Neurophysiology: Keeping in synch in the LGN
Activation of a subtype of mGluR1a in the thalamus drives the generation of  - and  -rhythms in vivo.
A study by Hughes et al., published in Neuron, provides strong new evidence that activation of a subtype of metabotropic glutamate receptor, mGluR1a, in the thalamus drives the generation of - and -rhythms in vivo. These rhythms occur during wakefulness and early sleep, respectively, and the new study highlights the importance of mGluR1a and gap junctions in the thalamus for regulating rhythmic activity.
Electroencephalographic (EEG) recordings in humans show -rhythms (oscillations in the 8–13 Hz range) during relaxed wakefulness, particularly over the occipital cortex. When subjects become drowsy, the rhythms are replaced by activity in the range (2–7 Hz). To investigate previous suggestions that these cortical rhythms are driven by activity in the thalamus, Hughes et al. recorded from slices of the lateral geniculate nucleus (LGN) — the part of the thalamus that relays visual information to the cortex.
Rhythmic activity that resembled - and -rhythms was generated in the LGN when the authors applied mGluR1a agonists. Higher concentrations produced -like oscillations, and lower concentrations gave rise to -rhythms. Single-cell or local field potential recordings of the oscillations showed marked similarities to recordings that were made in vivo from the cat LGN during wakefulness or early sleep.
To test whether mGluR1a receptors are important for generating these rhythms in vivo, the authors treated cats with the mGluR1a-specific antagonist LY367385. This treatment rapidly suppressed -rhythm activity in the cat LGN and in EEG recordings over the occipital cortex, and also induced sleepiness in the animals.
What mechanisms are involved in the generation of - and -rhythms in the LGN? Intracellular recordings from thalamocortical neurons in LGN slices showed that treatment with an mGluR1 agonist caused a distinctive form of burst firing, with spontaneous, high-threshold bursts of spikes at 2–13 Hz. The bursts were very similar to those seen in extracellular recordings of - and -activity. They occurred at depolarized membrane potentials and seem to depend on Ni2+-sensitive Ca2+ channels.
When investigating how the rhythmic activity is synchronized between cells in the LGN, the authors discovered that blockers of chemical synaptic transmission did not prevent synchronization. However, blockers of gap junction transmission did, indicating that gap junctions are responsible for synchronized firing in the LGN. In support of this idea, a putative opener of gap junctions, trimethylamine, enhanced - and -oscillations.
When action potentials are transmitted through gap junctions in the thalamus, they give rise to 'spikelets'. The authors recorded bursts of these spikelets, which they term 'burstlets', corresponding to high-threshold bursts transmitted through gap junctions between thalamocortical neurons. These burstlets showed a number of properties that were identical to those of the high-threshold bursts.
Although these results provide compelling evidence that mGluR1 activation in the LGN produces rhythmic activity that is synchronized through gap junctions and that might drive - and -rhythms in the cortex, many questions remain to be investigated. Other areas of the brain are likely to be important for - and -rhythms in vivo. It will be essential to investigate how these areas and circuits interact to generate and sustain rhythmic activity under different conditions.
Rachel Jones
References
- Hughes, S. W. et al. Synchronized oscillations at and frequencies in the lateral geniculate nucleus. Neuron 42, 253–268 (2004) | Article | PubMed |
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