Attenuation of inhibitory synaptic transmission by glial dysfunction in rat thalamus
Article first published online: 12 AUG 2011
Copyright © 2011 Wiley-Liss, Inc.
Volume 65, Issue 12, pages 1298–1308, December 2011
How to Cite
Yang, S. and Cox, C. L. (2011), Attenuation of inhibitory synaptic transmission by glial dysfunction in rat thalamus. Synapse, 65: 1298–1308. doi: 10.1002/syn.20964
- Issue published online: 11 OCT 2011
- Article first published online: 12 AUG 2011
- Accepted manuscript online: 7 JUN 2011 10:43AM EST
- Manuscript Accepted: 24 MAY 2011
- Manuscript Received: 31 JAN 2011
- National Institutes of Health. Grant Number: EY014024
- thalamic reticular nucleus
The thalamus serves as the obligatory gateway to the neocortex for sensory processing, and also serves as a pathway for corticocortical communication. In addition, the reciprocal synaptic connectivity between the thalamic reticular nucleus (TRN) and adjacent thalamic relay nuclei generates rhythmic activities similar to that observed during different arousal states and certain neurological conditions such as absence epilepsy. Epileptiform activity can arise from a variety of neural mechanisms, but in addition glia are thought to have an important role in such activities as well. Glia serve a central role in glutamine synthesis, a precursor for glutamate or GABA in nerve terminals. While alterations in glutamine shuttling from glia to neurons can influence GABA and glutamate neurotransmission; the consequences of such action on synaptic transmission and subsequent network activities within thalamic circuits is less understood. We investigated the consequences of altering glutamine transport on inhibitory transmission and intrathalamic activities using the in vitro thalamic slice preparation. Disruption of the glutamine shuttling by the neuronal glutamine transporter (system A transporter) antagonist, α-(methylamino)isobutyric acid (MeAIB), or the selective gliotoxic drug, fluorocitric acid (Fc) dramatically decreased intrathalamic rhythmic activities. At the single cell level, MeAIB and Fc significantly attenuated electrically evoked inhibitory postsynaptic currents (eIPSCs) in thalamic relay neurons; however, miniature IPSCs were unaffected. These data indicate that glutamate-glutamine shuttle is critical for sustaining thalamic synaptic transmission, and thereby alterations in this shuttle can influence intrathalamic rhythmic activities associated with absence epilepsy. Synapse, 2011. © 2011 Wiley-Liss, Inc.