Abstracts

RATIONALE: Neocortical circuits contain a large diversity of interneurons whose role in normal cortical processing remains poorly understood. We have recently characterized two main classes of interneurons in layer 4 of neocortex: low-threshold spiking (LTS) cells, and fast-spiking (FS) cells. Electrical synapses were found to be common between neurons of the same type, but rare between neurons of different type. Coupling was strong enough to synchronize spiking of electrically coupled cells. Here, we characterized the short-term dynamics of excitatory synapses onto the two types of interneurons and tested their sensitivity to neuromodulators, in order to better understand whether distinct interneuron networks are specifically activated by different patterns of cortical activity. METHODS: Dual whole-cell recordings were performed in layer 4 of barrel cortex, in rat thalamocortical slices, at ages P14 to P21. The metabotropic glutamate receptor agonist ACPD and muscarine were bath applied. RESULTS: LTS cells were targeted by excitatory synapses that showed strong, frequency-dependent short-term facilitation. In contrast, excitatory input onto FS cells displayed short-term depression at all frequencies tested. The application of ACPD or muscarine resulted in synchronous firing and subthreshold oscillations specifically in LTS neurons. This acitivity was maintained in the presence of blockers of fast synaptic transmission. Synchrony was maintained in a spatial domain of about 400 ?m in diameter. LTS activity strongly correlated with IPSPs in neighboring FS interneurons and excitatory neurons. The effects of drug application could be mimicked by local tetanic stimulation. CONCLUSIONS: High frequency cortical activity will specifically activate LTS interneurons, via facilating synapses and the stimulation of postsynaptic metabotropic receptors. Therefore, the network of LTS cells is likely to play a crucial role in controlling high-frequency cortical activity that could otherwise promote seizure-like events. Supported by the Burroughs-Wellcome Trust and NIH (NS10478 and NS25983).