Abstract
Here we use immunohistochemistry to examine the expression of Piezo2 in neurons of the mouse dorsal root ganglia and brain. Whereas Piezo2 is expressed in the large majority (≥ 90%) of dorsal root ganglia neurons, Piezo2 expression is restricted to select neuron types in specific brain regions, including neocortical and hippocampal pyramidal neurons, cerebellar Purkinje cells and mitral cells of the olfactory bulb. Given the well-established role of Piezo2 as a low-threshold pressure sensor (i.e., ≤5 mmHg) in peripheral mechanosensation, including the regulation of breathing and blood pressure, its expression in central neurons has interesting implications. In particular, we hypothesize that Piezo2 provides neurons with an intrinsic resonance that promotes their entrainment by the normal intracranial pressure pulses (~5 mmHg) associated with breathing and cardiac cycles. The pressure-induced change in neural activity need only be very subtle to increase, for example, the robustness of respiration-entrained oscillations reported previously in widely distributed neuronal networks in both rodent and human brains. This idea of a "global brain rhythm" first arose from the effect of nasal airflow in activating mechanosensitive olfactory sensory neurons, 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, where Piezo2 tracks the highly predictable and "metronome-like" intracranial pressure pulses-to date generally considered epiphenomena-would have the advantage that a physical force rapidly transmitted throughout the brain also contributes to this synchronization.
Highlights
Piezo2 is a pressure-activated channel expressed in peripheral neurons and known to play key roles in peripheral mechanosensation [2,3,4] including the regulation of arterial blood pressure [5] and breathing [6]
We were interested in determining whether Piezo2 shows nonspecific, low-level expression, which could be functionally inconsequential, or instead is expressed in highly select cell types, similar to functionally critical voltage- and transmitter-gated channel subunits expressed in the brain
3.1 Testing the sensitivity and specificity of the Anti-PIEZO2 Ab The critical requirement for our Ab generated against a human PIEZO2 peptide was high sensitivity and high selectivity in detecting the endogenous expression of the mouse ortholog Piezo2 but not its mouse paralog Piezo1
Summary
Piezo is a pressure-activated channel expressed in peripheral neurons and known to play key roles in peripheral mechanosensation [2,3,4] including the regulation of arterial blood pressure [5] and breathing [6]. One group using RT-PCR [7] and Western blotting [8] has reported Piezo expression in rat neocortical and hippocampal tissues and shown that this expression increases in response to repetitive mechanical (i.e., blast) injury These findings raise the intriguing possibility that a sudden mechanical over activation of Piezo channels caused by a concussion or mild traumatic brain injury (TBI) might contribute to the rapid and often reversible disruptions in brain functions, including loss of consciousness and memory. We were interested in determining whether Piezo shows nonspecific, low-level expression, which could be functionally inconsequential, or instead is expressed in highly select cell types, similar to functionally critical voltage- and transmitter-gated channel subunits expressed in the brain Another group, using two different anti-PIEZO2 Abs, reported Piezo expression in rat peripheral and central neurons [10]
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