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The effects of brain state and behavioral relevance on sensory representations in awake mouse auditory cortex

  • Author(s): Lin, Pei-Ann
  • Advisor(s): Isaacson, Jeffry S
  • et al.
Abstract

Sensory representations in the brain are constantly modulated by a variety of factors such as brain state and behavioral context. This dissertation seeks to build a deeper understanding of how our brains accurately represent the world around us by utilizing two-photon calcium imaging of awake mouse auditory cortex during passive listening and learning. I begin with an overview of the anatomical organization of primary auditory cortex (A1) projection neurons. By using spectrally-distinct retrograde tracers, I labeled projection populations from A1 to three functionally distinct brain regions: caudate putamen, inferior colliculus, and contralateral A1. By visualizing the distribution of and overlap between each tracer, I found that the spatial organization of these projection populations were markedly distinct, and labeled neurons rarely projected to more than one target region. These results suggest that A1 projections are organized in a manner that is conducive to target-relevant information transfer. Next, I functionally characterized projections from the lateral amygdala (LA), a structure implicated in emotion processing, to secondary auditory cortex (A2). I observed that discriminative auditory fear conditioning (DAFC) bidirectionally modulates the strength of A2 amygdalar axon responses to the aversive (CS+) and neutral (CS-) tones. Additionally DAFC-related plasticity was not sufficient for immediately driving expression of discriminative fear behavior, suggesting that LA serves as a primary site of discriminative fear memory. Follow-up experiments characterizing the effects of DAFC on local A2 neurons are necessary in order to fully appreciate the significance of these preliminary findings. Finally, I investigated whether arousal state modulates A1 sensory representations. Pyramidal cell response strength and reliability increased with arousal, resulting in broader frequency tuning and stronger signal correlations. Although this increase in tuning overlap, in isolation, would be detrimental to frequency discrimination, nonlinear classifier decoding accuracy improves with arousal. To reconcile this discrepancy, I delved deeper into the effects of arousal on population activity and found that noise correlations decrease for cells that show stronger signal correlations and increase for cells that show weaker signal correlations as arousal increases. This divergence in correlations has been shown both theoretically and experimentally to improve stimulus discrimination. Taken together, arousal strengthens A1 layer 2/3 tone-evoked responses and modulates inter-neuronal correlations in a nuanced manner that ultimately improves frequency discrimination.

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