Using light to reprogramme the brain's GPS

November 06, 2020

Neuroscientists at UCL have used laser beams to "switch on" neurons in mice, providing new insight into the hidden workings of memory and showing how memories underpin the brain's inner GPS system.

The study, published in the journal Cell, explains how researchers harnessed an 'all-optical' approach using twin lasers to simultaneously read and write the activity of 'place cells' (a type of neuron) in mice, as they navigated a virtual reality environment.

Remarkably, by stimulating the place cells, scientists were able to reactivate (or retrieve) the memory of a location where the mice obtained a reward, which in turn "mentally teleported" the mice, causing them to act as if they were in the rewarded place.

This new research builds on the groundbreaking work of Professor John O'Keefe (UCL Cell & Developmental Biology), who won the Nobel Prize in 2014 for discovering place cells. These cells are found in a brain region called the hippocampus, and only become active when an animal enters a specific location in the environment.

Place cells are thought to represent a cognitive map of the environment - like an inner GPS - and retain location memory. The new UCL study is the first to show directly that place cell activity underlies the brain's ability to navigate.

The results provide a deeper understanding of how memories are stored, and the UCL scientists believe the findings could eventually help us develop new therapies for conditions such as dementia and Alzheimer's disease, which affect memory.

First author Dr Nick Robinson (UCL Wolfson Institute for Biomedical Research) said: "These results provide direct causal evidence that mice use the information represented by place cell activity to guide their behaviour. In other words, place cells really do tell the mouse where it is, and mice actually 'listen' to their place cells when they make decisions. This provides new insights about how memories are stored in the brain, as well as new tools for manipulating these memories to influence behaviour."

He added: "Disorders of memory - such as in dementia and Alzheimer's - represent a huge cost to society. This work may eventually lead to a better understanding of these diseases, as well as new targets for therapeutic intervention."

Senior author Professor Michael Hausser (UCL Wolfson Institute for Biomedical Research) said: "This study is a game-changer as it shows that we can use optical reading and writing of activity in specific neurons to manipulate memories, allowing us to better understand - and potentially improve - how neural circuit activity helps us to make decisions."

The experimental study explained

Researchers at UCL Wolfson Institute for Biomedical Research leveraged a powerful approach which combines two revolutionary technologies for using light to read and write electrical activity in the brain.

First, they engineered neurons to express genetically encoded calcium sensors, which allow cells to light up when they are active. Second, they expressed light-sensitive 'optogenetic' proteins in the same neurons, allowing them to activate specific cells with beams of laser light, targeted using digital holography (the same technology as used in a laser light show).

By combining these two techniques, the team could both record and manipulate activity in the same neurons in the brain of a mouse navigating in virtual reality.

The UCL scientists used this approach to perform targeted activation of place cells in the hippocampus in mice navigating to a specific location within the virtual world to collect a sugar water reward. They first optically recorded the activity of large numbers of hippocampal place cells, identifying those which were active specifically at the rewarded location and which could therefore form the basis of the memory for that location. They then used holographically targeted laser beams to activate these specific place cells in a different location in the virtual world.

Remarkably, place cell stimulation was sufficient to retrieve the memory of the rewarded location, leading the mouse to seek the reward at the new location. In other words, the stimulation of the neurons with light "mentally teleports" the animal, causing them to act as if they were in the rewarded place. This is the first demonstration of how the activation of place cells enables us to retrieve memories of our environment and helps us to navigate.
-end-
Funding for this study was provided by Wellcome, the Gatsby Charitable Foundation, the European Commission, the European Molecular Biology Organization, the Medical Research Council and the European Research Council.

Notes to Editors

For more information or to speak to the researchers, please contact Henry Killworth, UCL Media Relations. T: +44 (0) 7881 833274 E: h.killworth@ucl.ac.uk

Research paper, Nick Robinson, Michael Hausser et al, "Targeted Activation of Hippocampal Place Cells Drives Memory-Guided Spatial Behaviour" will be published in the journal Cell at 16:00 UK Time Friday 6 November 2020 / 11:00 US Eastern time.

The DOI for this paper will be: https://doi.org/10.1016/j.cell.2020.09.061

University College London

Related Neurons Articles from Brightsurf:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.

Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.

A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.

Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.

Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.

Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.

The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.

Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.

How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.

Read More: Neurons News and Neurons Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.