During behavioral quiescence, the neocortex generates spontaneous slow oscillations that consist of Up and Down states. Up states are short epochs of persistent activity that resemble the activated neocortex during arousal and cognition. Although Up states are generated within the cortex, the impact of extrinsic (thalamocortical) and intrinsic (intracortical) inputs on the persistent activity is not known. Using thalamocortical slices, we found that the persistent cortical activity during spontaneous Up states effectively drives thalamocortical relay cells through corticothalamic connections. However, thalamic activity can also precede the onset of cortical Up states, which suggests a role of thalamic activity in triggering cortical Up states through thalamocortical connections. In support of this hypothesis, we found that cutting the connections between thalamus and cortex reduced the incidence of spontaneous Up states in the cortex. Consistent with a facilitating role of thalamic activity on Up states, electrical or chemical stimulation of the thalamus triggered cortical Up states very effectively and enhanced those occurring spontaneously. In contrast, stimulation of the cortex triggered Up states only at very low intensities but otherwise had a suppressive effect on Up states. Moreover, cortical stimulation suppressed the facilitating effect of thalamic stimulation on Up states. In conclusion, thalamocortical inputs facilitate and intracortical inputs suppress cortical Up states. Thus, extrinsic and intrinsic cortical inputs differentially regulate persistent activity, which may serve to adjust the processing state of thalamocortical networks during behavior.
During disinhibition the neocortex generates synchronous activities. In neocortical slices application of GABA A and GABA B receptor antagonists transformed slow oscillations into large amplitude spike-wave discharges that contained a rhythmic ~10 Hz neocortical oscillation. The 10 Hz oscillations caused by disinhibition were highly region specific and were generated only in frontal agranular regions of neocortex, such as the primary motor cortex, but not in granular neocortex. Pharmacological manipulations showed that the 10 Hz oscillations were critically dependent on a-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. Current source density (CSD) analyses in slices using 16-site silicon probes revealed that the 10 Hz oscillations were expressed with large current sinks in the upper layers and smaller current sinks in the lower layers that precede them. The results indicate that blocking GABA B receptors in the agranular neocortex unmasks recurrent synaptic activity mediated by AMPA receptors that results in the generation of these oscillations. Journal of PhysiologyThe results show that disinhibition induces 10 Hz oscillations in agranular, but not granular neocortex. Pharmacological manipulations demonstrate that blocking AMPA receptors, but not any other glutamate receptor, completely abolishes the 10 Hz oscillations leaving intact the spike-wave discharges caused by blocking GABA A receptors alone. Finally, current source density (CSD) analysis reveals that the 10 Hz oscillations are strongly expressed in the upper layers, perhaps as a result of preceding activity in the lower layers.
The motor cortex generates synchronous network oscillations at frequencies between 7 and 14 Hz during disinhibition or low [Mg 2+ ] o buffers, but the underlying mechanisms are poorly understood. These oscillations, termed here ∼10 Hz oscillations, are generated by a purely excitatory network of interconnected pyramidal cells because they are robust in the absence of GABAergic transmission. It is likely that specific voltage-dependent currents expressed in those cells contribute to the generation of ∼10 Hz oscillations. We tested the effects of different drugs known to suppress certain voltage-dependent currents. The results revealed that drugs that suppress the low-threshold calcium current and the hyperpolarization-activated cation current are not critically involved in the generation of ∼10 Hz oscillations. Interestingly, drugs known to suppress the persistent sodium current abolished ∼10 Hz oscillations. Furthermore, blockers of K + channels had significant effects on the oscillations. In particular, blockers of the M-current abolished the oscillations. Also, blockers of both non-inactivating and slowly inactivating voltage-dependent K + currents abolished ∼10 Hz oscillations. The results indicate that specific voltage-dependent non-inactivating K + currents, such as the M-current, and persistent sodium currents are critically involved in generating ∼10 Hz oscillations of excitatory motor cortex networks.
The neocortex generates short epochs of persistent activity called up states, which are associated with changes in cellular and network excitability. Using somatosensory thalamocortical slices, we studied the impact of persistent cortical activity during spontaneous up states on intrinsic cellular excitability (input resistance) and on excitatory synaptic inputs of cortical cells. At the intrinsic excitability level, we found that the expected decrease in input resistance (high conductance) resulting from synaptic barrages during up states is counteracted by an increase in input resistance due to depolarization per se. The result is a variable but on average relatively small reduction in input resistance during up states. At the synaptic level, up states enhanced a late synaptic component of short-latency thalamocortical field potential responses but suppressed intracortical field potential responses. The thalamocortical enhancement did not reflect an increase in synaptic strength, as determined by measuring the evoked postsynaptic current, but instead an increase in evoked action potential (spike) probability due to depolarization during up states. In contrast, the intracortical suppression was associated with a reduction in synaptic strength, apparently driven by increased presynaptic intracortical activity during up states. In addition, intracortical suppression also reflected a reduction in evoked spike latency caused by depolarization and the abolishment of longer-latency spikes caused by stronger inhibitory drive during up states. In conclusion, depolarization during up states increases the success of excitatory synaptic inputs to reach firing. However, activity-dependent synaptic depression caused by increased presynaptic firing during up states and the enhancement of evoked inhibitory drive caused by depolarization suppress excitatory intracortical synaptic inputs.
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