GOAL-DIRECTED PLANNING IN DENTATE NETWORKS – DG-Goal

The hippocampal formation supports our sense of place through the presence of spatially-modulated firing of hippocampal place cells and entorhinal grid cells. We depend on this network for recognizing and remembering the environment. As such, this system supports one of the most fundamental brain function: our ability to navigate in the environment looking out for relevant locations. Theory of spatial navigation indicates that the current as well as the expected ending location are coded within the place system and that journeys between these relevant locations are planned through “mental travelling” or “prospective planning”. One likely neural mechanism underlying this prospective planning is the presence, when the animal is facing a complicated choice, of theta sequences, i.e. time-compressed, ensemble representations of possible future trajectories through the environment. However, the majority of studies on the place system are based on behaviors relatively remote from most of the spatial navigation occurring in real life. They often employed tasks with a large number of trials per session in which navigation can be automated after extensive training, switching from a place navigation (allocentric) to a response (egocentric) strategy. However, navigation often involves reaching a fixed goal location in a complex environment after only limited experience using an allocentric strategy. Building on this conceptual framework, our project aims at understanding how animals plan their journey in complex spatial reference memory tasks heavily relying on allocentric-based strategy and not permitting transition to egocentric-based navigation.
Our recent publication and preliminary results have revealed a highly specific learning-dependent recruitment of dentate networks, unveiled by an increase in theta-gamma coupling, at the vicinity of the target area. We hypothesized that this increased theta-gamma coupling, present only in navigational tasks involving allocentric strategies, might reflect a network signature of planning processes implicated in direct navigation toward the goal. Our preliminary data further indicate that this dentate signal likely originates from entorhinal cortex inputs. Based on these results, our project aims specifically at 1) determining if the increased theta-gamma coupling is associated with the presence of look-ahead theta sequences in the dentate gyrus, 2) demonstrating the functional importance of the entorhinal cortex in the emergence of these look-ahead theta sequences in the dentate gyrus, and 3) characterizing the dynamics of this coupling in the hippocampal formation across training.
To do so, we will perform in vivo electrophysiological recordings of individual dentate granule cells in mice during learning of the spatial reference memory task we recently developed (ATA task). We will assess whether increased theta-gamma coupling in dentate networks relates to the emergence of specific theta sequences looking ahead, from the current physical position of the animal, toward the goal (WP 1.1). Not only will we look at the local computation within dentate networks, but also at the effect of such dentate computation on downstream targets (WP 1.2). If increased theta-gamma coupling in the DG represents a network signature of a goal planning process, interfering with this planning using optogenetics should thus alter goal-reaching performance. Given our preliminary results suggest that the prominent dentate theta-gamma coupling might originate from entorhinal inputs, we will therefore test how the inhibition of this specific pathway (WP2.1) influences behavioral performance in the maze (WP 2.2) and the dentate planning process (WP2.3).
Our project will therefore bring new insight on how hippocampal networks participate to the process of goal-directed route planning during spatial navigation in complex environments