Temporal Structure of Neuronal Activity among Cortical Neuron Subtypes during Slow Oscillations in Anesthetized Rats

Slow-wave oscillations, the predominant brain rhythm during sleep, are composed of Up/Down cycles. Depolarizing Up-states involve activity in layer 5 (L5) of the neocortex, but it is unknown how diverse subtypes of neurons within L5 participate in generating and maintaining Up-states. Here we compare the in vivo firing patterns of corticopontine (CPn) pyramidal cells, crossed-corticostriatal (CCS) pyramidal cells, and fast-spiking (FS) GABAergic neurons in the rat frontal cortex, with those of thalamocortical neurons during Up/Down cycles in the anesthetized condition. During the transition from Down- to Up-states, increased activity in these neurons was highly temporally structured, with spiking occurring first in thalamocortical neurons, followed by cortical FS cells, CCS cells, and, finally, CPn cells. Activity in some FS, CCS, and CPn neurons occurred in phase with Up-nested gamma rhythms, with FS neurons showing phase delay relative to pyramidal neurons. These results suggest that thalamic and cortical pyramidal neurons are activated in a specific temporal sequence during Up/Down cycles, but cortical pyramidal cells are activated at a similar gamma phase. In addition to Up-state firing specificity, CCS and CPn cells exhibited differences in activity during cortical desynchronization, further indicating projection- and state-dependent information processing within L5.

Patterned activity in neocortical electroencephalograms, including slow waves and gamma oscillations, is thought to reflect the organized activity of neocortical neurons that comprises many specialized neuron subtypes. We found that the timing of action potentials during slow waves in individual cortical neurons was correlated with their laminar positions and axonal targets. Within gamma cycles nested in the slow-wave depolarization, cortical pyramidal cells fired earlier than did interneurons. At the start of slow-wave depolarizations, activity in thalamic neurons receiving inhibition from the basal ganglia occurred earlier than activity in cortical neurons. Together, these findings reveal a temporally ordered pattern of output from diverse neuron subtypes in the frontal cortex and related thalamic nuclei during neocortical oscillations.