Researchers Track Individual Neurons during Learning and Memory Recall

Neurobiologists at the Research Institute of Molecular Pathology (IMP) in Vienna were able to track single neurons in the brain of mice over extended time periods. Advanced imaging techniques allowed them to pinpoint the processes during memory formation and recall.

Oscar Wilde wrote that “Memory is the diary that we all carry about with us”.

But memory impacts us more far than a diary does. Indeed, most of our behavior, and so our personality, is shaped by previous experience.

That is why the capability to store the memory of these experiences and the ability to retrieve the information at will is considered one of the most basic and important functions of the brain.

The currently agreed on model in neuroscience proposes that memory is stored as long-lasting anatomical changes in synapses, the specialized structures by which nerve cells connect and signal to each other.

In Vivo Two-photon Imaging

At the IMP in Vienna, Simon Rumpel and Kaja Moczulska used mice to study the effects of learning and memorizing on the architecture of synapses.

They used an advanced microscopic technique called in vivo two-photon imaging that allows the analysis of structures as small as a thousandth of a millimetre in the living brain.

With this imaging technology, the neurobiologists tracked individual neurons over the course of several weeks and analysed them. They focussed their attention on the dendritic spines that decorate the neuronal processes and correspond to excitatory synapses.

The analyses were combined with behavioral experiments in which the animals underwent classic auditory conditioning.

New Synaptic Auditory Connections

The results showed that the learning experience triggered the formation of new synaptic connections in the auditory cortex.

Several of these new structures persisted over time, suggesting a long-lasting trace of memory and confirming an important prediction of the current model.

It was not just the changes during memory formation that the researchers were interested in. They also investigated the act of remembering.

Earlier studies had shown that memory recall is associated with molecular processes similar to the initial formation of memory. These similarities have been suggested to reflect remodelling of memory traces during recall.

To test their hypothesis, previously trained mice were exposed to the auditory cue a week after conditioning while tracking dendritic spines in the auditory cortex. Results showed that even though some molecular processes indeed resembled those during memory formation, the anatomical structure of the synapses did not change.

The findings suggest that memory retrieval does not lead to a modification of the memory trace per se. Instead, the molecular processes triggered by memory formation and recall could reflect the stabilization of previously altered or recently retrieved synaptic connections.

The chief goal of revealing the processes during memory formation and recall is to increase our basic knowledge of the brain. Insights gained from these studies might, however, also help us to understand diseases of the nervous system that affect memory.

In the future they may also provide the basis for treatments offering relief to traumatized patients.

Original Study:

Dynamics of dendritic spines in the mouse auditory cortex during memory formation and memory recall
Kaja Ewa Moczulska, Juliane Tinter-Thiede, Manuel Peter, Lyubov Ushakova, Tanja Wernle,Brice Bathellier, and Simon Rumpel
PNAS 2013 ; published ahead of print October 22, 2013, doi:10.1073/pnas.1312508110

Image: Cross section of the auditory cortex of a transgenic mouse. A single neuron is highlighted by green fluorescent protein. Dendritic spines that are corresponding to excitatory synapses are decorating the neuronal processes. Counterstaining for synaptic marker proteins ErbB4 (cyan) and Synapsin1 (magenta). Copyright: IMP