We report the realization of electrical coupling between neurons and depletion type floating gate (FG) p-channel MOS transistors. The devices were realized in a shortened 0.5 mum CMOS technology. Increased boron implant dose was used to form the depletion type devices. Post-CMOS processing steps were added to expose the devices sensing area. The neurons are coupled to the polycrystalline silicon (PS) FG through 420 A thermal oxide in an area which is located over the thick field oxide away from the transistor. The combination of coupling area pad having a diameter of 10 or 15 mum and sensing transistor with W/L of 50/0.5 mum results in capacitive coupling ratio of the neuron signal of about 0.5 together with relatively large transistor transconductance. The combination of the FG structure with a depletion type device, leads to the following advantages. (a) No need for dc bias between the solution in which the neurons are cultured and the transistor with expected consequences to the neuron as well as the silicon die durability. (b) The sensing area of the neuron activity is separated from the active area of the transistor. Thus, it is possible to design the sensing area and the channel area separately. (c) The channel area, which is the most sensitive part of the transistor, can be insulated and shielded from the ionic solution in which the neurons are cultured. (d) There is an option to add a switching transistor to the FG and use the FG also for the neuron stimulation. (C) 2004 Elsevier B.V. All rights reserved.