| Popis: |
In the visual system, prolonged exposure to a high contrast stimulus leads to a decrease in neuronal responsiveness, referred to as contrast adaptation. Contrast adaptation has been extensively studied in carnivores and primates, but has so far received little attention in mice. This thesis explores contrast adaptation and its mechanisms in mouse primary visual cortex (V1). Using extracellular tetrode recordings in mouse V1, I found contrast adaptation to be orientation unspecific. While this finding differs from reports in carnivores and primates, it is consistent with the notion that responsiveness of individual neurons is influenced by the activity history of the local network. Adaptation was also found to be cell-type specific, as putative parvalbumin (PV) expressing interneurons underwent less adaptation than other cell types. There is debate whether adaptation arises within the cortex or is inherited from the earlier stages in the visual pathway (e.g. visual thalamus or retina). In order to assess the relative contributions of cortical/subcortical mechanisms towards adaptation in mouse V1, I used optogenetic methods to suppress cortical activity (via activation of Channelrhodopsin-2 in PV interneurons) during an adapting stimulus. Suppressing cortical activity, and hence any activity-dependent cortical mechanisms, largely counteracted the effects of adaptation on neuronal responsiveness, consistent with a substantial cortical component of adaptation. Interestingly, whilst adaptation reduced both contrast and response gain, only the latter effect was influenced by cortical suppression. This suggests that the mechanisms mediating adaptation-induced alterations in contrast and response gain are different, and possibly occur at different loci within the visual pathway. The consequences of adaptation on V1 population responses were explored with two-photon calcium imaging. Adaptation to dynamic stimuli of multiple orientations caused a divisive scaling of responses, consistent with a reduction in response gain. Adaptation also decorrelated neuronal activity, leading to sparser and more distributed stimulus representations across the population. Whole-cell recordings further revealed that these effects were associated with decreased membrane depolarisation, and an increase in membrane potential variability. |
