Theta burst and conventional low-frequency rTMS differentially affect GABAergic neurotransmission in the rat cortex

Abstract

Modified cortical excitability following repetitive transcranial magnetic stimulation (rTMS) may be related to short- or long-term synaptic plasticity of neuronal excitation but could also affect cortical inhibition. Therefore, in the rat we tested how three different rTMS protocols, intermittent and continuous theta-burst (iTBS, cTBS), and low-frequency 1 Hz stimulation, change the expression of GAD65, GAD67 and GAT-1 which are expressed in cortical inhibitory interneurons in an activity-dependent manner. Acutely (2 h), all protocols reduced the expression of GAD67 in frontal, motor, somatosensory and visual cortex but increased that of GAD65 and GAT-1 to different degree, with iTBS having the strongest acute effect. The initial decrease in GAD67 reversed after 1 day, leading to a strong increase in GAD67 expression for up to 7 days primarily in the frontal cortex in case of iTBS, cTBS and in all studied areas following 1 Hz rTMS. While also GAD65 and GAT-1 expression reversed after 1 day in case of iTBS and cTBS, 1 Hz rTMS induced a steady increase in GAD65 and GAT-1 expression during the 7 days investigated. Our data demonstrate that rTMS affects the expression of activity-dependent proteins of the cortical inhibitory interneurons. Besides common effects of low- (1 Hz) and high-frequency (TBS) stimulation on protein expression, differences in quantity and time course of changes point to differences in the contribution of possible neuronal subsystems. Further studies are needed to distinguish cell-type specific effects.

Theta-Burst Transcranial Magnetic Stimulation Alters Cortical Inhibition

“…Strengthened recurrent inhibition would then result in a stronger intracortical suppression of sensory activity following at short delays (increase in PPAI). A strengthening of the GABAergic synapses by iTBS is further supported by our recent finding of increased GAD65 expression following iTBS and cTBS (Trippe et al, 2009), which is indicative of enhanced presynaptic GABA-synthesis and release, while the reduction in GAD67 supports the general hypoactivation of inhibitory neurons.…”

Investigations of motor-cortex cortical plasticity following facilitatory and inhibitory transcranial theta-burst stimulation in schizophrenia: A proof-of-concept study

“…Furthermore, other animal studies show that both TBS patterns increase GAD65, but reduce GAD67 expression, indicating increased activation and short-term plasticity of GABAergic synapses (Funke and Benali, 2011;Trippe et al, 2009). Human investigation of the shortlatency intracortical inhibition (SICI) (Kujirai et al, 1993), an inhibitory paradigm likely acting via GABA A -interneurons (Ziemann, 2004), showed that cTBS600 at different stimulation intensities reduces SICI after stimulation (Huang et al, 2005;McAllister et al, 2009).…”

Repetitive transcranial magnetic stimulation and drug addiction

“…Furthermore, it has been demonstrated that rTMS increases dopamine in the dorsal hippocampus (Keck et al, 2002) and the nucleus accumbens (Erhardt et al, 2004;Keck et al, 2002) using microdialysis in rodents. Repetitive TMS in the rat has also been shown to change the expression of proteins refl ected by the synthesis of γ -aminobutyric acid (GABA) by two isoforms of GAD (Trippe et al, 2009). That is, Trippe et al demonstrated that 1 Hz rTMS in the rat reduced expression of GAD67 and increased the expression of GAD65 and GABA transporter (GAT-1) compared to sham stimulation (Trippe et al, 2009).…”

“…Repetitive TMS in the rat has also been shown to change the expression of proteins refl ected by the synthesis of γ -aminobutyric acid (GABA) by two isoforms of GAD (Trippe et al, 2009). That is, Trippe et al demonstrated that 1 Hz rTMS in the rat reduced expression of GAD67 and increased the expression of GAD65 and GABA transporter (GAT-1) compared to sham stimulation (Trippe et al, 2009). In humans, rTMS has been shown to induce changes in cortical inhibition.…”