Local versus global effects of isoflurane anesthesia on visual processing in the fly brain

Abstract

What characteristics of neural activity distinguish the awake and anesthetized brain? Drugs such as isoflurane abolish behavioral responsiveness in all animals, implying evolutionarily conserved mechanisms. However, it is unclear whether this conservation is reflected at the level of neural activity. Studies in humans have shown that anesthesia is characterized by spatially distinct spectral and coherence signatures that have also been implicated in the global impairment of cortical communication. We questioned whether anesthesia has similar effects on global and local neural processing in one of the smallest brains, that of the fruit fly (Drosophila melanogaster). Using a recently developed multi-electrode technique, we recorded Local Field Potentials (LFPs) from different areas of the fly brain simultaneously, while manipulating the concentration of isoflurane. Flickering visual stimuli (‘frequency tags’) allowed us to track evoked responses in the frequency domain and measure the effects of isoflurane throughout the brain. We found that isoflurane reduced power and coherence at the tagging frequency (13 or 17Hz) in central brain regions. Unexpectedly, isoflurane increased power and coherence at twice-the tag frequency (26 or 34Hz) in the fly’s optic lobes, but only for specific stimulus configurations. By modeling the periodic responses, we show that the increase in power in peripheral areas can be attributed to local neuroanatomy. We further show that the effects on coherence can be explained by impacted Signal to Noise Ratios (SNR). Together, our results show that general anesthesia has distinct local and global effects on neuronal processing in the fruit fly brain.

Significance Statement Understanding the neural basis of general anesthesia is important for both clinical and consciousness research. Studies in humans show that general anesthesia has distinct local and global effects. Here, we show homologous findings in the fruit fly brains, taking us a step closer to understanding how loss of consciousness under general anesthesia is evolutionarily conserved across different neuroanatomies. Our unique combination of methods demonstrates that 1) frequency tagging can be used to dissect the neural mechanisms of general anesthesia, 2) anesthesia manipulations deepen our mechanistic understanding of neural processing, and 3) simple modeling can help clarify unexpected results.