic (sleep-onset) state. Adenosine plus serotonin results in robust synergistic inhibition of synaptic strength and dramatic transformation of short-term synaptic depression to facilitation. These synaptic effects are not achievable with a single modulator, and are consistent with a high signal-to-noise ratio but a low level of signal transmission through the thalamus appropriate for slow-wave sleep. This study for the first time demonstrates that the sleep-regulatory modulators may work differently when present in combination than present singly in terms of shaping information flow in the thalamocortical network. The major synaptic characters such as the strength and short-term plasticity can be profoundly altered by combination of modulators based on physiological considerations.

Mimicking a scenario of the sleep-onset state, we found that wake-promoting serotonin and local somnogen adenosine interact to produce robust inhibition of synaptic transmission and reverse the short-term synaptic plasticity from depression to facilitation in the sensory thalamus, effects not achievable by one modulator alone but consistent with the expected electrophysiological characteristics at sleep. Thus, the relay of information through the thalamus can be finely tuned in a vigilance state-dependent context-specific manner by neuromodulators from both distant and local sources.