Higher order (HO) thalamic nuclei are characterized by receiving driver input from layer 5 (L5) of cortex and serve as a transthalamic route of corticocortical communication. These HO nuclei are also innervated by subcortical sources. In the posterior medial nucleus (POm), a somatosensory HO thalamic nucleus, excitatory glutamatergic inputs arise from L5 of sensorimotor cortices and the spinal trigeminal nucleus (SpV), while inhibitory GABAergic sources are the anterior pretectal nucleus (APn) and zona incerta (ZI). Here, we tested a key postulate of transthalamic pathway function: that their disynaptic nature allows information traversing them from L5 to be modulated or gated by other inputs. We used optogenetics in acute slices from mice (both sexes) to test individual POm relays for convergent innervation. We found that modulatory inputs from SpV intersect with drivers from L5 of somatosensory cortex. Further, GABAergic inputs from the APn converge with both L5 and SpV inputs. In contrast, we found minimal convergence between ZI and L5 or SpV—a surprise considering previous evidence that ZI blocks whisker-dependent activation of POm relays. Therefore, we sought alternative explanations for this discrepancy. First, we detected robust convergence in POm between the ZI (and APn) and superior colliculus, which is whisker responsive. Second, we discovered that ZI innervates the thalamic reticular nucleus with glutamatergic synapses, comprising an alternative feedforward inhibitory circuit to POm. These results substantiate several mechanisms by which transthalamic information is modulated or gated while enhancing the resolution of our understanding of POm function. Significance Statement Environmental information arrives in cortex via pathways relayed through thalamus. It is then further processed by at least two circuits: direct corticocortical connections and recently appreciated cortico-thalamo-cortical (transthalamic) circuits. But why have transthalamic pathways that parallel direct ones? Here, we provide evidence for a potential reason—information traversing transthalamic circuits can be modified by inputs that converge onto transthalamic relay cells. Indeed, we show that both excitatory modification and inhibitory gating of transthalamic signals, as well as signals to thalamus relayed from certain subcortical sources, occur on relay cells in the somatosensory thalamus. These findings set the stage for understanding how individual thalamic relays integrate bottom-up and top-down (i.e., corticothalamic) information to dynamically regulate interregional cortical communication.
Koster et al. (Fri,) studied this question.