PT - JOURNAL ARTICLE AU - Richevaux, Louis AU - Lim, Dongkyun AU - Nassar, Mérie AU - Rodrigues, Léa Dias AU - Mauthe, Constanze AU - Cohen, Ivan AU - Sol-Foulon, Nathalie AU - Fricker, Desdemona TI - Projection-specific integration of convergent thalamic and retrosplenial signals in the presubicular head direction cortex AID - 10.1101/2023.03.16.533014 DP - 2023 Jan 01 TA - bioRxiv PG - 2023.03.16.533014 4099 - http://biorxiv.org/content/early/2023/10/02/2023.03.16.533014.short 4100 - http://biorxiv.org/content/early/2023/10/02/2023.03.16.533014.full AB - Head-direction (HD) signals function as the brain’s internal compass. They are organized as an attractor, and anchor to the environment via visual landmarks. Here we examine how thalamic HD signals and visual landmark information from the retrosplenial cortex combine in the presubiculum. We find that monosynaptic excitatory connections from anterior thalamic nucleus and from retrosplenial cortex converge on single layer 3 pyramidal neurons in the dorsal portion of mouse presubiculum. Independent dual wavelength photostimulation of these inputs in slices leads to action potential generation preferentially for near-coincident inputs, indicating that layer 3 neurons can transmit a visually matched HD signal to medial entorhinal cortex. Layer 4 neurons, which innervate the lateral mammillary nucleus, form a second step in the association of HD and landmark signals. They receive little direct input from thalamic and retrosplenial axons. We show that layer 4 cells are excited di-synaptically, transforming regular spiking activity into bursts of action potentials, and that their firing is enhanced by cholinergic agonists. Thus, a coherent sense of orientation involves projection specific translaminar processing in the presubiculum, where neuromodulation facilitates landmark updating of HD signals in the lateral mammillary nucleus.Competing Interest StatementThe authors have declared no competing interest.