Mechanisms of Cross-Modal Refinement by Visual Experience

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Mechanisms of Cross-Modal Refinement by Visual Experience

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Title: Mechanisms of Cross-Modal Refinement by Visual Experience
Author: Brady, Daniel
Citation: Brady, Daniel. 2011. Mechanisms of Cross-Modal Refinement by Visual Experience. Doctoral dissertation, Harvard University.
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Abstract: Alteration of one sensory system can have striking effects on the processing and organization of the remaining senses, a phenomenon known as cross-modal plasticity. The goal of this thesis was to understand the circuit basis of this form of plasticity. I established the mouse as a model system for studying cross-modal plasticity by comparing population activity in visual cortex between animals reared in complete darkness from birth (DR) to those housed in a normal light/dark environment (LR). I found that secondary visual cortex (V2L) responds much more strongly to auditory stimuli in DR than LR. I provide evidence that there is a sensitive period for cross-modal responses that ends in early adulthood. I also show that exposure to light later in life reduces V2L auditory activity to LR levels. I recorded single units to show that there is a higher percentage of auditory responsive neurons in DR V2L. In collaboration with Lia Min in Michela Fagiolini’s laboratory, we discovered that this was associated with an increase in the number of projections from auditory thalamus and auditory cortex. We also provide evidence that V2L is multimodal from birth and becomes less so with visual experience. I examined several molecular pathways that are affected by dark-rearing to see if they are involved in cross-modal plasticity. I found that Nogo receptor (NgR), Lynx1, and Icam5 signaling all play a fundamental role in controlling the duration of plasticity. I also show that the hyperconnectivity in NgR -/- and DR mice leads to an increase in multisensory enhancement. In primary visual cortex, cross-modal influences were much weaker. Similar to V2L, the distribution of cell types was affected by NgR signaling. I also found that both the range of cross-modal influence and its sign (excitatory or inhibitory) is dependent on visual experience. Finally, I show that NgR signaling and the maturation of inhibitory circuits affect these two properties. Together, these results provide evidence of the molecular mechanisms underlying cross-modal plasticity. We believe that this will further our knowledge of how to improve rehabilitation strategies after loss of a sensory system.
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