Summary: During periods of social isolation, astrocytes in the brain become hyperactive. This suppresses circuit formation and memory formation. Reversing astrocyte hyperactivity can help mitigate memory deficits associated with social isolation.
Source: Baylor College of Medicine
Here is an important reason to stay in touch with friends and family: social isolation causes memory and learning deficits and other behavioral changes. Many brain studies have focused on the effects social deprivation has on neurons, but little is known about the consequences for the most abundant brain cell, the astrocyte.
Researchers at Baylor College of Medicine working with animal models report in the journal Neuron that during social isolation, astrocytes become hyperactive, which in turn suppresses brain circuit function and memory formation. Importantly, inhibiting astrocyte hyperactivity reversed the cognitive deficits associated with social deprivation.
“One thing we have learned during the COVID pandemic is that social isolation can influence cognitive functions, as previous studies suggested,” said co-first author, Yi-Ting Cheng, graduate student in Dr. Benjamin Deneen’s lab at Baylor. “This motivated co-first author Dr. Junsung Woo and me to further investigate the effects of social isolation in the brain, specifically in astrocytes.”
Astrocytes play diverse roles in the brain such as supporting the functions of neurons, participating in synapse formation and function, releasing neurotransmitters and making the blood-brain barrier.
“Under normal group housing conditions, astrocytes facilitate and promote circuit function and memory,” said Deneen, professor and Dr. Russell J. and Marian K. Blattner Chair of neurosurgery and director of the Center for Cancer Neuroscience at Baylor. He also is the corresponding author of the work.
“However, we found that during social deprivation, astrocytes in the brain region known as the hippocampus actually suppress circuit function and memory formation. The broad conclusion is that astrocyte function is tuned to social experiences.”
Looking for a deeper understanding of the mechanism by which astrocytes of socially-isolated mice cause learning and memory deficits, the researchers studied calcium ions (Ca2+), which previous studies had shown play a central role in astrocyte-mediated learning and memory behaviors.
“We evaluated the effect of social deprivation on astrocyte Ca2+ activity and discovered that social isolation greatly increased it, specifically the activity involving Ca2+ channel TRPA1. This in turn was followed by the release of the inhibitory neurotransmitter GABA that put a break on neural circuits involved in memory and learning,” Cheng said.
“Importantly, both pharmacological and genetic inhibition of TRPA1 reversed the physiological and cognitive deficits associated with social deprivation.”
“Although social isolation also affects other brain cells, we are very excited about the discovery that specifically manipulating astrocytes is enough to restore learning and memory deficits triggered by social isolation in animal models,” Deneen said.
“Our findings show a new role for astrocytes in brain physiology,” Cheng said. “What astrocytes do is affected by changes in the environment and will reflect in the animal’s behavior. In this case, we learned that social interaction is good for astrocytes and therefore, for the brain.”
About this social isolation and memory research news
Social deprivation induces astrocytic TRPA1-GABA suppression of hippocampal circuits
Social deprivation alters molecular and cellular properties of hippocampal astrocytes
Astrocytic TRPA1 suppresses mouse hippocampal circuit function after social deprivation
TRPA1 mediates elevated tonic GABA release from astrocytes after social deprivation
Astrocytic GABA suppresses hippocampal circuit function after social deprivation
Social experience is essential for the development and maintenance of higher-order brain function. Social deprivation results in a host of cognitive deficits, and cellular studies have largely focused on associated neuronal dysregulation; how astrocyte function is impacted by social deprivation is unknown.
Here, we show that hippocampal astrocytes from juvenile mice subjected to social isolation exhibit increased Ca2+ activity and global changes in gene expression.
We found that the Ca2+ channel TRPA1 is upregulated in astrocytes after social deprivation and astrocyte-specific deletion of TRPA1 reverses the physiological and cognitive deficits associated with social deprivation.
Mechanistically, TRPA1 inhibition of hippocampal circuits is mediated by a parallel increase of astrocytic production and release of the inhibitory neurotransmitter GABA after social deprivation.
Collectively, our studies reveal how astrocyte function is tuned to social experience and identifies a social-context-specific mechanism by which astrocytic TRPA1 and GABA coordinately suppress hippocampal circuit function.