Multiscale Investigations of Cortical Processing by Integrating Laminar Polytrodes and Optogenetics with Micro...

Electrocorticography (ECoG) is a methodological bridge between basic neuroscience and understanding human brain function in health and disease. ECoG records neurophysiological signals directly from the cortical surface at millisecond temporal resolution and columnar spatial resolution over large regions of cortical tissue simultaneously, making it uniquely positioned to study both local and distributed cortical computations. Here, we describe the design of custom, high-density micro-ECoG (µECoG) devices and their use in two procedures. These grids have 128 low-impedance electrodes with 200 µm spacing fabricated on a clear polymer substrate with perforations between electrodes; these features enable simultaneous µECoG recording with laminar polytrode recordings and optogenetic manipulations. First, we present a protocol for combined epidural µECoG recording over the whisker somatosensory cortex of mice with optogenetic manipulation of specific genetically defined cortical cell types. This allows causal dissection of the distinct contributions of different neuronal populations to sensory processing while also monitoring their specific signatures in µECoG signals. Second, we present a protocol for acute experiments to record neural activity from the rat auditory cortex using µECoG grids and laminar polytrodes. This allows detailed topographic mapping of sensory-evoked neural responses across the cortical surface simultaneously with recordings from multiple neural units distributed across the cortical depth. These protocols enable experiments that characterize distributed cortical activity and may contribute to understanding and eventual interventions for diverse neurological disorders.