This opinion manuscript outlines how the hippocampal theta rhythm could receive two
novel peripheral inputs. One of the ways this could be achieved is through Piezo2
channels and atypical hippocampal-like metabotropic glutamate receptors coupled to
phospholipase D containing proprioceptive primary afferent terminals. Accordingly,
activated proprioceptive terminal Piezo2 on Type Ia fibers synchronizes to the theta
rhythm with the help of hippocampal Piezo2 and medial septal glutamatergic neurons.
Second, after baroreceptor Piezo2 is entrained to activated proprioceptive Piezo2,
it could turn on the Cav1.3 channels, which pace the heart rhythm and regulate pacemaker
cells during cardiac sympathetic activation. This would allow the Cav1.3 channels
to synchronize to theta rhythm pacemaker hippocampal parvalbumin-expressing GABAergic
neurons. This novel Piezo2-initiated proton–proton frequency coupling through VGLUT2
may provide the ultrafast long-range signaling pathway for the proposed Piezo2 synchronization
of the low-frequency glutamatergic cell surface membrane oscillations in order to
provide peripheral spatial and speed inputs to the space and speed coding of the hippocampal
theta rhythm, supporting locomotion, learning and memory. Moreover, it provides an
ultrafast signaling for postural and orthostatic control. Finally, suggestions are
made as to how Piezo2 channelopathy could impair this ultrafast communication in many
conditions and diseases with not entirely known etiology, leading to impaired proprioception
and/or autonomic disbalance.
