Information flow in neocortical circuits is regulated by two key parameters: intrinsic neuronal properties and the short-term activitydependent plasticity of synaptic transmission. Using multineuronal whole-cell voltage recordings, we characterized the postnatal maturation of the electrophysiological properties and short-term plasticity of excitatory synaptic transmission between pairs of layer 5 (L5) pyramidal neurons (n ϭ 158) in acute slices of rat visual cortex over the first postnatal month. We found that the intrinsic and synaptic properties of L5 pyramidal neurons develop in parallel. Before postnatal day 15 (P15), intrinsic electrophysiological properties were tuned to low-frequency operation, characterized by high apparent input resistance, a long membrane time constant, and prolonged somatic action potentials. Unitary excitatory synaptic potentials were of large amplitude (P11-P15; median, 514 V), but showed pronounced use-dependent depression during prolonged regular and physiologically relevant presynaptic action potential firing patterns. In contrast, in mature animals we observed a developmental decline of the peak amplitude of unitary EPSPs (P25-P29; median, 175 V) paralleled by a decrease in apparent input resistance, membrane time constant, and somatic action potential duration. Notably, synaptic signaling of complex action potential firing patterns was also transformed, with P25-P29 connections faithfully signaling action potential trains at frequencies up to 40 Hz (1st to 50th action potential ratio, 0.91 Ϯ 0.12). Postnatal refinement of intrinsic properties and short-term plasticity therefore transforms the capacity of the L5 excitatory neural network of the visual cortex to generate and process patterns of action potential firing and contribute to network activity.

Please cite this article as: Seewoo BJ, Feindel KW, Etherington SJ, Rodger J, Frequency-specific effects of low-intensity rTMS can persist for up to 2 weeks post-stimulation: A longitudinal rs-fMRI/MRS study in rats, Brain Stimulation,

Validation of chronic restraint stress model in young adult rats for the study of depression using longitudinal multimodal MR imaging MRI-based validation of CRS depression model

Abstract-Repetitive transcranial magnetic stimulation (rTMS) has become a popular method of modulating neural plasticity in humans. Clinically, rTMS is delivered at high intensities to modulate neuronal excitability. While the high-intensity magnetic field can be targeted to stimulate specific cortical regions, areas adjacent to the targeted area receive stimulation at a lower intensity and may contribute to the overall plasticity induced by rTMS. We have previously shown that low-intensity rTMS induces molecular and structural plasticity in vivo, but the effects on membrane properties and neural excitability have not been investigated. Here we investigated the acute effect of low-intensity repetitive magnetic stimulation (LI-rMS) on neuronal excitability and potential changes on the passive and active electrophysiological properties of layer 5 pyramidal neurons in vitro. Whole-cell current clamp recordings were made at baseline prior to subthreshold LI-rMS (600 pulses of iTBS, n = 9 cells from 7 animals) or sham (n = 10 cells from 9 animals), immediately after stimulation, as well as 10 and 20 min post-stimulation. Our results show that LI-rMS does not alter passive membrane properties (resting membrane potential and input resistance) but hyperpolarises action potential threshold and increases evoked spike-firing frequency. Increases in spike firing frequency were present throughout the 20 min poststimulation whereas action potential (AP) threshold hyperpolarization was present immediately after stimulation and at 20 min post-stimulation. These results provide evidence that LI-rMS alters neuronal excitability of excitatory neurons. We suggest that regions outside the targeted region of high-intensity rTMS are susceptible to neuromodulation and may contribute to rTMS-induced plasticity. Ó