Heterogeneous synaptic homeostasis: A novel mechanism boosting information propagation in the cortex

Perceptual awareness of auditory stimuli decreases from wakefulness to sleep, largely due to reduced cortical responsiveness. During wakefulness, neural responses to external stimuli in most cortical areas exhibit a broader spatiotemporal propagation pattern compared to deep sleep. A potential mechanism for this phenomenon is the synaptic upscaling of cortical excitatory connections during wakefulness, as posited by the synaptic homeostasis hypothesis. However, we argue that uniform synaptic upscaling alone cannot fully account for this observation. We propose a novel mechanism suggesting that the upscaling of excitatory connections between different cortical areas exceeds that within individual cortical areas during wakefulness. Our computational results demonstrate that the former promotes the transfer of neural responses and information, whereas the latter has diminishing effects. These findings highlight the necessity of heterogeneous synaptic upscaling and suggest the presence of heterogeneity in receptor expression for neuromodulators involved in synaptic modulation along the dendrite.Author summary: As we transition from wakefulness to sleep, our perception of the external world fades, and the brain’s neural activity undergoes profound changes. Neurons not only alter their firing patterns, but the strength of their synaptic connections also weakens during sleep and increases upon waking. While this process, known as synaptic homeostasis, is gaining experimental validation, its causal link to the accompanying changes in brain activity and cognition are not fully elucidated. A hallmark of wakefulness is the ability of external stimuli to propagate across widespread cortical areas, engaging multiple sensory regions–something that is limited during sleep. Here, we use a computational model to show that uniformly increasing synaptic strength across different spatial scales does not replicate this enhanced signal propagation. Instead, we find that selectively strengthening long-range excitatory connections–those linking distant regions–boosts signal spread more effectively than uniform changes, which primarily increase spontaneous activity and disrupts signal transmission. These findings refine the synaptic homeostasis hypothesis and highlight the role of spatial rules in shaping network connectivity to effectively modulate information processing across the sleep wake cycle.