Laminar distribution of cortical projection neurons to the pulvinar: A comparative study in cats and mice

Abstract

The cortical processing of visual information is thought to follow a hierarchical framework. This framework of connections between visual areas is based on the laminar patterns of direct feedforward and feedback cortico-cortical projections. However, this view ignores the cortico-thalamo-cortical projections to the pulvinar nucleus in the thalamus, which provides an alternative transthalamic information transfer between cortical areas. It was proposed that corticothalamic (CT) pathways follow a similar hierarchical pattern as cortico-cortical connections. Two main types of CT projections have been recognized: drivers and modulators. Drivers originate mainly in Layer 5 whereas modulators are from Layer 6. Little is known about the laminar distribution of these projections to the pulvinar across visual cortical areas. Here, we analyzed the distribution of CT neurons projecting to the lateral posterior (LP) thalamus in two species: cats and mice. Injections of the retrograde tracer fragment B of cholera toxin (CTb) were performed in the LP. The morphology and cortical laminar distribution of CTb-labeled neurons was assessed. In cats, neurons were mostly found in Layer 6 except in Area 17, where they were mostly in Layer 5. In contrast, CT neurons in mice were mostly located in Layer 6 across all areas. Thus, our results demonstrate that CT projections in mice do not follow the same organization as cats suggesting that the transthalamic pathways play distinct roles in these species.

Distinct “driving” versus “modulatory” influences of different visual corticothalamic pathways

“…The mouse pulvinar receives cortical input from two excitatory cell types in V1: L6CTs and L5CTs (Figure 1A). Consistent with prior studies, 4,5,30,31 we confirmed that injections of a retrograde tracer (cholera toxin subunit B; CTB) into the pulvinar labeled CT neurons in V1 L6-primarily in the lower half of L6-and in L5, as well as in L6 and L5 of surrounding extrastriate cortical areas (Figure 1B). We also observed more prominent L5 labeling when using a self-complementing retrograde adeno-associated virus (scAAVretro) injected into the pulvinar to retrogradely express a fluorophore without infecting L6CTs (which is characteristic of AAVretro tropism; 37 Figure 1B).…”

“…These findings are consistent with reports that L6CTs do not inhibit (and can even excite) layer 5 60 and make it unlikely that intracortical effects of L6CT inactivation can explain the consequences (or lack thereof) of L6CT inactivation on the pulvinar. Another consideration is that many L6 projections to the rodent pulvinar come from extrastriate areas 4,5,30,31 (Figure 1B), which were not targeted by our injections. Our findings of fundamentally similar modulatory influences of V1 L6CTs in the dLGN and pulvinar (from our present inactivation and prior activation studies 41 ) would lead us to expect that the cumulative effect of L6CT inactivation across cortical areas on the pulvinar would be similar to what we observed in this study in the dLGN (which gets the majority of its L6CT input from V1 61,62 )-namely, suppressed spontaneous but not visual activity.…”

“…5,18,[71][72][73] These inhibitory pathways might underlie some of the excitatory effects we observed in the pulvinar with L5ET inactivation (Figures 4C and 4D). Meanwhile, the rodent pulvinar also receives excitatory L5 input not just from V1 but also from extrastriate areas 4,5,30,31 (Figure 1B). Based on our observations of some retinotopically aligned pulvinar units that were unaffected by L5ET inactivation (Figures 5F and S5E) or ablation (Figures S7H-S7J)-similar to what was observed in the cat following V1 cooling 24 -we predict that L5ETs in extrastriate areas may provide additional driving inputs.…”

“…41 As expected, axons were observed in both the pulvinar and dLGN following injection of a Cre-dependent AAV in V1 (Figure 1C). L6CTs in V1 that were retrogradely labeled from the pulvinar were largely restricted to lower L6 4,5,31 (Figures 1B and 1E) and were still a relative minority of all L6CT cells (34.71% in lower L6, 21.5% in all of L6; Figure 1E). Although these proportions are likely underestimates as a consequence of restricting our injections to avoid the dLGN, they indicate that not all V1 L6CTs project to the pulvinar.…”

“…This question is further complicated by the diversity of excitatory input sources to HO thalamic nuclei. The rodent pulvinar, for instance, receives additional L5 and L6 CT projections from extrastriate cortical areas, 4,5,30,31 as well as subcortical excitation from the superior colliculus (SC). 32 Notably, SC projections display a mix of driver and modulator characteristics 7 and have even been shown to drive activity in the caudomedial subdivision of the rodent pulvinar (cmPulv).…”