6 × the resting motor threshold). Navigated brain stimulation was used to monitor

the coil position. A linear relationship was observed between test peak size and test TMS intensity, reflecting linear summation of excitatory inputs induced by TMS. SICI was estimated using the difference between conditioned (produced by the paired pulses) and test Venetoclax peaks (produced by the isolated test pulse). Although the conditioning intensity (activating cortical inhibitory interneurons mediating SICI) was kept constant throughout the experiments, the level of SICI changed with the test peak size, in a non-linear fashion, suggesting that low-threshold cortical neurons (excitatory interneurons/pyramidal cells) are less sensitive to SICI than those of higher threshold. These findings provide the first experimental evidence, IWR-1 in vitro under physiological conditions, for non-linear input/output properties of a complex cortical network. Consequently, changes in the recruitment gain of cortical inhibitory interneurons can greatly modify the excitability of pyramidal cells and their response to afferent inputs. Recent advances in transcranial magnetic stimulation (TMS) have provided an indirect electrophysiological approach to human cortical networks (Hallett, 2007). In the paired pulse paradigms (Kujirai et al., 1993), a first (conditioning) TMS pulse modifies cortex excitability and influences the pyramidal cell transynaptic response to a second (test) pulse.

The motor-evoked potential (MEP), commonly used to evaluate cortical excitability, is influenced

by the conditions of electromyographic (EMG) recording and the spinal motoneurons participating in its amplitude (Lackmy & Marchand-Pauvert, 2010). In the same way, short-interval intracortical inhibition (SICI) depends on the size of the MEP evoked by an isolated test pulse, partly due to the origin of the TMS-induced corticospinal volleys (direct D-wave vs. indirect late I-waves; Garry & Thomson, 2009). The relationship between SICI and MEP size was also attributed to the spinal motoneuron properties, and probably to non-linear summation at cortical level, but the latter was difficult to estimate using variations in MEP amplitude (Lackmy & Marchand-Pauvert, 2010). Given the heterogeneous motoneuron pool properties and the different sensitivity of the corticospinal volleys to SICI, it is difficult Diflunisal to distinguish the effects at cortical and spinal level. A method testing SICI on a single motoneuron and a single corticospinal volley, to avoid the effect due to their own properties, would be required to clarify summation at cortical level. Complex neural networks mediate the information in the cerebral cortex to pyramidal cells, whose intrinsic properties (Spruston, 2008) and synaptic input characteristics (DeFelipe & Fariñas, 1992) influence their input–output properties. Both electrophysiological (Oviedo & Reyes, 2005; Williams, 2005) and computational (Poirazi et al.