Dendritic integration of thalamic HD signals and retrosplenial input in presubicular neurons

The head direction (HD) system functions as the brain's compass system. HD signals are generated based on vestibular inputs that provide information on self-movement. They are combined with signals that permit orientation coding with respect to external landmarks. Lesion studies point to the Presubiculum as a strong candidate for the integration of HD and landmark signals, but the underlying cellular mechanisms remain to be clarified. Here we show that the presubiculum receives HD signals from the anterior thalamic nucleus (ATN) and visual landmark information from the retrosplenial cortex (RSC). We examined the functional convergence of these inputs in the Presubiculum using dual-wavelength optogenetic stimulations in ex vivo brain slices, while recording from layer III pyramidal neurons. Both ATN and RSC projections made mono-synaptic excitatory connections onto single layer III pyramidal cells, with putative synapses often located close to each other on a same basal dendrite, and more RSC than ATN synapses on the apical tuft. Following photoactivation of Chronos and Chrimson, expressed in ATN and RSC respectively, postsynaptic firing was preferentially induced for near-coincident activation, in a short time window of -2 to +5ms. EPSPs induced by ATN and RSC fibers summed in a supralinear fashion. NMDA receptor activation assisted depolarization towards a threshold for the activation of voltage-dependent processes that underly supralinear summation of ATN and RSC inputs. Our data provide initial insights into the integration of landmark and HD inputs in single layer III presubicular pyramidal cells, potentially including HD cells and also grid cells. Our results suggest that landmarks become associated to HD signals in the presubiculum, where coactive synapses engage dendritic nonlinearities, allowing for rapid updating of the HD attractor.