The hippocampus builds internal maps that enable navigation without visual landmarks through a process called path integration. Researchers discovered two complementary excitatory networks — PyrUp and PyrDown — that encode elapsed distance and mark journey starts, supported by SST and PV inhibitory neurons that stabilize and reset timing. Optogenetic silencing of SST or PV caused mice to misjudge time or distance without changing speed. These circuit motifs may shed light on disorientation in Alzheimer’s disease and suggest targets for intervention.
Two Neural Networks Let Animals Navigate in the Dark — Clues to Dementia Disorientation
Lead image: Rudmer Zwerver / Shutterstock
Animals can often know where they are headed before their eyes register a route: the brain builds internal maps that act like an internal GPS, independent of visible landmarks. This navigation strategy, called path integration, lets animals update their position continuously by tracking steps and turns, enabling movement through space even when sensory cues are absent.
Place Cells and Internal Maps
Certain hippocampal neurons, called place cells, become active at particular locations regardless of whether the animal can see its surroundings. Populations of these neurons produce firing patterns that represent elapsed time and distance during movement, helping the brain know where the animal is in space.
How the Study Was Done
Researchers at the Max Planck Florida Institute for Neuroscience recorded and manipulated hippocampal circuits in mice to separate internal navigation signals from external sensory cues. Mice were trained to run fixed distances along a landmark-free virtual linear track to receive a reward. Because the track lacked salient visual cues, the animals had to rely on internal estimates of distance and time. While mice ran the course, the team recorded activity across hundreds of neurons and used targeted light-based perturbations (optogenetic silencing) to transiently suppress specific inhibitory cell types.
Key Findings
Analysis revealed two distinct excitatory activity patterns in the hippocampus. One excitatory population, labeled PyrUp, fired strongly at movement onset and then faded, with each neuron declining at a slightly different rate. The staggered decay across PyrUp cells provides a graded signal the brain could use to estimate how far into a journey it is. A complementary population, PyrDown, showed the opposite pattern: activity dipped at movement onset and then ramped up, a pattern that appears to mark the start of a new run and helps the brain avoid confusing successive trips.
The team then used light to silence two types of inhibitory neurons: SST cells (somatostatin-expressing), which help stabilize internal timing signals, and PV cells (parvalbumin-expressing), which act like a reset mechanism. Suppressing SST or PV cells caused mice to misjudge distance or time even though their running speed did not change. Control experiments ruled out motor impairments, visual deficits, or altered reward expectation as alternate explanations.
Implications
If similar circuit dynamics exist in humans, these findings may help explain why people with Alzheimer’s disease and other dementias become disoriented even in familiar places. The identified excitatory (PyrUp/PyrDown) and inhibitory (SST/PV) circuit motifs point to specific mechanisms that could be targeted in future therapies aimed at restoring spatial orientation.
“In sensory-rich environments it is difficult to tell whether neurons respond to sensory cues or to the animal’s position,” said Yingxue Wang, co-author and neuroscientist at the Max Planck Florida Institute for Neuroscience. This study isolates internal timing and distance signals and shows how interacting excitatory and inhibitory networks support path integration.
Methods note: The experiments combined large-scale neuronal recordings with optogenetic perturbations and rigorous behavioral controls to dissociate internal navigation signals from confounding sensory or motor factors.
