Piezo2, A Pressure Sensitive Channel Is Expressed in Select Neurons of the Mouse Brain: a Putative Mechanism for Synchronizing Neural Networks by Transducing Intracranial Pressure Pulses

Abstract

Abstract Piezo2 expression in mouse brain was examined using an anti-PIEZO2 antibody (Ab) generated against a C-terminal fragment of the human PIEZO2 protein. As a positive control for Ab staining of mouse neurons, the Ab stained a majority of mouse dorsal root ganglion (DRG) neurons, consistent with recent in situ hybridization and single cell RNA sequencing studies of Piezo2 expression. As a negative control and test for specificity, the Ab failed to stain human erythrocytes, which selectively express PIEZO1. In brain slices isolated from the same mice as the DRG, the Ab displayed high selectivity in staining specific neuron types, including pyramidal neurons in the neocortex and hippocampus, Purkinje cells in the cerebellar cortex and mitral cells in the olfactory bulb. Given the demonstrated role of Piezo2 channels in peripheral neurons as a low-threshold pressure sensor (i.e., ≤ 5 mm Hg) critical for the regulation of breathing and blood pressure, its expression in select brain neurons has interesting implications. In particular, we hypothesize that Piezo2 provides select brain neurons with an intrinsic resonance enabling their entrainment by the normal intracranial pressure (ICP) pulses (~ 5 mm Hg) associated with breathing and cardiac cycles. This mechanism could serve to increase the robustness of respiration-entrained oscillations previously reported across widely distributed neuronal networks in both rodent and human brains. This idea of a “global brain rhythm” has previously been thought to arise from the effect of nasal airflow activating mechanosensitive neurons within the olfactory epithelium, which then synaptically entrain mitral cells within the olfactory bulb and through their projections, neural networks in other brain regions, including the hippocampus and neocortex. Our proposed, non-synaptic, intrinsic mechanism in which Piezo2 tracks the “metronome-like” ICP pulses would have the advantage that spatially separated brain networks could also be synchronized by a physical force that is rapidly transmitted throughout the brain.