Novel modes of rhythmic burst firing at cognitively-relevant frequencies in thalamocortical neurons

Abstract

It is now widely accepted that certain types of cognitive functions are intimately related to synchronized neuronal oscillations at both low (α/θ) (4–7/8–13 Hz) and high (β/γ) (18–35/30–70 Hz) frequencies. The thalamus is a key participant in many of these oscillations, yet the cellular mechanisms by which this participation occurs are poorly understood. Here we describe how, under appropriate conditions, thalamocortical (TC) neurons from different nuclei can exhibit a wide array of largely unrecognised intrinsic oscillatory activities at a range of cognitively-relevant frequencies. For example, both metabotropic glutamate receptor (mGluR) and muscarinic Ach receptor (mAchR) activation can cause rhythmic bursting at α/θ frequencies. Interestingly, key differences exist between mGluR- and mAchR-induced bursting, with the former involving extensive dendritic Ca 2+ electrogenesis and being mimicked by a non-specific block of K + channels with Ba 2+, whereas the latter appears to be more reliant on proximal Na + channels and a prominent spike afterdepolarization (ADP). This likely relates to the differential somatodendritic distribution of mGluRs and mAChRs and may have important functional consequences. We also show here that in similarity to some neocortical neurons, inhibiting large-conductance Ca 2+-activated K + channels in TC neurons can lead to fast rhythmic bursting (FRB) at ∼ 40 Hz. This activity also appears to rely on a Na + channel-dependent spike ADP and may occur in vivo during natural wakefulness. Taken together, these results show that TC neurons are considerably more flexible than generally thought and strongly endorse a role for the thalamus in promoting a range of cognitively-relevant brain rhythms.