Plasticity of neuronal response properties in mouse visual cortex assessed with two-photon calcium imaging

Neurons in the mammalian primary visual cortex (V1) respond to contours in the visual field, and, for most cells, response strength depends on contour orientation. This property, orientation selectivity, can develop without any visual input. However, orientation selectivity is plastic, and it can be modified by visual experience. In this thesis, I have investigated two types of functional plasticity, namely experience-dependent and learning-induced plasticity. Experience-dependent plasticity of orientation preference can be induced by stripe rearing. In this paradigm, an animal is exposed to contours of only a single orientation, causing an over-representation of the experienced orientation in the visual cortex. Two competing hypotheses have been put forward to explain this effect: The permissive hypothesis proposes that neurons, which are not tuned to the experienced orientation, lose responsiveness, leaving only neurons, which are driven by the experienced orientation. In contrast, the instructive hypothesis suggests that neurons actively change their preferred orientation towards the experienced one. Accordingly, the permissive hypothesis predicts a drop in the number of responsive neurons, which would not to be expected, if the instructive hypothesis was true. In order to solve this issue, I took advantage of two-photon calcium imaging, a method which allows reliably determining the fraction of responsive neurons. Mice were stripe reared for three weeks with goggles containing cylinder lenses. Subsequent two-photon calcium imaging using the synthetic calcium sensor OGB1-AM revealed a dominant role of instructive mechanisms during stripe rearing in layer 2/3 of mouse V1. More specifically, the stripe rearing effect was depth-dependent: In lower layer 2/3, the absolute number of neurons preferring the experienced orientation increased, indicating an instructive change. In upper layer 2/3, the fraction of responsive neurons dropped slightly, but this drop was not correlated with the Summary 12 magnitude of the stripe rearing effect in individual mice. Thus, permissive effects cannot be completely excluded, but the slight decrease in responsiveness is unlikely to cause the overall stripe rearing effect. Rather, instructive effects, for example a change in the preferred orientation of individual neurons, underlie the stripe rearing effect in mouse visual cortex. Learning-induced plasticity in the visual system can be elicited by a modified assignment of behavioral relevance to a visual stimulus. However, whether early sensory areas such as V1 are involved in learning is highly controversial. Hierarchical models of the visual system assign a mainly infrastructural role to V1, merely distributing incoming visual signals to higher cortical areas. Interactive …