Multiple blocks of intermittent and continuous theta‐burst stimulation applied via transcranial magnetic stimulation differently affect sensory responses in rat barrel cortex

Abstract

Cortical sensory processing varies with cortical state and the balance of inhibition to excitation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate human cortical excitability. In a rat model, we recently showed that intermittent theta-burst stimulation (iTBS) applied to the corpus callosum, to activate primarily supragranular cortical pyramidal cells but fewer subcortical neurons, strongly reduced the cortical expression of parvalbumin (PV), indicating reduced activity of fast-spiking interneurons. Here, we used the well-studied rodent barrel cortex system to test how iTBS and continuous TBS (cTBS) modulate sensory responses evoked by either single or double stimuli applied to the principal (PW) and/or adjacent whisker (AW) in urethane-anaesthetized rats. Compared to sham stimulation, iTBS but not cTBS particularly enhanced late (>18 ms) response components of multi-unit spiking and local field potential responses in layer 4 but not the very early response (<18 ms). Similarly, only iTBS diminished the suppression of the second response evoked by paired PW or AW–PW stimulation at 20 ms intervals. The effects increased with each of the five iTBS blocks applied. With cTBS a mild effect similar to that of iTBS was first evident after 4–5 stimulation blocks. Enhanced cortical c-Fos and zif268 expression but reduced PV and GAD67 expression was found only after iTBS, indicating increased cortical activity due to lowered inhibition. We conclude that iTBS but less cTBS may primarily weaken a late recurrent-type cortical inhibition mediated via a subset of PV+ interneurons, enabling stronger late response components believed to contribute to the perception of sensory events.

Assessment and modulation of cortical inhibition using transcranial magnetic stimulation

“…Similar correlations between PV expression and the balance of excitatory and inhibitory synaptic inputs were earlier described in the hippocampus of mice (Donato et al, 2013). Another electrophysiological study in the primary somatosensory cortex of rats further demonstrates that a decrease of PV expression, induced by iTBSrTMS, is accompanied by an increase of sensory responses (Thimm and Funke, 2015). This observation supports the notion that rTMS-induced disinhibition could underlie the previously described improvement in learning behaviour (Mix et al, 2010).…”

The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy

“…37 In other stimulation paradigms however, like theta burst stimulation, decrease in PRV-ir has been shown after stimulation, although this effect seemed to depend on the timing and pattern of stimulation. 38 …”

Untersuchung und Modulation kortikaler Inhibition mittels transkranieller Magnetstimulation

“…Ähnliche Zusammenhänge zwischen PV-Expression und der Balance erregender zu hemmenden synaptischen Eingängen wurden auch im Hippokampus von Mäusen beschrieben (Donato et al 2013). Eine elektrophysiologische Studie im primären somatosensorischen Kortex der Ratte zeigte dann auch, dass eine durch iTBS-rTMS-induzierte Abnahme der PV-Expression von einer Steigerung sensorischer Antworten begleitet ist (Thimm und Funke 2015), die ursächlich für die zuvor beschriebene Steigerung der Lernleistung sein könnte (Mix et al 2010), sodass diese Studien das Model der rTMS-induzierten Disinhibition stützen. Allerdings lassen Untersuchungen inhibitorischer Aktivitäts-und Plastizitätsmarker nur indirekte Aussagen über rTMS-induzierte funktionelle Veränderungen inhibitorischer Synapsen zu.…”