Time-course of changes in neuronal activity markers following iTBS-TMS of the rat neocortex

In a rat model of transcranial magnetic stimulation we could recently show that intermittent theta-burst stimulation (iTBS) affects the neocortical expression of the immediate early gene products c-Fos and zif268 as well as that of the two glutamic acid decarboxylase isoforms GAD65 and GAD67 and that of the calcium-binding proteins calbindin (CB) and parvalbumin (PV), known as markers of excitatory and inhibitory activity. We now analyzed in more detail the time course of changes in the expression of these proteins at 10, 20, 40, 80 and 160 min following a single block of iTBS consisting of 600 stimuli. Initial increase in c-Fos, zif268 and GAD65 (20 min) signals transient activation of excitatory and inhibitory neurons, thereafter first followed by a decrease in markers of activity of inhibitory neurons (GAD67, PV, CB: 20–80 min) and then by a late decrease in c-Fos and GAD65 expression (160 min). The results demonstrate that one iTBS block may have an after-effect of at least two different phases, an early phase with increased neuronal activity (c-Fos, zif268) but also the likelihood of increased GABA-release (GAD65), followed by a late phase (>40 min) of reduced neuronal activity in excitatory and inhibitory systems which may indicate a state of reduced excitability.

► We studied the expression of neuronal activity markers after iTBS rTMS in a rat model.
► Increase in c-Fos and GAD65 for 40 min signals excitatory and inhibitory activity.
► Activity markers of inhibitory neurons decrease after about 40 min.
► Late decrease in c-Fos (>120 min) reflects general cortical hypoactivity.
► iTBS rTMS drives excitatory and inhibitory neurons but leads to late hypoactivity.