Focal transcranial magnetic stimulation in awake rats: Enhanced glucose uptake in deep cortical layers

Abstract

Background: Transcranial magnetic stimulation (TMS) is an emerging neuromodulation tool. However, preclinical models of TMS are limited.

Objective: To develop a method for performing TMS in awake rats and to characterize neuronal response to TMS by mapping glucose uptake following TMS administration.

Methods: A headpost was implanted into rat skull serving as a refence to guide TMS target. Motor threshold measurement was used as the metric to assess the consistency in TMS delivery across animals and across sessions. Using a fluorescent glucose analogue (2-NBDG) as a marker of neuronal activity, we mapped glucose uptake in response to TMS of the rat motor cortex.

Results: The average motor threshold (n = 41) was 34.6 ± 6.3 % of maximum stimulator output (MSO). The variability of motor threshold across animals was similar to what has been reported in human studies. Furthermore, there was no significant difference in motor threshold measured across 3 separate days. Enhancement in fluorescent signals were TMS dose (power)-dependent, which centered around the motor cortex, covering an area medial-laterally 2 mm, rostral-caudally 4 mm at 55 % MSO, and 3 mm at 35 % MSO. The count of total cells with significant fluorescent signal was: 107 ± 23 (55 % MSO), 73 ± 11 (35 % MSO) and 42 ± 11 (sham, 5% MSO).

Conclusions: Our method allows for consistent motor threshold assessment for longitudinal studies. Notably, cells with fluorescent signal enhancement were consistently aggregated in deep cortical layers, with minimal enhancement in superficial layers COMPARISONS WITH EXISTING METHOD(S): To our knowledge, this is the first study of focal TMS in awake rodents.

Keywords: 2-DG; 2-NBDG; Fluorescence; Focal TMS; Glucose.