Periodic Reporting for period 1 - MentalTravel (Neural Circuits Enabling Navigational Simulations)
Periodo di rendicontazione: 2023-09-01 al 2026-02-28
One of the most notable features of the brain is the ability to simulate possible consequences of a behavioural choice that has not even been experienced in the real world. While this ability is likely fundamental for our intelligence and creativity, its neural circuit basis is largely unclear. To tackle this problem, we will focus on the rat’s ability of spatial navigation, finding an optimal path to a remote destination that is located outside the range of sensory perception. This ability is thought to be supported by the brain’s internal map that allows an animal to estimate its future position followed by planned movements. While the hippocampal formation has been the primary focus of research on the brain’s spatial map, it mainly tracks an animal’s position and its nearby trajectories. By contrast, the brain has another internal map in the orbitofrontal cortex (OFC) that points to an animal’s goal destination throughout navigation. Because this goal coding emerges autonomously in the network without relying on explicit external cues, it can be considered part of the brain’s inner reasoning process for future behaviours. Here we will explore how this internally-set goal can emerge in the OFC network through interactions with its associated regions – thalamus and neuromodulatory systems. We will then explore how this goal coding can be used to plan an optimal goal-directed path by avoiding known obstacles in the environment. Since this process likely requires the cooperation of two internal maps in OFC and the hippocampus, we will elucidate the underlying circuit mechanism that employs multiple map systems in parallel. We will take advantage of state-of-the-art experimental and analysis techniques to decipher neural codes for navigational simulations. The OFC and the hippocampus are the regions often affected by psychiatric disorders, and their role in inner reasoning may provide new insights into their pathophysiology.
During this reporting period, we achieved several key milestones in line with the original project plan. While some findings were anticipated, others were unexpected, collectively providing a deeper understanding of navigation circuits and the neural representation of navigational goals.
Below is a summary of the main accomplishments for each work package (WP).
WP1: A Value Map in the Ventral Striatum and Memory-Based Goal Decisions
We recorded neuronal activity in the nucleus accumbens (NAc) to examine how spatial values are represented in this region. While previous studies reported that NAc neurons encode valuable locations, we found that their activity precisely tracks the distance between the animal’s current position and its goal destination. Notably, this goal proximity coding extended beyond the current target to include previously visited goal locations. Behavioral experiments confirmed that this retrospective coding supports the animal’s ability to visit prior goals, suggesting that these neural signals reflect elements of goal memory. Our findings point to the NAc as a spatial metric system that complements the hippocampal formation, with a distinct role in encoding the distance to goal locations.
WP2: Prefrontal-Thalamic Inputs Drive Goal-Directed Replay Sequences in the Hippocampus
Building on the role of the orbitofrontal cortex (OFC) in goal representation, we found that silencing neurons in the nucleus reuniens (NR) disrupts hippocampal replay sequences directed toward upcoming goals. This highlights the importance of prefrontal-thalamic inputs in organizing prospective hippocampal activity during goal-directed navigation.
WP3: Spatial Representations in the OFC and Hippocampus
We compared spatial coding in the OFC and hippocampus during a navigation task. While the hippocampal map adapted to different environments, the OFC map maintained stable spatial representations across rooms as long as the task rule is consistent. These findings reveal distinct dynamics between the two systems and suggest a complementary interaction for flexible navigational planning.
Below is a summary of the main accomplishments for each work package (WP).
WP1: A Value Map in the Ventral Striatum and Memory-Based Goal Decisions
We recorded neuronal activity in the nucleus accumbens (NAc) to examine how spatial values are represented in this region. While previous studies reported that NAc neurons encode valuable locations, we found that their activity precisely tracks the distance between the animal’s current position and its goal destination. Notably, this goal proximity coding extended beyond the current target to include previously visited goal locations. Behavioral experiments confirmed that this retrospective coding supports the animal’s ability to visit prior goals, suggesting that these neural signals reflect elements of goal memory. Our findings point to the NAc as a spatial metric system that complements the hippocampal formation, with a distinct role in encoding the distance to goal locations.
WP2: Prefrontal-Thalamic Inputs Drive Goal-Directed Replay Sequences in the Hippocampus
Building on the role of the orbitofrontal cortex (OFC) in goal representation, we found that silencing neurons in the nucleus reuniens (NR) disrupts hippocampal replay sequences directed toward upcoming goals. This highlights the importance of prefrontal-thalamic inputs in organizing prospective hippocampal activity during goal-directed navigation.
WP3: Spatial Representations in the OFC and Hippocampus
We compared spatial coding in the OFC and hippocampus during a navigation task. While the hippocampal map adapted to different environments, the OFC map maintained stable spatial representations across rooms as long as the task rule is consistent. These findings reveal distinct dynamics between the two systems and suggest a complementary interaction for flexible navigational planning.