Sequential activation of microcircuits underlying somatosensory-evoked potentials in rat neocortex.

Evoked cortical field potentials are widely used in neurophysiological studies into cortical functioning, but insight in the underlying neural mechanisms is severely hampered by ambiguities in the interpretation of the field potentials. The present study aimed at identifying the precise relationships between the primary evoked cortical field potential (the positive-negative [P1-N1]response) and the temporal and spatial sequence in which different local cortical micro-circuits are recruited. We electrically stimulated the median nerve and recorded field potentials using a 12-channel depth probe in somatosensory cortex of ketamine anesthetized rats. Current source density analysis was used and a grand average was constructed based on all individual animals taking into account individual differences in cortical layering. Manipulation of stimulus strength, selective averaging of single trial responses, and double-pulse stimulation, were used to help disentangle overlapping dipoles and to determine the sequence of neuronal events. We discriminated three phases in the generation of the P1-N1 wave. In the first phase, specific thalamic afferents depolarize both layer III and layer V pyramidal cells. In the second phase, superficial pyramidal cells are depolarized via supragranular intracortical projections. In the third phase, population spikes are generated in layer Vb pyramidal cells, associated with a distinct fast (approximately 1 ms) sink/source configuration. Axon-collaterals of layer Vb pyramidal cells produce an enhanced activation of the supragranular pyramidal cells in layer I-II, which generates N1.