Intrinsic Cell-type Selectivity and Inter-neuronal Connectivity Alteration by Transcranial Focused Ultrasound

Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We investigate the effect of tFUS stimulation on different neuron types and synaptic connectivity in in vivo anesthetized rodent brains. Single units were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes, further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. For the first time, we show that excitatory neurons are significantly less responsive to low ultrasound pulse repetition frequencies (UPRFs), whereas the spike rates of inhibitory neurons do not change significantly across all UPRF levels. Our results suggest that we can preferentially target specific neuron types noninvasively by altering the tFUS UPRF. We also report in vivo observation of long-term synaptic connectivity changes induced by noninvasive tFUS in rats. This finding suggests tFUS can be used to encode temporally dependent stimulation paradigms into neural circuits and non-invasively elicit long-term changes in synaptic connectivity.