Dose-response relationship between the variables of unilateral optogenetic stimulation and transcallosal evoked responses in rat motor cortex

Abstract

Efficient interhemispheric integration of neural activity between left and right primary motor cortex (M1) is critical for inter-limb motor control. We employed optogenetic stimulation to establish a framework for probing transcallosal M1–M1 interactions in rats. We performed optogenetic stimulation of excitatory neurons in right M1 of male Sprague-Dawley rats. We recorded the transcallosal evoked potential in contralateral left M1 via chronically implanted electrodes. Recordings were performed under anesthesia combination of dexmedetomidine and a low concentration of isoflurane. We systematically varied the stimulation intensity and duration to characterize the relationship between stimulation parameters in right M1 and the characteristics of the evoked intracortical potentials in left M1. Optogenetic stimulation of right M1 consistently evoked a transcallosal response in left M1 with a consistent negative peak (N1) that sometimes was preceded by a smaller positive peak (P1). Higher stimulation intensity or longer stimulation duration gradually increased N1 amplitude and reduced N1 variability across trials. A combination of stimulation intensities of 5–10 mW with stimulus durations of 1–10 ms were generally sufficient to elicit a robust transcallosal response in most animal, with our optic fiber setup. Optogenetically stimulated excitatory neurons in M1 can reliably evoke a transcallosal response in anesthetized rats. Characterizing the relationship between “stimulation dose” and “response magnitude” (i.e., the gain function) of transcallosal M1-to-M1 excitatory connections can be used to optimize the variables of optogenetic stimulation and ensure stimulation efficacy.

Mapping axon diameters and conduction velocity in the rat brain – different methods tell different stories of the structure-function relationship

“…The recorded LFP data was further filtered with a notch filter at 50 Hz and a 2 nd order Butterworth band-pass filter between 3 Hz and 300 Hz. For further details, see the previous study 45 .…”

“…All animal procedures were conducted in accordance with the ARRIVE guidelines, the European Communities Council Directive (2010/63/EU) and were approved by the Animal Experiments Inspectorate (2016-15-0201-00868) of Denmark. The electrophysiological raw data were collected as part of our previous study [36], where detailed methods can be found. The data was reanalyzed in the present study to obtain the TCT.…”

“…The mean (± SD) depth of 1045.23 ± 47.55 µm (N=5; Supplementary Table 2) suggests that depth variation was negligible. [36] in reliable conditions, with a coefficient of variation for the N1 peak being < 1.00. Colors correspond to the insert in subfigure (a).…”

“…Four to seventeen weeks after surgery, the animals were exposed to a paradigm of blue laser light brain stimulation (𝛌 = 447 nm) while recording the evoked responses as LFPs. Prior to the experiment, the animals had been anesthetized with dexmedetomidine and low dose isoflurane, as described in our previous study 45 . The available data from 45 included systematically varied stimulation durations and intensities (0.1-10.0 ms and 0.25-10 mW), resulting in a stimulation input parameter map of 42 different conditions.…”

“…Prior to the experiment, the animals had been anesthetized with dexmedetomidine and low dose isoflurane, as described in our previous study 45 . The available data from 45 included systematically varied stimulation durations and intensities (0.1-10.0 ms and 0.25-10 mW), resulting in a stimulation input parameter map of 42 different conditions. Each condition produced 150 individual trials, totaling 6300 stimuli per animal, with a few (< 8 trials per condition) being discarded for technical reasons.…”