Deciphering the spatial representation of connected environments – ConnecSpace

Navigation is a critical ability for mammals. Over the past decades, numerous studies have revealed a network of brain areas containing space coding neurons, including hippocampal place cells, medial entorhinal grid cells, retrosplenial and anterothalamic head direction cells. The properties of these neurons have been almost exclusively described in rats moving in simple open fields, in which they are trained to search for food pellets randomly scattered on the floor. The natural environment is more complex: it is made of connected spaces between which we continuously move. Recently, I discovered a new population of space coding neurons in the retrosplenial cortex, called bidirectional cells, whose activity can be observed only when an animal navigates between two connected rooms. The existence of these bidirectional cells suggests that the brain processes underlying spatial navigation in natural environments remain to be uncovered. Moreover, this breakthrough highlights the shortcomings of current models of space representation in explaining the neural bases of navigation in natural environments. The goal of this proposal is to decipher the functional and anatomical brain networks supporting navigation in ecological conditions. To do so, I will combine single cell recording in freely moving rats with optogenetic or pharmacogenetic neural inactivation in well-designed behavioural protocols. In particular, I will test the hypothesis that retrosplenial cells provide spatial information about the local and global reference frames required to navigate within and between connected rooms, respectively. I will then investigate the anatomical pathways responsible for these processes by focusing on the thalamo-retrosplenial networks. Finally, I will test whether the activity of entorhinal grid cells and hippocampal place cells, two important classes of neurons coding space, is influenced by retrosplenial inputs in rats exploring connected environments.
Altogether, these experiments will unravel for the first time how the brain constructs the representation of a global space in complex environments. This project is therefore a necessary step to build a more comprehensive model of ‘real life’ spatial navigation, which is indispensable to understand spatial dysfunctions typical of different human pathologies, such as Alzheimer Disease.