Synchronized Paroxysmal Activity in the Developing Thalamocortical Network Mediated by Corticothalamic Projections and “Silent” Synapses

Abstract

In mouse thalamocortical slices in vitro, the potassium channel blocker 4-AP and GABAA receptor antagonist bicuculline together induced spontaneous prolonged depolarizations in layer VI neurons from postnatal day 2 (P2), in ventroposterior nucleus neurons (VP) from P7, and in reticular nucleus neurons (RTN) from P8. Dual whole-cell recordings revealed that prolonged bursts were synchronized in layer VI, VP, and RTN. Bursts were present in cortex isolated from thalamus, but not in thalamus isolated from cortex, indicating that bursts originated in cortex and propagated to thalamus. Prolonged bursts were synchronized in layer VI when vertical cuts extended from pia mater through layers IV or V, but were no longer synchronized when cuts extended through layer VI and white matter. In voltage-clamp recordings before P10, burst conductance of all three neuronal populations was dominated by the NMDA receptor-mediated conductance, and therefore synapses were "silent". In cortex and RTN, after P10, bursts were associated with strong AMPA/kainate receptor-mediated conductances, and synapses had become "functional"; silent synapses persisted in a large proportion of VP cells after P10. Before P9, the NMDA receptor antagonist APV or the non-NMDA receptor antagonist CNQX blocked the prolonged bursts. After P9, CNQX continued to block the prolonged bursts, but APV merely shortened their duration. Thus, NMDA receptor-based silent synapses are essential for paroxysmal corticothalamic activity during early postnatal development, and connections between layer VI neurons are sufficient for horizontal cortical synchronization.

Corticofugal Gating of Auditory Information in the Thalamus: AnIn VivoIntracellular Recording Study

“…Although both the cortex and thalamus have an intrinsic capacity to generate oscillations of varied frequencies, the corticothalamic loop is an ideal oscillator (Destexhe et al, 1993;Steriade et al, 1993a,b;von Krosigk et al, 1993;Golshani and Jones, 1999;Bal et al, 2000;Steriade, 2001a). The spindle-like oscillatory inhibitory wave in the membrane potential in Figure 6 D might be caused by the recurrent inhibition of the corticothalamic loops.…”

Slow Oscillation in Non-Lemniscal Auditory Thalamus

“…The TRN neurons are supposedly involved in the tone-evoked oscillation (Cotillon et al, 2000) and in slow and spindlelike oscillations (Steriade et al, 1993b,c;Grenier et al, 1998;Golshani and Jones, 1999;Steriade, 2001a). In a slice experiment of GABA Areceptor ␤ 3 knock-out mice, Huntsman and colleagues (1999) found that the oscillatory synchrony had dramatically intensified, suggesting that the reticular nucleus is very much involved in the regulation of the oscillation.…”

“…The spindle and slow oscillations have been shown in neurons in the dorsal lateral geniculate body and in the ventroposterior nucleus of the thalamus, respectively, with slice preparation (von Krosigk et al, 1993;Golshani and Jones, 1999). Both the cortex and the thalamus have an intrinsic capacity to generate oscillations of different frequencies (Steriade et al, 1993e;Destexhe et al, 1993;Golshani and Jones, 1999;Bal et al, 2000), but the slow-wave oscillations in the EEG are more likely to involve the corticothalamocortical loop (Steriade et al, 1993a-d). Cortical feedback controls the thalamic oscillation via the thalamic reticular nucleus (TRN) (Huntsman et al, 1999;Bal et al, 2000;Blumenfeld and McCormick, 2000;Golshani et al, 2001).…”

The GABAergic reticular nucleus: A preferential target of corticothalamic projections

“…26 and 27. mediated by cortico-RE projections. The role of corticothalamic projections in the generation of SW seizures (19) is now confirmed in a recent series of in vitro studies showing that bursting at 3 Hz in thalamic neurons can no longer be evoked in the thalamus after removal of cortex (21,22) and that corticofugal volleys induce thalamic activity at 3-4 Hz (23,24). These results stand in contrast to the previous hypothesis that thalamic networks are primarily (or even alone) implicated in the genesis of SW seizures.…”