In the brain, neurons and astrocytes work together to process information and enable complex behaviors and cognitive abilities. Astrocytes have many functions such as controlling the blood-brain barrier, supplying nutrients to nervous tissue and aiding in its repair. An interesting feature of astrocytes is that they form large networks of connected cells. These junctions consist of specific membrane pores formed by a group of proteins called connexins. And through these connections, astrocytes can communicate with each other by exchanging different ions and small molecules.
Switching off astrocyte coupling disrupts the formation of spatial memory
A team of neuroscientists led by Aiman Saab and Bruno Weber from the Institute of Pharmacology and Toxicology at the University of Zurich (UZH) have found that astrocyte coupling in the adult mouse brain contributes to neural function in the hippocampus, a brain region that contains the causes is involved in spatial memory formation. “We found that in adulthood, an intact astrocyte network is essential for neural homeostasis, synaptic plasticity, and spatial cognitive abilities of this brain region,” says Aiman Saab, senior author of the study.
To elucidate the functional importance of the astrocyte network, the researchers created a mouse model in which the two key connexins responsible for linking astrocytes can be selectively inactivated. Once the relevant genes were knocked out, astrocytes lost their ability to maintain intercellular networks, and astrocyte-to-astrocyte coupling was disrupted within a few weeks.
An intact astrocytic network is key to adult mouse brain function
The disruption of the astrocyte network altered the excitability of neurons in the hippocampus and their signaling at the synapses. In addition, the strengthening of these specialized neural connections needed to store synaptic information has also been compromised. This was accompanied by considerable deficits in the spatial learning and memory of the animals. “Astrocyte functions are known to be involved in shaping cognitive abilities. Our study now shows that an intact astrocyte network is crucial for spatial memory formation in adult mice,” says Ladina Hösli, first author of the study.
Striking similarities to neurodegenerative diseases and neuropsychiatric disorders
In addition, the primary immune cells of the brain are also affected by the loss of astrocyte coupling. The activation of these so-called microglia observed in mice resembles changes documented in neurodegenerative diseases such as Alzheimer’s disease and neuropsychiatric disorders such as depression. “Astrocytes and microglia not only changed their morphology, we also found changes in specific markers that are characteristic of disease-associated microglia,” says Hösli.
Since normal brain aging is also associated with changes in astrocytic coupling, these glial changes could contribute to age-related declines in learning and memory. “Our study shows that in the adult brain, the function of astrocyte connexins and an intact glial network may be important in the way astrocytes and microglia work together to maintain neural homeostasis,” says Aiman Saab. In a next step, the researchers want to understand how microglial functions change when astrocyte coupling is disrupted.