Dendritic spines are ubiquitous morpho-functional elements of excitatory synaptic transmission and plasticity. Whether axo-spinous communication exists in the thalamus is presently unclear. Here we find that layer 5 (L5) corticothalamic terminals arising from frontal cortices selectively target thalamic spines with classical head and neck dimensions. The synapses of the L5 axo-spinous contacts were enriched in GluR1 subunit of AMPA receptor and their size correlated with their spine head volume. Synaptic stimulation of thalamic spines resulted in compartmentalized Ca2+ responses similar to that of hippocampal spines. Optogenetic activation of the frontal L5-thalamus pathway had strong impact on thalamic spiking even at high stimulation frequencies and could selectively recruit a subnetwork of thalamic cells in a behavioral state dependent manner. Optogenetic interference with the small L5-thalamic pathway perturbed motor learning. Our study reveals a hitherto unrecognized, effective top-down communication channel between the frontal cortex and thalamus that involves highly variable axo-spinous contacts

Corticothalamic pathways, responsible for the top-down control of the thalamus, have a canonical organization such that every cortical region sends output from both layer 6 (L6) and layer 5 (L5) to the thalamus. Here we demonstrate a qualitative, region-specific difference in the organization of mouse corticothalamic pathways. Specifically, L5 pyramidal cells of the frontal cortex, but not other cortical regions, establish monosynaptic connections with the inhibitory thalamic reticular nucleus (TRN). The frontal L5-TRN pathway parallels the L6-TRN projection but has distinct morphological and physiological features. The exact spike output of the L5-contacted TRN cells correlated with the level of cortical synchrony. Optogenetic perturbation of the L5-TRN connection disrupted the tight link between cortical and TRN activity. L5-driven TRN cells innervated thalamic nuclei involved in the control of frontal cortex activity. Our data show that frontal cortex functions require a highly specialized cortical control over intrathalamic inhibitory processes.

SummaryCorticothalamic pathways, responsible for the top-down control of the thalamus display a classical, canonical organization in that every cortical region sends dual, layer 6 (L6) and layer 5 (L5) output to the thalamus. Here we demonstrate a qualitative, region-specific difference in the organization of corticothalamic pathways. We show that L5 pyramidal cells of the frontal, but not other cortical regions establish monosynaptic connection with the inhibitory thalamic reticular nucleus (TRN). The frontal L5-TRN pathway paralleled the L6-TRN projection but displayed distinct morphological and physiological features. The exact spike output of the L5 contacted TRN cells correlated with the level of cortical synchrony. Optogenetic perturbation of the L5-TRN connection disrupted the tight link between cortical and TRN activity. L5-driven TRN cells innervated all thalamic nuclei involved in the control of frontal cortical activity. Our data show that frontal cortical functions require a highly specialized cortical control over intrathalamic inhibitory processes.