Spatio-temporal patterns of population responses in the visual cortex under Isoflurane: from wakefulness to loss of consciousness

Abstract

Anesthetic drugs are widely used in medicine and research to mediate loss of consciousness (LOC). Despite the vast use of anesthesia, how LOC affects cortical sensory processing and the underlying neural circuitry, is not well understood. We measured neuronal population activity in the visual cortices of awake and isoflurane anesthetized mice and compared the visually evoked responses under different levels of consciousness. We used voltage-sensitive dye imaging (VSDI) to characterize the temporal and spatial properties of cortical responses to visual stimuli over a range of states from wakefulness to deep anesthesia. VSDI enabled measuring the neuronal population responses at high spatial (meso-scale) and temporal resolution from several visual regions (V1, extrastiate-lateral (ESL) and extrastiate-medial (ESM)) simultaneously. We found that isoflurane has multiple effects on the population evoked response that augmented with anesthetic depth, where the largest changes occurred at LOC. Isoflurane reduced the response amplitude and prolonged the latency of response in all areas. In addition, the intra-areal spatial spread of the visually evoked activity decreased. During visual stimulation, intra-areal and inter-areal correlation between neuronal populations decreased with increasing doses of isoflurane. Finally, while in V1 the majority of changes occurred at higher doses of isoflurane, higher visual areas showed marked changes at lower doses of isoflurane. In conclusion, our results demonstrate a reverse hierarchy shutdown of the visual cortices regions: low-dose isoflurane diminishes the visually evoked activity in higher visual areas before lower order areas and cause a reduction in inter-areal connectivity leading to a disconnected network.