Prefrontal projections to the thalamic reticular nucleus form a unique circuit for attentional mechanisms.

The inhibitory thalamic reticular nucleus (TRN) intercepts and modulates all corticothalamic and thalamocortical communications. Previous studies showed that projections from sensory and motor cortices originate in layer VI and terminate as small boutons in central and caudal TRN. Here we show that prefrontal projections to TRN in rhesus monkeys have a different topographic organization and mode of termination. Prefrontal cortices projected mainly to the anterior TRN, at sites connected with the mediodorsal, ventral anterior, and anterior medial thalamic nuclei. However, projections from areas 46, 13, and 9 terminated widely in TRN and colocalized caudally with projections from temporal auditory, visual, and polymodal association cortices. Population analysis and serial EM reconstruction revealed two distinct classes of corticoreticular terminals synapsing with GABA/parvalbumin-positive dendritic shafts of TRN neurons. Most labeled boutons from prefrontal axons were small, but a second class of large boutons was also prominent. This is in contrast to the homogeneous small TRN terminations from sensory cortices noted previously and in the present study, which are thought to arise exclusively from layer VI. The two bouton types were often observed on the same axon, suggesting that both prefrontal layers V and VI could project to TRN. The dual mode of termination suggests a more complex role of prefrontal input in the functional regulation of TRN and gating of thalamic output back to the cortex. The targeting of sensory tiers of TRN by specific prefrontal areas may underlie attentional regulation for the selection of relevant sensory signals and suppression of distractors.