Brain state and memory study finds readiness shifts in mice

A University of Tübingen team has reported that spontaneous shifts in brain state and memory readiness move together in mice, changing which hippocampal neurons are active even when animals are resting. The finding matters because it points to short periods when the brain may be more prepared to store a new experience, according to the researchers.

The study, led by Professor Andrea Burgalossi at the Institute of Neurobiology and the Werner Reichardt Center for Integrative Neuroscience, was published in Nature Communications. The team investigated why many daily experiences fade while others become lasting memories.

How does brain state affect memory formation?

The researchers studied mice and focused on the hippocampus, a brain region they described as essential for episodic memory, the memory of experienced events. The hippocampus in mammals, including mice and humans, contains place cells, neurons that represent experiences and environments in brain activity.

Dr. Eduardo Blanco-Hernandez of the University of Tübingen, a lead author of the study, said researchers can put mice in different environments and observe distinct sets of place cells becoming active. In the team’s interpretation, those cell patterns allow scientists to watch memory-related activity appear or return.

The team recorded the activity of memory-related neurons while also tracking the animals’ internal state. According to the study, mice that were not moving still shifted between more and less alert states.

Nicola Sartorato, a CIN researcher and study co-author, said pupil size can be used to estimate that internal state. The researchers used the same principle seen in people and mice: pupils widen when alertness or engagement rises.

The researchers found that these spontaneous alertness changes strongly affected which place cells were active at a given moment. Sartorato said a particular subset of place cells became more active when the animals grew more alert, suggesting that internal state can quickly alter the neural basis used for episodic memories.

The same shifts appeared in brain rhythms, according to the study. Theta oscillations, patterns of neural activity associated by researchers with memory encoding, became stronger or weaker depending on the animal’s internal state.

What did the researchers test next?

The team then examined whether these state changes marked times when the brain was more plastic. Burgalossi said plasticity is central to memory because it is the process through which the brain physically stores experiences by changing connections and activity patterns.

According to Burgalossi, this rapid adjustment is especially relevant for episodic memory because lived events may occur only once, without rehearsal. The researchers therefore tested whether internal-state fluctuations could signal moments when the hippocampus was more ready to change.

To test that idea, the team stimulated individual memory-related neurons during those states. The study reports that the stimulation produced new memory-like activity patterns, including new place-specific responses, which the researchers described as effectively creating new memory cells within the network.

Taken together, the authors said the findings show that the hippocampus is more dynamic than a static storage system and can enter brief windows when it is especially ready to rewire. Burgalossi said identifying such naturally plastic moments gives researchers a controlled way to study how memories are physically formed in the brain.

The paper is titled “Place and behavioral modulation of hippocampal neurons during immobility.” Its authors include Nicola Sartorato and colleagues, and it was published in Nature Communications.

This story draws on original reporting from Medical Xpress.