Search bioRxiv⌕ Search

Biology subjects

Ito, H. T.

Publications and source records attributed to Ito, H. T..

5 recordsLinked to original sources

Independently tunable subcortical oscillators enable prefrontal control of cortical coupling

Oscillatory coherence between brain regions varies flexibly with behavioral demands, yet the circuit mechanism underlying this control remains unclear. Theta rhythm, which coordinates prefrontal-hippocampal activity, is classically attributed to a pacemaker in the medial septum (MS), with the supramammillary nucleus (SuM) as its modulator. Here we show that SuM instead operates as an independently tunable theta oscillator. In rats performing a spatial alternation task, SuM theta frequency decreased before the choice point while MS theta frequency remained stable, reducing the SuM-MS frequency mismatch in both population spiking and local field potentials. The size of this mismatch predicted theta-rhythm coordination between the medial prefrontal cortex (mPFC) and hippocampal CA1 in both the alternation task and open-field foraging. Inhibiting direct mPFC input to SuM abolished the behavior-dependent modulation of SuM frequency and disrupted mPFC-CA1 coupling. These findings place a subcortical theta oscillator under top-down prefrontal control and identify the SuM-MS frequency mismatch as a control variable for interregional coordination.

neuroscience↗

A multiplexed striatal architecture for generalized spatial goal progress

Flexible goal-directed behavior requires a generalized internal metric that tracks progress toward goals across locations, routes, and behavioral contexts. Although hippocampal-entorhinal cognitive maps encode detailed spatial representations, whether the brain constructs an abstract distance-to-goal state that generalizes across arbitrary start-goal combinations--a prerequisite for reinforcement learning over space--remains unknown. Here we show that the nucleus accumbens (NAc) computes such generalized spatial states. Using large-scale population recordings and causal perturbations in rats navigating toward dynamically changing goals, we find that NAc activity encodes a scale-invariant distance-to-goal signal, normalized by total journey length, across maze geometries and task rules. A decoder trained on this signal transfers to novel journeys, tracking physical path length rather than remaining time. This signal emerges selectively during memory-guided but not cue-guided navigation, dissociating spatial distance-to-goal coding from purely motivational or value representations. It persists during hippocampal and medial entorhinal cortex silencing but depends critically on dopaminergic input from the ventral tegmental area, which is necessary for accurate goal targeting. Beyond the current goal, NAc populations encode distances to previous goals within orthogonal subspaces, enabling parallel evaluation of counterfactual spatial states without interference. Consistent with this multiplexed architecture, reward omission reinstates search behavior toward former goals, whereas suppressing dopamine release in the NAc abolishes this memory-guided reinstatement. These findings establish the NAc as a substrate for generalized, multiplexed spatial state abstraction, revealing a striatal computation that bridges cognitive mapping and reinforcement learning to enable flexible goal-directed behavior in dynamic environments.

neuroscience↗

Locomotion-invariant prefrontal-thalamic goal states organize spatially aligned episode-specific hippocampal maps

Animals repeatedly traverse the same environment to pursue different goals, yet the hippocampus must preserve a stable spatial map while keeping individual episodes distinct. Here we show that, when animals navigate the same maze under different goal configurations, hippocampal CA1 segregates navigation episodes by encoding goal state along a population dimension orthogonal to the spatial coding subspace, rather than by reorganizing spatial representations themselves, allowing episode-specific maps to remain spatially aligned. This goal-state signal is supplied by a prefrontal-thalamic pathway, in which population activity in medial prefrontal cortex and nucleus reuniens forms persistent representations across locomotion and immobility and is reliably reinstated when previously experienced goal configurations recur. Silencing the nucleus reuniens selectively abolishes CA1 goal-state coding by disrupting goal-axis separation and goal-biased pre-navigation spike sequences while sparing spatial coding. Together, these findings identify a circuit- and population-level mechanism that enables episode-specific hippocampal representations to coexist within spatially consistent maps independent of locomotor state, linking internal goal states to navigation and planning.

neuroscience↗

The orbitofrontal cortex forms a context-generalized spatial schema that preserves topology and distance

Flexible and efficient navigation requires the brain to construct maps that are both topological, preserving the relationships between locations, and schematic, enabling generalization across environments. Although spatial maps in the hippocampus (HPC) and medial entorhinal cortex (MEC) have been extensively studied, they remap almost orthogonally across environments even during identical behaviors, raising the question of how animals maintain consistent navigation strategies across spatial contexts. Here, we identify a novel spatial map in the orbitofrontal cortex (OFC) that encodes navigational targets with distinct neural representations while preserving their topological order and relative distances by scaling to physical path lengths. Remarkably, OFC maps remained stable when animals performed the same navigation task across rooms and maze geometries, in stark contrast to the pronounced remapping observed in HPC and MEC. Moreover, OFC maps persisted after HPC or MEC lesions, demonstrating an independent spatial mapping system. These findings reveal a task-relevant topological schema in the OFC that uniquely supports flexible context-invariant navigation, expanding the brains spatial mapping repertoire beyond the hippocampal-entorhinal system.

neuroscience↗

Representation of Distance and Direction of Nearby Boundaries in Retrosplenial Cortex

Borders and edges are salient and behaviourally relevant features for navigating the environment. The brain forms dedicated neural representations of environmental boundaries, which are assumed to serve as a reference for spatial coding. Here we expand this border coding network to include the retrosplenial cortex (RSC) in which we identified neurons that increase their firing near all boundaries of an arena. RSC border cells specifically encode walls, but not objects, and maintain their tuning in the absence of direct sensory detection. Unlike border cells in the medial entorhinal cortex (MEC), RSC border cells are sensitive to the animals direction to nearby walls located contralateral to the recorded hemisphere. Pharmacogenetic inactivation of MEC led to a disruption of RSC border coding, but not vice versa, indicating network directionality. Together these data shed light on how information about distance and direction of boundaries is generated in the brain for guiding navigation behaviour.

neuroscience↗