A fundamental property of neurons in the primary visual cortex is their preference for orientation of edges that is invariant under contrast changes. We designed a synthetic hybrid neural circuit to study the emergence of orientation selectivity under different thalamo-cortical connection schemes. 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 horizontal 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 monitored either electrophysiologically with multielectrode arrays or by calcium imaging.In this model we implemented a connection scheme with thalamo-cortical input that is retinotopic but unselective for orientation. Interestingly, we measured orientation selective responses in the cortical activity that is generated intrinsically by the target network. Next, we tested the effect of different contrast levels and found that orientation selectivity can slightly change for individual neurons but is stable on the population level. In summary, we demonstrate that contrast-invariant orientation tuning can emerge from unspecific thalamo-cortical input.