Cell-type-specific bidirectional modulation of the cortico–thalamo–cortical sensory pathway by transcranial focused ultrasound (tFUS)

Abstract

Introduction Transcranial focused ultrasound (tFUS) can noninvasively modulate sensory pathways, but the cell-type-specific mechanisms underlying excitatory or inhibitory effects remain unclear. Here, we investigate how tFUS applied to the somatosensory cortex (S1) influences S1 and posterior medial thalamic nucleus (POm) responses to hind paw vibration-tactile stimulation and which neuronal populations mediate these effects. Methods Vibration-tactile stimulation evoked potentials (TEPs) and multi-unit activity (MUA) in S1 and POm were recorded from male rats. Optogenetic tagging was used to identify S1 CaMKII-positive, PV-positive, and SST-positive neurons, while waveform features were used to classify putative excitatory (i.e., regular-spiking units - RSUs) and inhibitory neurons (i.e., fast-spiking units - FSUs) in POm. Results We found that only S1 CaMKII-positive neurons and POm RSUs responded robustly to tactile stimulation. When tFUS was applied to S1, high pulse repetition frequency (PRF), high duty cycle, and high-pressure stimulation (etFUS) produced excitatory modulation of the sensory pathway, whereas low PRF, low duty cycle, and low-pressure stimulation (itFUS) induced inhibitory effects. Further analyses suggested that excitatory modulation may involve activation of S1 CaMKII-positive neurons, while the inhibitory effect may be associated with their deactivation. Conclusions These findings demonstrate that tFUS exerts bidirectional, parameter-dependent modulation of a sensory pathway and highlight the critical role of CaMKII-positive neurons in mediating these effects. This study provides mechanistic insight into cell-type-specific neuromodulation by tFUS, particularly in bidirectional modulation of a sensory pathway, and informs the optimization of stimulation parameters for targeted therapeutic interventions.

Abstract via europepmc.

Flags from extraction

• exposures[0].in_situ.pressure_kpa — Peak-to-peak pressure measured with a hydrophone beneath an ex vivo rat skull in water, not in the brain of the experimental animals; pressures 98 and 163 kPa.
• exposures[0].in_situ.ispta_w_cm2 — The text gives Ispta 32.76 and 54.49 mW/cm2 for the 1500 Hz, 30% DC condition only; the table lists other values by condition. Converted from mW/cm2 to W/cm2.
• exposures[0].unspecified_domain.isppa_w_cm2 — Isppa (109.2 and 181.63 mW/cm2) is taken from Table 1 with no domain stated; converted to W/cm2.
• exposures[0].timing.pulse_duration_ms — Figure legend says pulse duration was calculated from PRF and DC; no value stated, so not recorded.
• exposures[0].timing.pulse_repetition_frequency_hz — Text and Table 1 also include a 30 Hz/60% and 3 kHz/0.6% condition, and 1500 Hz/30% appears in Table 1 and the in situ sentence; list is of PRFs seen.
• exposures[0].timing.sonication_duration_s — 100 ms with vibration; 67 ms for tFUS only.
• sham_type — No sham ultrasound; tactile stimulation alone served as the comparison within the same animals.
• auditory_control — Discussion argues auditory confound is unlikely citing prior work; no control in this study.
• n_subjects — N = 34 rats for tactile responses; virus groups N = 10, 12, 12 (sum 34). Not all rats received every tFUS condition.