Investigation and modulation of neural circuits in vivo at the cellular level are very important for studying functional connectivity in a brain. Recently, neural probes with stimulation capabilities have been introduced, and they provided an opportunity for studying neural activities at a specific region in the brain using various stimuli. However, previous methods have a limitation in dissecting long-range neural circuits due to inherent limitations on their designs. Moreover, the large size of the previously reported probes induces more significant tissue damage. Herein, we present a multifunctional multi-shank MEMS neural probe that is monolithically integrated with an optical waveguide for optical stimulation, microfluidic channels for drug delivery, and microelectrode arrays for recording neural signals from different regions at the cellular level. In this work, we successfully demonstrated the functionality of our probe by confirming and modulating the functional connectivity between the hippocampal CA3 and CA1 regions in vivo.

Multi-functional neural probes integrated with various stimulation modalities are becoming essential tools in neuroscience to study the brain more effectively. In this paper, we present a new multi-functional neural probe that allows chemical stimulation through drug delivery and simultaneous recording of individual neuron signals through a microelectrode array. By embedding microchannels in silicon using a proposed glass reflow process, we successfully fabricated 40 μm thick silicon neural probes suitable for small animal experiments. The electrochemical impedance spectroscopy confirms that impedance of iridium microelectrodes is low enough (<1 MΩ at 1 kHz) to measure neural signals. Flow rate characterization in a 0.9% w/v agarose gel shows the capability to deliver a small volume of drugs (<1 μl) at a controlled flow rate. We demonstrate the viability and potential of this new probe by conducting in vivo experiments on mice. Because of the proposed compact structure, both action potentials of individual neurons and local field potentials (LFP) at the thalamus region of a mouse brain were successfully detected with a noise level of ~30 μVpp. Furthermore, we successfully induced absence seizure by injecting seizure-inducing drugs (baclofen) at a local target region and observed distinctive changes in neural signal patterns. Specifically, spike-wave discharge (SWD), which is an indicative signal pattern of absence seizure, was successfully recorded. These signals were also directly compared to SWD detected after inducing absence seizure through direct injection of baclofen through the abdomen. This work demonstrates the potential of our multi-functional neural probes for use in effective investigation of brain functions and disorders by using widely available mouse models.