Abstract
Thalamus and cortex represent a highly integrated processing unit that elaborates sensory representations. Interposed between cortex and thalamus, the nucleus Reticularis thalami (nRt) receives strong cortical glutamatergic input and mediates top-down inhibitory feedback to thalamus. Despite growing appreciation that the nRt is integral for thalamocortical functions from sleep to attentional wakefulness, we still face considerable gaps in the synaptic bases for cortico-nRt communication and plastic regulation. Here, we examined modulation of nRt excitability by cortical synaptic drive in Ntsr1-Cre x ChR2tg/+ mice expressing Channelrhodopsin2 in layer 6 corticothalamic cells. We found that cortico-nRt synapses express a major portion of NMDA receptors containing the GluN2C subunit (GluN2C-NMDARs). Upon repetitive photoactivation (10 Hz trains), GluN2C-NMDARs induced a long-term increase in nRt excitability involving a potentiated recruitment of T-type Ca2+ channels. In anaesthetized mice, analogous stimulation of cortical afferents onto nRt produced long-lasting changes in cortical local field potentials (LFPs), with delta oscillations being augmented at the expense of slow oscillations. This shift in LFP spectral composition was sensitive to NMDAR blockade in the nRt. Our data reveal a novel mechanism involving plastic modification of synaptically recruited T-type Ca2+ channels and nRt bursting and indicate a critical role for GluN2C-NMDARs in thalamocortical rhythmogenesis.
Highlights
Much advancement has recently been achieved in the conceptual understanding of the nucleus Reticularis thalami
We found that photoactivated corticoreticular NMDAR currents are largely mediated by GluN2C-containing receptors (GluN2C-NMDARs), a subtype reported to be expressed in nucleus Reticularis thalami (nRt) cells and associated with pathophysiological thalamic rhythmogenesis[35,36,37,38]
We ruled out non-specific effects of NMDAR blockade on glutamate release at cortical inputs, which might act as a confounding factor when measuring postsynaptic NMDA-excitatory postsynaptic currents (EPSCs) inhibition
Summary
Much advancement has recently been achieved in the conceptual understanding of the nucleus Reticularis thalami (nRt). Synchronous and repetitive activation of cortical inputs may induce sufficient NMDAR activation and trigger plastic regulations of the corticoreticular feedback that outlast the already described short-term dynamics. Such activity-dependent long-lasting modulation is likely to be central for keeping up with behavioral demands of arousal states. We set out to define mechanisms of corticoreticular plasticity using optogenetic stimulation of cortical afferents onto sensory sectors of nRt in Ntsr1-Cre x ChR2tg/+ mice, that express the light-gated ion channel Channelrhodopsin[2] (ChR2) selectively in corticothalamic layer 6 cells[33,34]. The modulation of cortical rhythms was long-lasting and sensitive to local NMDAR blockade in the nRt
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