TRANSCUTANEOUS ELECTRIC AND CHEMOGENETIC SPINAL CORD STIMULATION MODULATE MEMORY CAPACITY IN MICE

Experimental studies in healthy humans and cognitively impaired patients have shown that transpinal (tsDCS) and transcutaneous (tcDCS) direct current stimulation improve memory. However, the neurobiological mechanisms involved remain to be explored. To investigate these mechanisms, we implemented two parallel approaches in mice. First, to mimic the effects of tsDCS in humans, we employed intra-spinal injections of an activatory chemogenetic tool – Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) – that after injection of the exogenous ligand clozapine-N-oxide activated excitatory spinal neurons in the learning phase of a memory capacity task sensitive to subtle changes. Spinal activation selectively improved high-load memory performance, while having no impact on low-load memory, locomotor activity, anxiety, and pain.
Second, to parallel tcDCS in humans, we applied anodal transcutaneous electrical stimulation over dorsal thoracic segments during the post-learning phase of the same memory task. To test the pro-cognitive rescue potential of tcDCS, mice were either post-learning anaesthetised to induce a transient memory consolidation impairment or anaesthetised and simultaneously stimulated with tcDCS (1 mA, continuous stimulation). While anaesthetised mice exhibited a memory impairment, tcDCS-stimulated mice showed a memory performance comparable to that of control non-anaesthetised mice. This preliminary evidence indicates that spinal and peripheral stimulation can enhance memory processing. Ongoing experiments aim to elucidate the central brain mechanisms underpinning these effects. Overall, our results pave the way to a deeper exploration of the role of brain-body interactions mediated by the spinal cord and suggest the implication of the somatosensory system in neuromodulation of cognitive functions.