New rodent study shows how specific glial cells play a crucial role in spatial learning and memory

There are two fundamentally different cell types in the brain; neurons and glial cells. The latter, for example, insulate the ‘wiring’ of nerve cells or guarantee optimal working conditions for them.

A new study led by the University of Bonn has now discovered another function in rodents; the results suggest that a certain type of glial cell plays an important role in spatial learning.

We might come across a gnarled tree, with a babbling brook nearby flowing through a fragrant wildflower meadow and we will store this combination of features. When we then encounter the interplay of tree, brook, and wildflower meadow another time, our brain recognises it; we remember having been there before.

This is made possible by mechanisms such as the so-called dendritic integration of synaptic activity.

Professor Dr Christian Henneberger, from the Institute of Cellular Neuroscience at the University Hospital Bonn, said: “We were able to show that the so-called astroglial cells or astrocytes play an essential role in this integration. They regulate how sensitive neurons are to a specific combination of features.”

In the study, the researchers took a close look at neurons in the hippocampus of rodents. The hippocampus is a region in the brain that plays a central role in memory processes. This is especially true for spatial memory.

Henneberger, who is also a member of the Collaborative Research Center 1089 – where the research project was based – and the Transdisciplinary Research Area ‘Life & Health’ at the University of Bonn, added: “In the hippocampus, there are neurons that specialise in just that – place cells.”

There are about one million of these place cells in the mouse hippocampus alone. Each responds to a specific combination of environmental characteristics.

Place cells have long extensions; the dendrites. These are branched like the crown of a tree and dotted with numerous contact points. Information that our senses convey to us about a location arrives here. These contacts are called synapses.

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cell body

Dr Kirsten Bohmbach, who performed most of the experiments in the study, said: “When signals arrive at many neighbouring synapses at the same time, a strong voltage pulse occurs in the dendrite – a so-called dendritic spike.

“This process is what we call ‘dendritic integration’ – the spike only occurs when a sufficient number of synapses are active at the same time. Such spikes travel toward the cell body, where they can trigger another voltage pulse – an action potential.”

Place cells generate action potentials at regular intervals. The speed at which they do this can vary widely.

However, when mice orient themselves in a new environment, their place cells always oscillate in a special rhythm – they then generate five to ten voltage pulses per second. This rhythm causes the nerve cells to release certain messenger substances.

astrocytes

And this is where astrocytes come in; they have sensors to which these messenger substances dock, and in turn release a substance called D-serine.

Bohmbach explained: “The D-serine then migrates to the dendrites of the place cells. There, it ensures that the dendritic spikes can develop more easily and are also much stronger.”

When mice are in orientation mode, this makes it easier for them to store and recognise new locations.

Henneberger said: “If we inhibit the assistance provided by astrocytes in mice, they are less likely to recognise familiar places.”

However, this does not apply to locations that are particularly relevant – for example, if they pose a potential danger, which continue to be avoided by the animals.

He added: “The mechanism we discovered therefore controls the threshold at which location information is stored or recognised.”

The results provide a new insight into how memory works and is controlled. In the medium term, they may also help to answer the question of how certain forms of memory disorders develop.

The results are published in Nature Communications.

Image: Astrocytes (yellow) detect when the mouse is spatially oriented and then increase the probability of dendritic spikes by signalling molecules. © Kirsten Bohmbach/ University Hospital Bonn.