The project concerns the design, development and optimization of an in vitro system to replace the use of animals in experiments in transgenics and toxicology, on studies related with effects of genes, (transgenics) or chemicals, (toxicology), on neural tissue structure and function and in particular on studies related with memory and learning.

The in vitro system consists of a three-dimensional neural tissue-like construct. It is formed by the synaptic connections developed among neurons that are generated from mouse embryonic stem cells. The neurons are inside a porous biomaterial which contains molecules that guide the development of the synaptic network. The tissue is interfaced at two opposite sides with multielectrode arrays for electrical stimulation and response recording. During the development of the synaptic connections, an electrical stimulation is applied so that the final synaptic connectivity pattern will be stimulus-specific and will generate a stimulus-specific electrical response.

Based on the signal features of the response, it could be evaluated when the tissue has “memorized” the electrical signal. The objective is to use in vitro developed neural tissues instead of transgenic animals having emory and learning deficiencies. For this reason the tissue will be developed in vitro from mbryonic cell lines that have genes involved in memory/learning switched-off, (transgenic issue). The ability of the transgenic tissue to memorize electrical stimuli will be checked and ompared with this of the normal tissue. In this way, the role of genes in memory/learning can be checked in vitro providing preliminary information at the tissue level to orient the design of the transgenic animals towards the optimal ones that have high probability to have altered phenotype, decreasing in this way the number of transgenic animals that are currently generated by trial-and-error methods.