Investigating Neurochemistry, Connectivity, and Audio Stimuli Relationship Among Surface and Depth Cortical Neurons

Abstract In this study, we investigate the simultaneous recording of electrical and chemical signals within both the cortical surface and deep regions of the brain. This is made possible through the utilization of an innovative carbon based three-dimensional multi-functional neural probe. Our primary objectives are to explore in-depth the mechanisms of signal propagation among neuronal cells particularly within a three-dimensional framework and demonstrate initial progress in elucidating the interplay between electrical and chemical signals and their responsiveness to external stimuli variability. Approach Our innovative probe integrates epi-cortical (surface) and intra-cortical (depth) microelectrode arrays utilizing a two-dimensional thin-film microfabrication technique. This probe referred to as “epi-intra” has origami-like configuration and transforms from a two-dimensional structure into a three-dimensional configuration during implantation. Neural electrical signal recordings were conducted in the auditory region of an anesthetized European starling songbirds, whereas neurochemistry (dopamine) recordings were done simultaneously at Area X, with the animal subjected to conspecific songs as auditory stimuli. Main Results (i) This study introduces surface and depth neural recording in response to complex stimuli, such as bird songs using a three-dimensional probe with surface and depth microelectrodes. (ii) employing a transfer entropy model, a comprehensive connectivity map is established for neurons which are located on the surface of the brain, at a depth, or a combination of both, (iii) significantly, distinct spiking behavior in certain NCM (caudomedial nidopallium) neurons is observed during a specific phase of the stimulation coinciding with a peak in dopamine levels, which occurs with few milliseconds delay. This finding strongly indicates stimulus selectivity among specific neurons. Significance These findings demonstrate the creation of a connectivity map for neurons, whether located on the surface, at a depth, or a combination of both, derived from neuron recordings in response to a complex stimulus. Importantly, our study reveals that the strength of correlation and connectivity among neurons is most pronounced within surface neurons, followed by depth neurons, and comparatively weaker between surface and depth neurons. These discoveries hold significant promise in various applications, including the promise of large-scale neural electrical and electrochemical circuit mapping. Furthermore, they offer potential technology and therapeutic avenues for assisting, augmenting, or repairing human cognitive or sensory-motor functions. Competing Interest Statement The authors have declared no competing interest. Footnotes This version of the manuscript has been revised to update the corresponding author contact information and address minor formatting issues in the references and footnote sections.