Figure 5. The role of the SUBdd and SUBdv in visuospatial integration and navigation.

(a) Double coinjection experiments targeted to the SUBdd and SUBdv (SW160909–04A) reveal similar topographically-organized anterogradely labeled projections including but not limited to the fornix (middle top), RSPv (right top), and ENT (bottom right). In the hippocampus, SUBdd retrograde labeling was distributed in the CA1d, whereas SUBdv retrograde labeling was distributed adjacent within the CA1i (bottom left, highly comparable to HGEA CA1d/CA1i boundary). Both SUBdd and SUBdv project to the POST, PRE, and PAR, but have reciprocal, complementary connectivity patterns. SUBdd projects to rostral POST and caudal PAR while SUBdv projects to rostral PAR and caudal POST (caudal section shown in bottom right). Within the ENT cortex, SUBdd and SUBdv receive input from the lateral and intermediate bands, respectively. Anterograde and retrograde coinjection into the RSPv reveals retrograde labeling in SUBdd and SUBdv layer 1 while anterogradely-labeled RSPv fibers primarily target the dorsal and ventral ends of layer 4. (b) Anterograde and retrograde coinjections into the SUBdd (SW111219–03A) and SUBdv (SW151028–03A) produces labeling pattern distributions within the LD thalamus that are highly similar to retrograde labeling patterns from the POST vs. PRE/PAR (SW140415–01A, outlined by dashed white lines). Double coinjections targeted to the medial vs. lateral part of the LD thalamus produced retrograde labeling within SUBdd and SUBdv layer 4 with laminar specific anterogradely labeled projections to the POST/PRE/PAR. (c) Organization of thalamic-projecting neurons. MM-projecting layer 1 neurons are distinct from RE/AMd-projecting layer 4 neurons within SUBdv (SW140625–02A). Within the bulbs of layer 4, AD-projecting neurons (similar to LD- and AV-projecting neurons) are distributed more superficial compared to RE-, PVT-, and PT-projecting neurons (SW160808–03A). At the caudal end of the subiculum, the AV-projecting layer 4 neurons in the dorsal and ventral bulbs join to become continuous along the medial part of the subiculum (SW140805–02A). Injection of G-deleted rabies virus into the AV thalamus (SW150707–01A) retrogradely labels AV-projecting layer 4 neuron cell bodies, axons, and dendrites. AV-projecting neurons at ARA 96 send their axons into the alveus while their thick dendritic shafts extend rostrally through the SUB at ARA 95 to bifurcate into thin dendritic branches in the superficial molecular layer at ARA 93 and avoid PHAL-labeled ENT axon fibers within the deeper molecular layer. Top right panel is magnified from red rectangle area in bottom left panel. (d) Comparison of multiple tracers reveals SUBdd and SUBdv projection cell types. In SW140805–02A, AV- and RE/AMd neurons were found to be relatively distinct projection neuron cell types within layer 4. Note, anterogradely-labeled AV fibers also terminate specifically in the dorsal and ventral bulbs. In contrast, almost all RSPv-projecting neurons were a subset of MM-projecting neurons in layer 1 (SW160721–01A). While RSPv-projecting SUB neurons are located in layer 1, anterogradely-labeled fibers from the RSPv predominantly terminate in the layer 4 dorsal and ventral bulb regions (SW110614–02A). Finally, case SW140625–01A contains four retrograde tracer injections into the RE/AMd, AV, MM, and LM that provides a comprehensive picture of projection cell types in the SUBdd and SUBdv at ARA level 95 that is remarkably similar to the HGEA. LM-projecting neurons are located primarily in PRE layer 3, MM-projecting neurons are located primarily within layer 1, and RE/AMD and AV-projecting neurons are located primarily within layer 4. (e) Wiring schematic diagram of SUBdd and SUBdv network connections with brain regions that contribute to visuospatial behavior (see Discussion). For the number of tracer experiments and cross-validated results, see the Supplementary Methods.