Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Prefrontal–Thalamo–Hippocampal circuit for Goal-Directed Navigation


Nature  522, 50–55 (04 June 2015)

A prefrontal–thalamo–hippocampal circuit for goal-directed spatial navigation

Hiroshi T. Ito,

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Olav Kyrres gate 9, MTFS, 7491 Trondheim, Norway


Spatial navigation requires information about the relationship between current and future positions. The activity of hippocampal neurons appears to reflect such a relationship, representing not only instantaneous position but also the path towards a goal location. However, how the hippocampus obtains information about goal direction is poorly understood. Here we report a prefrontal–thalamic neural circuit that is required for hippocampal representation of routes or trajectories through the environment. Trajectory-dependent firing was observed in medial prefrontal cortex, the nucleus reuniens of the thalamus, and the CA1 region of the hippocampus in rats. Lesioning or optogenetic silencing of the nucleus reuniens substantially reduced trajectory-dependent CA1 firing. Trajectory-dependent activity was almost absent in CA3, which does not receive nucleus reuniens input. The data suggest that projections from medial prefrontal cortex, via the nucleus reuniens, are crucial for representation of the future path during goal-directed behaviour and point to the thalamus as a key node in networks for long-range communication between cortical regions involved in navigation.

Hippocampal place cells are part of an allocentric representation of local space that allows animals to navigate to desired locations. Place cells provide accurate information about current location, but it has remained unclear how the place-cell map is used for animals to navigate from their current position to a goal position elsewhere in the environment. To implement goal-directed navigation, previous studies have proposed the need for a separate representation of future positions that is somehow brought together with the representation of current location to point the network to the goal. Such pointers may be expressed in the activity of hippocampal place cells. When rats are engaged in a T-maze-based alternation task, in which they take left or right trajectories on alternating laps, place cells with fields on the stem of the maze fire at different rates on left- and right-turn trajectories, without changes in the position of the firing field. The dependence on trajectory has both retrospective and prospective components, reflecting both where the animal comes from and where it is going. However, as the animal approaches the decision point at the junction of the maze, the representation becomes more forward-oriented, often with trajectories to upcoming locations embedded into the representation, in addition to mere changes in firing rate.

The source of trajectory information in place cells has not been identified. Here we used a continuous version of the T-maze alternation task6 to determine how information about succeeding choices is introduced in hippocampal place-cell activity. We hypothesized that the selection of future trajectories depends on a wider circuit including not only the hippocampus but also structures involved in the evaluation and selection of actions, such as the prefrontal cortex. Neurons in medial prefrontal cortex (mPFC) do not project directly to the hippocampus but the midline thalamic nucleus reuniens (NR), which has reciprocal anatomical connections with the mPFC, may serve as a functional bridge to the hippocampal region, since NR has strong terminal fields in the CA1 subfield. To address this possibility, we recorded and manipulated activity at various nodes of the prefrontal–reuniens–CA1 circuit and determined whether this circuit is necessary for place cells to represent upcoming trajectories.

Trajectory-dependent firing is stronger in CA1 than CA3.

We first asked whether NR is the source of trajectory information in CA1. If it is, we should observe a difference in trajectory-dependent firing between CA1 and CA3, because NR has major excitatory projections to CA1 but not CA3. We thus recorded place cells in rat CA1 and CA3 in a continuous alternation task on a modified T-maze. A total of 363 CA1 cells and 180 CA3 cells exhibited location-specific complex spiking (12 and 5 rats, respectively). Within this sample, 98 CA1 cells and 34 CA3 cells had place fields on the central stem. All subsequent analysis of these cells was restricted to parts of the stem where there was no significant difference in the animal’s head direction, lateral position, or running speed between left-turn and right-turn trajectories.

NR receives strong projections from mPFC, suggesting that it serves as a relay between mPFC and CA1.

When animals plan a route to a desired location, they must estimate how spatial position is changed following particular movements. Our study points to mPFC, NR and CA1 as part of the neural circuit for representation of goal-directed routes or trajectories. The data suggest that while distinct sets of CA1 cells are activated at each spatial position, the distribution of firing rates among these cells collectively represents the animal’s intended direction of movement, and that this information is carried from the prefrontal cortex to CA1 through the midline thalamic NR. At each node of this loop, cells have firing rates that reflect the animal’s subsequent trajectory. Disrupting the loop at the level of NR substantially reduces the trajectory dependence of the representation in CA1. CA3 cells, which do not receive direct input from NR, exhibit little trajectory-dependent activity, despite the strong remapping seen in this subfield during changes in the sensory environment. Taken together, the results point to the mPFC–NR–CA1 circuit, and possibly indirect projections from mPFC and NR via the entorhinal cortex, as a key element of the circuit for map-based route planning. The data provide functional support for the idea that communication between cortical regions is mediated not only by direct connections but also through the thalamus.

We have shown that trajectory-dependent firing exists in multiple brain circuits. Trajectory information from mPFC may reach systems involved in motor planning and decision making directly, without passing through the hippocampus. This may be sufficient to enable choice behaviour in a simple alternation task. The copy of the trajectory signal that is sent to the hippocampus, via the NR, may become critical only when navigational decisions require combinatorial representation of trajectory and location. Such combinatorial representations were observed only in CA1. Nonlinear combination of information modalities has been described in individual neurons in a number of brain systems and is thought to increase the discrimination capacity of downstream neurons during encoding of high-dimensional information. In the hippocampus, combinatorial coding in trajectory-dependent place cells may form the basis for complex navigational operations in efferent regions such as the subiculum or the entorhinal cortex. High-dimensional representations in trajectory-dependent place cells may be necessary for networks in these regions to classify complex position–trajectory combinations.

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