Intermittent theta burst transcranial magnetic stimulation induces hippocampal mossy fibre plasticity in male but not female mice

Abstract

Transcranial magnetic stimulation (TMS) induces electric fields that depolarise or hyperpolarise neurons. Intermittent theta burst stimulation (iTBS), a patterned form of TMS that is delivered at the theta frequency ($5 Hz), induces neuroplasticity in the hippocampus, a brain region that is implicated in memory and learning. One form of plasticity that is unique to the hippocampus is adult neurogenesis; however, little is known about whether TMS or iTBS in particular affects newborn neurons. Here, we therefore applied repeated sessions of iTBS to male and female mice and measured the extent of adult neurogenesis and the morphological features of immature neurons. We found that repeated sessions of iTBS did not significantly increase the amount of neurogenesis or affect the gross dendritic morphology of new neurons, and there were no sex differences in neurogenesis rates or aspects of afferent morphology. In contrast, efferent properties of newborn neurons varied as a function of sex and stimulation. Chronic iTBS increased the size of mossy fibre terminals, which synapse onto Cornu Ammonis 3 (CA3) pyramidal neurons, but only in males. iTBS also increased the number of terminal-associated filopodia, putative synapses onto inhibitory interneurons but only in male mice. This efferent plasticity could result from a general trophic effect, or it could reflect accelerated maturation of immature neurons. Given the important role of mossy fibre synapses in hippocampal learning, our results identify a neurobiological effect of iTBS that might be associated with sex-specific changes in cognition.