Position Sense, Proprioception, Memory in Light of Piezo2 Channelopathy as Traumatic Brain Injury and Alzheimer’s Disease Show

Recent re-examination of the gravity-dependency of position sense revealed two distinctive proprioceptive pathway generation. One was indeed gravity-dependent as matching and pointing tasks showed, while the other one was suggested to use memory as repositioning demonstrated it in a gravity-independent fashion. The current manuscript puts forward that not only matching and pointing tasks use muscle spindle-dependent position sense, but repositioning as well. Consequently, memory-supported repositioning does not involve peripheral proprioceptor encoding acutely in the context of scene representations, however spatial and episodic memory with critical hippocampal contribution may essentially rely on earlier peripheral intrafusal proprioceptive Piezo2-initiated input source through hippocampal learning and memory. Furthermore, the cingulate cortex and working memory may be involved in this memory process downstream. Accordingly, the underlying proposed two distinctive proprioceptive pathways are the following: the muscle spindle-derived proprioceptive terminal Piezo2-initiated ultrafast signaling may contribute to motoneurons in a monosynaptic fashion through VGLUT1 and to the hippocampus as well through VGLUT2. Delayed onset muscle soreness, with the theorized microdamage of these proprioceptive terminals, impairs the efficiency of proprioceptive integration and body representation process during body-related motor imagery. Body representation is indeed crucial in spatial, episodic and working memory formation. This manuscript puts into perspective how the microdamage of Piezo2 on these proprioceptive terminals may not only miswire proprioception acutely, like in delayed onset muscle soreness, but with chronification as well, leading to spatial, episodic and working memory impairments, and rapid eye movement sleep reduction. This longitudinal trajectory is demonstrated mainly though traumatic brain injury and Alzheimer’s disease.