Piezo2—peripheral baroreceptor channel expressed in select neurons of the mouse brain: a putative mechanism for synchronizing neural networks by transducing intracranial pressure pulses

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.

Likely Pathogenic Variants of Cav1.3 and Nav1.1 Encoding Genes in Amyotrophic Lateral Sclerosis Could Elucidate the Dysregulated Pain Pathways

“…In addition, it is theorized that the dysfunctional spinal microcircuits of ALS are progressively interfering with the synchronization of central pattern generators (CPG) [ 18 ], such as locomotion, and the aforementioned rhythmic firing feature of the Ca v 1.3 ion channels could be involved in this process. It is noteworthy that animal research demonstrates that Piezo2 indeed has a role in synchronizing neural networks supraspinally [ 42 ], and it might be the case spinally as well. Hence, the lost function of excitatory Piezo2 in ALS could lead to the theorized impairment of the spinal synchronization of CPGs and to the lost function of the spinal Ca v 1.3 ion channels.…”

LF Power of HRV Could Be the Piezo2 Activity Level in Baroreceptors with Some Piezo1 Residual Activity Contribution

“…Research is emerging about the pressure pulse-detecting capability of Piezo2 via baroreceptors and its abrupt mechanotransmission, unlike neurotransmitter-based detection, throughout the supraspinal level [ 28 ]. This supraspinal detection and mechanotransmission may be analogous to that reported by Zeng et al on the periphery, where Piezo2 channels of the baroreceptors detect BP and contribute to the baroreceptor baroreflex on the spinal level [ 8 ].…”

Mechanosensitive Piezo channels mediate the physiological and pathophysiological changes in the respiratory system

“…Obstructive sleep apnea/ hypopnea syndrome (OSAHS) leads to a decrease in intracranial blood oxygen concentration and damages hippocampal neurons. Piezo2 expressed in the hippocampus might explain the relationship between the brain and the respiratory system [ 70 ]. However, existing evidence does not prove that OSAHS is related to the expression of Piezo2 in the hippocampus.…”