Berlin-based researchers highlight protein important for learning and memory

Humans continue to learn throughout their lives. The underlying process, which is referred to as synaptic plasticity, is the result of activity-dependent modifications of the connections between different nerve cells. Researchers from the Charité – Universitätsmedizin Berlin and Cluster of Excellence NeuroCure have identified a protein that appears to play a central role in mediating this synaptic plasticity. Results from this study have now been published in the journal eLife*.

Learning and memory are associated with modifications to the connections between different nerve cells. These connections, known as synapses, allow nerve cells (neurons) within a particular neuronal network to communicate in a precisely timed manner. One crucial remaining question was whether the resulting synchronized, rhythmic patterns of network activity – known as network oscillations – are capable of inducing synaptic plasticity. Neuroscience researchers from the Charité’s Institute of Neurophysiology and the NeuroCure Cluster of Excellence have now clarified this by investigating gamma-band network oscillations, which are associated with attention and memory processing.

A signal transmitted by an excitatory neuron increases the likelihood of a downstream nerve cell being activated. Inhibitory neurons reduce this likelihood. Prof. Tengis Gloveli, Head of the 'Cellular and Network Physiology' working group at the Institute of Neurophysiology, and colleagues were able to show that, within the hippocampus (a brain area central to learning and memory), gamma oscillations exert an overall enhancing effect on subsequent network activities and lead to synaptic plasticity. The researchers were able to identify a specific receptor protein – the metabotropic glutamate receptor 5 – as a key component for these plastic changes. Pharmacological blocking of this receptor prevented changes in network activity and synaptic plasticity. A further detailed analysis revealed that, in parallel to this facilitating network effect, the excitability of excitatory neurons was enhanced. In contrast to excitatory neurons, the excitability of two types of certain inhibitory interneurons featured opposing effects: interneurons promoting the emergence of gamma oscillations exhibited enhanced activation, while those whose activity interferes with gamma oscillations showed a reduced excitability. The highly specific, contradirectional processes involved in regulating interneurons in turn might lead to enhanced network excitability and promote synaptic plasticity.  

“Gamma oscillations have been shown to represent a basic mechanism to induce cell-specific plastic changes within a neuronal network,” explains Prof. Tengis Gloveli. He adds: “These changes reflect neuronal network activity, and are based on a mechanism whose key component is the excitatory metabotropic glutamate receptor 5.”

Dysregulation of the metabotropic glutamate receptor 5 has already been identified in several profound neurological disorders, such as schizophrenia, autistic spectrum disorders, and Down Syndrome. Data from the current study demonstrate that these receptors play a central role in network oscillation-induced synaptic plasticity and highlight them in the general context of memory processing. Additional research will be needed to further establish the effect of different cell types on synaptic plasticity and their impact on memory formation.