Developed biological systems are endowed with the ability of interacting with the environment; they sense the external state and react to it by changing their own internal state. Many attempts have been made to build 'hybrids' with the ability of perceiving, modifying and reacting to external modifications. Investigation of the rules that govern network changes in a hybrid system may lead to finding effective methods for 'programming' the neural tissue toward a desired task. Here we show a new perspective in the use of cortical neuronal cultures from embryonic mouse as a working platform to study targeted synaptic modifications. Differently from the common timing-based methods applied in bio-hybrids robotics, here we evaluated the importance of endogenous spike timing in the information processing. We characterized the influence of a spike-patterned stimulus in determining changes in neuronal synchronization (connectivity strength and precision) of the evoked spiking and bursting activity in the network. We show that tailoring the stimulation pattern upon a neuronal spike timing induces the network to respond stronger and more precisely to the stimulation. Interestingly, the induced modifications are conveyed more consistently in the burst timing. This increase in strength and precision may be a key in the interaction of the network with the external world and may be used to induce directional changes in bio-hybrid systems.