Pressure Pulsatility Links Cardio-Respiratory and Brain Rhythmicity

This article presents evidence indicating that intracranial pressure (ICP) pulsatility, associated with the heartbeat and breathing, is not just a source of mechanical artefact in electrical recordings, but is “sensed” and plays a role in the brain’s information processing. Patch-clamp recording of pressure-activated channels, and detection of Piezo2-protein channel expression in brain neurons, suggest that these channels provide neurons with an intrinsic resonance to ICP pulsatility, which acts to synchronize remote neural networks. Direct measurements in human patients indicate that heartbeat and breathing rhythms generate intracranial forces of tens of millinewtons, exceeding by orders of magnitude the localized forces shown by atomic force microscopy and optical tweezers to activate Piezo channels in isolated neocortical and hippocampal neurons. Additionally, many human touch and proprioceptors, which are also transduced by Piezo channels, show spiking that is phase-locked to heartbeat- and breathing-induced extracranial pressure pulsations. Finally, based on the observation that low-frequency oscillations modulate the phase and amplitude of high-frequency oscillations, body and brain oscillations are proposed to form a single hierarchical system in which the heartbeat is the basic frequency and scaling factor for all other oscillations. Together, these results support the idea that ICP pulsatility may be elemental in modulating the brain’s electrical rhythmicity.

Keywords

heartbeat- and breathing-induced intracranial pressure pulsatility

millinewton pulsatile forces

brain neurons

pressure-activated Piezo channels

neural network entrainment

electroencephalogram (EEG)

electrical rhythmicity

proprioceptors

touch receptors

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Fig. 1.

Pressure-activated single channel currents trigger spiking in mouse hippocampal and neocortical pyramidal neurons. The top traces in (A–D) show the applied negative pressure pulse waveforms. (A) The lower trace is the cell-attached patch-current recorded from a mouse hippocampal pyramidal neuron indicating “spontaneous” brief ( $<$ 1 ms) inward currents that displayed the same unitary amplitude (~5 pA, see dashed line) as the 20-mmHg pressure pulse activated current “bursts” that also triggered outward current spikes (i.e., action potentials in the whole neuron). (B) The lower trace is the current recorded from the same patch as in (A), with V ${}_{\text{pip}}$ increased from 50 mV to 70 mV. In this case indicating that spontaneous inward channel current bursts (**) can trigger individual spikes (*). Pipette solution: divalent-free, 120 mM KCl, with an estimated single channel conductance of ~60 pS over the patch potential range of –100 mV to –120 mV. (C) The lower trace is the current recorded from a mouse neocortical pyramidal neuron. The two pressure pulses (40 and 30 mmHg) activated multiple channel inward currents (–13 pA and –10 pA) that triggered spiking (at 9 Hz and 8 Hz). (D) The lower trace is the current recorded from the same patch as in (C) with V ${}_{\text{pip}}$ increased from 40 mV to 75 mV. In this case a smaller pressure pulse (20 mm Hg) activated a single channel opening that triggered 9 spikes at ~5 Hz. In both traces in (C,D) there were spontaneous spikes (*) that were not triggered by inward currents, at least as recorded in the patch. On the other hand, brief spontaneous inward currents (**) that were evident in this trace, failed to trigger a spike. Modified from Ref. [16] Brain Research, Nikolaev YA, Dosen PJ, Laver DR, van Helden DF, Hamill OP. Single mechanically gated cation channel currents can trigger action potentials in neocortical and hippocampal pyramidal neurons. 1608, 1–13, (2015), with permission from Elsevier.

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J. Integr. Neurosci. Print ISSN 0219-6352 Electronic ISSN 1757-448X