Optogenetic fMRI investigation of the spatiotemporal characteristics of the somatosensory thalamocortical circuit

Abstract

The somatosensory thalamocortical system is an integral part in processing somatosensory information relayed by the peripheral nervous system. The lemniscal projection in particular is relayed through the ventral posteromedial nucleus (VPM) to the primary somatosensory cortex (S1). Previous electrophysiological studies stimulating the VPM and the lemniscal fibers in rodents have demonstrated the effect of frequency on the propagation of electrical activity to S1. However, the effects of stimulation frequency beyond S1 remain unknown and previous studies were limited by the non-cell-type specific electrical stimulation. Hence, optogenetic functional magnetic resonance imaging (ofMRI) is used to provide whole-brain 4D coverage and address the issue of non-cell-type-specificity. To enable selective optogenetic control of VPM thalamocortical excitatory neurons, CaMKIIα-channelrhodopsin-encoding virus was injected into the VPM of adult male Sprague-Dawley rats. Four stimulation frequencies (1, 5, 10 and 20 Hz) were used to determine the spatiotemporal dynamics of blood oxygen-level dependent (BOLD) response. Stimulation at all four frequencies resulted in BOLD responses in S1 and the secondary somatosensory cortex (S2) that increases spatially as stimulation frequency decreases. Differences in the BOLD profile temporally at S1 and S2 were also observed when comparing 5, 10 and 20 Hz to 1 Hz stimulation. Intriguingly, large-scale cortical BOLD responses were detected beyond S1 and S2, namely at the visual (VC) and auditory (AC) cortex during 1 Hz stimulation. Intracortical local field potential (LFP) recordings were then performed at S1 and bilateral VC in different animals guided by the ofMRI results. Recordings showed close correlation to the BOLD cortical responses in terms of their overall temporal characteristics at all stimulation frequencies. LFP latency measurements of evoked responses during 1 Hz stimulation indicated that the response was first evoked in S1, followed by the ipsilateral VC and lastly the contralateral VC. It implies that such large-scale cortical response has a multi-synaptic basis of activity propagation. These results suggest that despite VPM being a highly specific thalamic relay in the somatosensory circuit, it is possible that low frequency stimulation, 1 Hz of VPM enables the recruitment of bilateral VC and AC via S1’s long-range intrahemispheric cortical projections and subsequent commissural projections at ipsilateral VC and AC. Altogether, ofMRI has revealed the specificity of frequency in governing thalamocortical activity and highlighted its use in studying mechanisms of large-scale brain circuitry.