What's the science?
Astrocytes can do more than just surround and insulate neurons: they can actually sense and modify neuronal activity. Memory disruption is easy to produce; however, techniques that can enhance memory are rare. Previous work suggests that astrocytes are required for long-term potentiation and memory. Whether astrocytes may also be able to induce long-term potentiation on their own, however, is unclear. This week in Cell, Adamsky, Kol and colleagues test whether activation of astrocytes using chemogenetics is sufficient to induce potentiation in neurons and enhance memory.
How did they do it?
The authors used a chemogenetic (chemically engineering molecules) approach in mice: they expressed a G-protein coupled receptor specifically in astrocytes, and used this engineered receptor to activate astrocytes in the CA1 region of the hippocampus (important for memory) via increasing their intracellular calcium levels. They measured the excitatory post-synaptic currents in neurons in the hippocampus using whole-cell patch clamp and field recordings. These experiments allowed them to observe whether there was any long-term potentiation (plasticity required for memory) as a result of the astrocyte activation compared to control slices without astrocyte activation. Lastly, they tested to see whether chemogenetic astrocyte activation had any effect on spatial (a maze exploration task) and contextual memory (fear conditioning).
What did they find?
There was a 50% increase in the excitatory post-synaptic current amplitude of hippocampal neurons after astrocyte activation, demonstrating that astrocyte activation was sufficient to induce long-term potentiation. No similar potentiation was seen in control slices. This potentiation lingered long after the astrocytes were no longer activated, and was mediated by the same mechanisms of 'regular' potentiation (i.e. via the NMDA receptor). Mice treated to induce astrocyte activation 30 minutes prior to a maze task, performed significantly better than control mice. These mice also showed 40% more freezing (indicating enhanced memory of the context in which the foot shock was delivered ) than control mice. Astrocyte activation induced memory enhancement only when induced before acquisition (not before recall) showing that the astrocyte activation plays an important role during the learning process, rather than the retrieval. They then tested whether general neuronal activation (not astrocytic) has any effect on potentiation and memory to see whether these effects were specific to astrocytes and found that increasing neuronal activation did not enhance memory, but rather impaired it. They showed that this is due to the fact that astrocytic activity increases neuronal activity in a task-dependent manner - only in learning mice, but not in home-caged mice. Finally, they used optogenetics (which has better temporal resolution) to test whether astrocyte activation was enhancing memory specifically at the acquisition stage, and found it to induce an even bigger improvement in the contextual memory task.
What's the impact?
This is the first study to show that astrocyte activation is sufficient to produce long-term potentiation in hippocampal neurons and enhance memory performance. Previous research showed that astrocyte inhibition could impair memory, however, now we know that astrocytes alone can induce memory enhancement and that astrocytes may be more important for cognitive function than we once thought. Astrocyte activation could be one target for developing memory-enhancing drugs.
Adamsky, Kol et al., Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement. Cell (2018). Access the original scientific publication here.