Extracellular electrical stimulation and recording of neural activity is an important tool in investigating the function of the nervous system. Traditionally, electrical stimulation has been achieved through bipolar electrodes or passive multi electrode arrays (MEAs) with small number of channels and/or with coarse spatial resolution. The ability to elicit activities with high spatial and temporal resolution, and over a large neuronal population, will provide an important new tool for understanding structure and function of the central nervous system.
We construct an active array-based system to provide high-density, high-resolution stimulation patterns to neural cultures and acute brain slices. We explore the limits of extracellular stimulation of neural activity with an electrode array capacitively coupled to the tissue in a non-Faradaic interface. The die photo shows one of our multielectrode array chips. With a 256 by 256 electrode array, it can provide a stimulation pulse train on each electrode with unique pulse duration, number of pulses, and separation interval between the pulses. The 4x4 mm2 die was fabricated in 2.5V 0.25 um CMOS technology with a density of 6,724 electrodes per mm2 at a pitch of 12 um. A 20 nm thick hafnium oxide (HfO2) film is deposited onto planarized aluminum electrodes by atomic layer deposition, blocking Faradaic processes at the interface.
The experiments performed combine electrical stimulation from the chip with optical recording, utilizing Ca2+ sensitive dyes to observe intracellular calcium concentration change as an indirect measure of action potential.
We have demonstrated successful stimulation of action potential in thalamocortical acute slices from the active substrate. A stimulation pulse train applied to all electrodes induces widespread activation of neurons in the tissue. Stimulation was also applied to the acute slice at a point remote from the recorded activity by selectively activating left half of the array. Action potential progression from the point of stimulation as a ‘wave’ of activity in large population of neurons was also observed.
These results are guiding interdisciplinary studies with acute brain slices and dispersed neuronal cultures, and the development of new MEAs capable of both extracellular stimulation and recording.
- N. Lei, B. Watson, J. MacLean, R.Yuste, and K. Shepard, "A 256-by-256 CMOS microelectrode array for extracellular stimulation of acute brain slices", Digest of Technical Papers, International Solid-State Circuits Conference, 2008
- N. Lei and S. Ramakrishnan and P. Shi and J. S. Orcutt and R. Yuste and L. C. Kam and K. L. Shepard, “High-resolution extracellular stimulation of dispersed hippocampal culture with high-density CMOS multielectrode array based on non-Faradaic electrodes”, J Neural Eng. (2011), vol. 8, pp 044003.
- D Tsai, E John, T Chari, R Yuste, K L Shepard, "High–channel–count, high–density micro- electrode array for closed–loop investigation of neuronal networks," Proceedings of the 37th Annual International Conference of the IEEE EMBS, 2015