A fundamental property of neurons in the primary visual cortex is their preference for orientation of edges. It was shown that this orientation tuning is mostly invariant under contrast changes [1], a property that is not explained by a simple feed-forward scheme [2, 3]. We designed a synthetic hybrid neural circuit to study the emergence of orientation selectivity under different thalamo-cortical connections. To this end, a computational model of the retino-thalamic pathway was combined with an in-vitro model of cortical input layer 4. The latter was either a primary culture of cortical neurons or an acute brain slice of primary visual cortex. The two stages were interfaced optogenetically by expression of channelrhodopsin in the neurons of the in-vitro circuit and holographic stimulation. Neural activity was then monitored either electrophysiologically with multielectrode arrays or by fluorescent imaging. In our model we implemented a connection scheme with thalamocortical input that is retinotopic but unselective for orientation. Interestingly, we measured orientation selective responses in the cortical activity that we reasoned had to be generated intrinsically by the target network. Next, we tested the effect of different contrast levels and found that the orientation selectivity can change for individual neurons but is stable on the population level. In summary, we showed that contrast-invariant orientation preference can emerge from unspecific thalamo-cortical input in two different target networks.