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

It is now widely accepted that certain types of cognitive functions are intimately related to synchronized neuronal oscillations at both low (alpha/theta) (4-7/8-13 Hz) and high (beta/gamma) (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 alpha/theta frequencies. Interestingly, key differences exist between mGluR- and mAchR-induced bursting, with the former involving extensive dendritic Ca2+ electrogenesis and being mimicked by a non-specific block of K+ channels with Ba2+, 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 Ca2+-activated K+ channels in TC neurons can lead to fast rhythmic bursting (FRB) at approximately 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

Glutamate Uptake Triggers Transporter-Mediated GABA Release from Astrocytes

Background: Glutamate (Glu) and c-aminobutyric acid (GABA) transporters play important roles in regulating neuronal activity. Glu is removed from the extracellular space dominantly by glial transporters. In contrast, GABA is mainly taken up by neurons. However, the glial GABA transporter subtypes share their localization with the Glu transporters and their expression is confined to the same subpopulation of astrocytes, raising the possibility of cooperation between Glu and GABA transport processes. Methodology/Principal Findings: Here we used diverse biological models both in vitro and in vivo to explore the interplay between these processes. We found that removal of Glu by astrocytic transporters triggers an elevation in the extracellular level of GABA. This coupling between excitatory and inhibitory signaling was found to be independent of Glu receptor-mediated depolarization, external presence of Ca2+ and glutamate decarboxylase activity. It was abolished in the presence of non-transportable blockers of glial Glu or GABA transporters, suggesting that the concerted action of these transporters underlies the process. Conclusions/Significance: Our results suggest that activation of Glu transporters results in GABA release through reversal of glial GABA transporters. This transporter-mediated interplay represents a direct link between inhibitory and excitatory neurotransmission and may function as a negative feedback combating intense excitation in pathological conditions such as epilepsy or ischemia