Hybrid neuro-electronic devices will be the basis for future information technology relying on the plasticity of networks formed by mammalian neurons in culture. Microelectronic implants interfaced with neurons in the nervous tissue will become sophisticated neuro-prostheses able to rescue impairments of the human nervous system. The present project deals with the fundamental aspect of electronic interfacing of micro structured silicon chips to rat neurons in culture. Its focus is the optimisation of electrical coupling in both directions, from excited mammalian neurons to transistors and from stimulation areas on the chip to the cells. This will be achieved with the expression of mutated sodium channels lacking inactivation in the neurons and with the induction of channels accumulation at the neuron-silicon interface. The use of highly integrated CMOS (Complementary Metal-Oxide Semiconductor) chips is envisaged. Hybrid neuro-electronic devices will be the basis for future information technology relying on the plasticity of networks formed by mammalian neurons in culture. Microelectronic implants interfaced with neurons in the nervous tissue will become sophisticated neuro-prostheses able to rescue impairments of the human nervous system. The present project deals with the fundamental aspect of electronic interfacing of micro structured silicon chips to rat neurons in culture. Its focus is the optimisation of electrical coupling in both directions, from excited mammalian neurons to transistors and from stimulation areas on the chip to the cells. This will be achieved with the expression of mutated sodium channels lacking inactivation in the neurons and with the induction of channels accumulation at the neuron-silicon interface. The use of highly integrated CMOS (Complementary Metal-Oxide Semiconductor) chips is envisaged.

OBJECTIVES
Interfacing of micro structured silicon chips to rat neurons in culture. This will be achieved with the expression of mutated sodium channels lacking inactivation in the neurons and with the induction of channels accumulation at the neuron-silicon interface.

DESCRIPTION OF WORK
In order to optimise the electrical coupling between mammalian neurons and silicon chips we will increase the ionic current flowing into the cells during recording and stimulation. At this purpose we will express in the cultured neurons voltage dependent sodium channels whose inactivation has been removed by genetic mutation. In addition we will attempt to accumulate and selectively modulate the sodium channels at the neuron-silicon interface. As a first step we will investigate the biophysics of sodium channels recording and stimulation by silicon chips using cells expressing only the mutated channels. Transfected immortalized cells, as HEK293 cells, or frog oocytes will be employed. On this basis, transfected neurons with optimal channels density and silicon chips will be interfaced. In parallel experiments we will investigate the effect of several extra cellular adhesion molecules on the localisation and modulation of mutated sodium channels. By coating the silicon with the appropriate adhesion molecules we will localise and modulate the channels at the neuron-silicon interface. We will also develop simple chips with reduced noise for improved recording of mammalian neurons and with enhanced capacitance for their stimulation. CMOS chips with thousands of transistors will be used for high-resolution multi-sites recording.