Amplified Auditory Response Following Activation of the Projection from Anterior Cingulate Cortex Leads to Increased Flight Behavior of the Mouse

前扣帶皮層的投射通過放大聽覺反應從而增強小鼠的逃跑行為

Student thesis: Doctoral Thesis

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Award date14 Jan 2021

Abstract

Top-down modulation of sensory processing allows animals to respond appropriately to environmental stimuli. Here, we discovered a role of anterior cingulate cortex (ACC) to auditory cortex (AC) projection in air puff facilitated noise-induced flight responses.

First, we found that the AC extensively involved in air puff facilitated noise-induced flight responses. When an air puff was delivered prior to a noise, it facilitated noise-induced flight responses in mice, by increasing the flight speed and decreasing the noise threshold. Moreover, AC inactivation by local muscimol injection eliminated noise-induced flight responses even with an air puff. Using fiber photometry-based calcium recording, we found that calcium responses to noise were enhanced by delivery of an air puff before the noise.

Second, to gain a deeper understanding of where this enhancement of auditory responses originated from, retrograde tracing was carried out. It was found that the ACC had the strongest retrogradely labeled neuron density in the prefrontal area. The ACC to AC projection was further verified by anterograde tracing, and both superficial and deep layers of the AC were found to receive strong projections from the anterior ACC, but not the posterior ACC. Fiber photometry recordings revealed that ACC to AC projecting neurons were activated by the air puff. To clarify whether the ACC participates in air puff facilitated noise-induced flight responses, the ACC was silenced during behavioral tasks by local muscimol injection, and it was found that ACC silencing could abolish the facilitation effect of the air puff. Moreover, extracellular recording results showed that the ACC could facilitate AC auditory responses in both deep and superficial layers through its excitatory projections in anesthetized mice, which provided physiological evidence for the facilitation effect of the air puff during noise-induced flight behavior.

Lastly, to investigate whether the manipulation of this projection would affect noise-induced flight behavior, optogenetic activation was used. We found that noise-induced flight responses could be enhanced by the activation of ACC terminals in the AC, which mimickeds the facilitation effect of the air puff. Moreover, chemogenetic silencing of the projecting terminals was carried out to determine the inhibitory effect of this ACC to AC projection. It was found that the facilitation effect of the air puff could be eliminated by chemogenetic silencing of ACC terminals in the AC. Thus, our results regarding this modulation of the AC by the ACC can help deepen our understanding of the top-down modulation of auditory processing and provide potential clinical treatment targets for disordered auditory processing.

    Research areas

  • Anterior cingulate cortex, Auditory cortex, Top-down modulation, Noise-induced flight response, Alertness, Air puff, Chemogenetics, Optogenetics