Journal of Neuroscience 35: 2689-2702, 2015.
The cortical network recurrent circuitry generates spontaneous activity organized into Up (active) and Down (quiescent) states during slow wave sleep or anesthesia. These different states of cortical activation gain modulate synaptic transmission. Yet, the reported modulation that Up states impose on synaptic inputs is disparate in the literature, including both increases and decreases of responsiveness. Here we tested the hypothesis that such disparate observations may depend on the intensity of the stimuli. By means of intracellular recordings we studied synaptic transmission during Up and Down states in auditory cortex in vivo. Synaptic potentials were evoked either by auditory or electrical (thalamocortical, intracortical) stimulation, while randomly varying the intensity of the stimulus. Synaptic potentials evoked by the same stimulus intensity were compared in Up/Down states. Up states had a scaling effect on the stimulus-evoked synaptic responses: the amplitude of weaker responses was potentiated while that of larger responses was maintained or decreased with respect to the amplitude during Down states. We used a computational model to explore the potential mechanisms explaining this non-trivial stimulus-response relationship. During Up/Down states there is different excitability in the network and the neuronal conductance varies. We demonstrate that the competition between presynaptic recruitment and the changing conductance might be the central mechanism explaining the experimentally observed stimulus-response relationships. We conclude that the effect that cortical network activation has on synaptic transmission is not constant but contingent on the strength of the stimulation, with a larger modulation for stimuli involving both thalamic and cortical networks.