Spatial navigation is a fundamental ability for animals to survive in a geometric space. A prominent feature of rats is their ability to create an internal metric space, or a map, in their brain. While place cells in the hippocampus are considered key elements of the spatial...
Spatial navigation is a fundamental ability for animals to survive in a geometric space. A prominent feature of rats is their ability to create an internal metric space, or a map, in their brain. While place cells in the hippocampus are considered key elements of the spatial representation system, the activity of these cells primarily depends on the animal’s instantaneous position; thus it is not clear how the brain computes an estimate of future positions, necessary for route planning. Although several ideas have been proposed to extract future representations from place cells, how such information is generated in the hippocampus or is used in downstream brain structures is still largely unknown. The objective of this project is to clarify the roles of the hippocampus in the larger context of brain circuits for route planning. A growing body of evidence indicates key roles for the medial prefrontal cortex (mPFC) and the retrosplenial cortex (RSC) in navigation. We hypothesize that RSC, downstream of hippocampal area CA1, may represent the animal’s future position by making use of information from place cells about positions and movements. The future positions may then be evaluated in mPFC, a downstream target of RSC and CA1, which potentially represents the spatial proximity to the goal. In this project we will clarify the key circuit dynamics during route decisions among these structures together with the hippocampus. As route planning requires information about positional relationships in the environment, we will also investigate a role for brief trajectory sequences generated by place cells, or replay, for transferring such information from the hippocampus to RSC. Simultaneous high-density recordings from multiple regions as well as optogenetic silencing of specific projections are all available in freely behaving rats, and extensive use of computational methods will help decipher the codes in navigation circuits. The studies will provide key insights into how internal models in the brain influence cognition and behaviour, which may lead to the understanding of mental states with improper internal models as observed in patients of psychiatric disorders.
Our primarily aim during this first reporting period was to establish necessary techniques and methods to proceed each Work Package, which includes (i) establishment of behavioral tasks (ii) analysis of behavioral data during manipulation of the activity of neurons (iii) optimization of recording and imaging techniques.
Because our projects hugely rely on the newly designed behavioral tasks, our first work is to design and build behavioral mazes with the help of the mechanical workshop in our institute. We successfully built 3 different mazes proposed in the Work Package 1-3, which can be operated automatically by detecting the animal’s lick and delivering water on the wells. We then worked to establish a training protocol for each behavioral task, so that rats would behave on the mazes in an expected manner.
After the establishment of behavioral task, we first examined the impact of the nucleus reuniens inactivation for a navigation task (Work Package 1). We found that the nucleus inactivation did not impair the navigation ability when the optimal trajectory to the goal is simply a straight path. However, when the additional wall was introduced on the maze, the optimal path was not necessarily a straight path, and the animal was required to plan a trajectory that avoided the wall with the shortest distance. Here, we found that the animal with nucleus reuniens inactivation exhibited a deficit in navigation; the animal exhibited apparent confusion, wandering back and forth to search for the goal.
Overall our main result in this reporting period is that the nucleus reuniens is likely a key structure for route planning during navigation. Because this is the first study that identified a key brain area for route planning, we will further investigate how the animal can plan possible route candidates and decide an optimal one among them, by analyzing the activity of neurons in this brain area.
We introduced a miniature microscope by Inscopix.
After the optimization of the lens implantation, we successfully implemented the calcium imaging of neurons in the retrosplenical cortex in anesthetized rats. We will further optimize this technique for behaving rats.
More info: https://brain.mpg.de/institute/external-funding.html.