Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement

The majority of the cells in the brain are not neurons, but Glia (from "glue") cells, that support the structure and function of the brain.  Astrocytes ("star cells") are star-shaped glial cells providing many supportive functions for the neurons surrounding them, such as the provision of nutrients and the regulation of their chemical environment. Newer studies showed that astrocytes also monitor and modulate neuronal activity. For example, these studies have shown that astrocytes are necessary for the ability of neurons to change the strength of the connections between them, the process underlying learning and memory, and indeed astrocytes are also necessary for normal cognitive function. However, it is still unknown whether astrocytic activity is only necessary, or is it may also be sufficient to induce synaptic potentiation and enhance cognitive performance.

In a new study published in Cell, two graduate students, Adar Adamsky and Adi Kol, from Inbal Goshen's lab, employed chemogenetic and optogenetic tools that allow specific activation of astrocytes in behaving mice, to explore their role in synaptic activity and memory performance. They found that astrocytic activation in the hippocampus, a brain region that plays an important role in memory acquisition and consolidation, potentiated the synaptic connections in this region, measured in brain slices. Moreover, in the intact brain, astrocytic activation enhanced hippocampal neuronal activity in a task-dependent way: i.e. only during when it was combined with memory acquisition, but not when mice were at their home cage with no meaningful stimuli. The ability of astrocytes to increase neuronal activity during memory acquisition had a significant effect on cognitive function: Specifically, astrocytic activation during learning resulted in enhanced memory in two memory tests. In contrast, direct neuronal activation in the hippocampus induced a non-selective increase in activity (during learning or in the home cage), and thus resulted in drastic memory impairment.

The results suggest that the memory enhancement induced by astrocytic activation during learning is not simply a result of a general increase in hippocampal neuronal activity. Rather, the astrocytes, which sense and respond to changes in the surrounding neuronal activity, can detect and specifically enhance only the neuronal activity involved in learning, without affecting the general activity. This may explain why general astrocytic activation improves memory performance, whereas a similar activation of neurons impairs it.

Memory is not a binary process (remember/don't remember); the strength of a memory can vary greatly, either for the same memory or between different memories. Here, we show that activating astrocytes in mice with intact cognition improves their memory performance. This finding has important clinical implications for cognitive augmentation treatments. Furthermore, the ability of astrocytes to strengthen neuronal communication and improve memory performance supports the claim that astrocytes are able to take an active part in the neuronal processes underlying cognitive function. This perspective expands the definition of the role of astrocytes, from passive support cells to active cells that can modulate neural activity and thus shape behavior.

This article has been republished from materials provided by The Edmond and Lily Safra Centre for Brain Sciences, The Hebrew university of Jerusalem. Note: material may have been edited for length and content. For further information, please contact the cited source.