Astrocytes play a direct role in the regulation of neuronal circuits involved in learning and memory, according to new research from Baylor College of Medicine and M.D. Anderson Cancer Center.

Huang et al reveal region-specific transcriptional dependencies for astrocytes and identify astrocytic NFIA as a key transcriptional regulator of hippocampal circuits. Image credit: Huang et al, doi: 10.1016/j.neuron.2020.03.025.

Astrocytes are star-shaped glial cells in the brain and spinal cord.

They have unique cellular, molecular and functional properties and outnumber neurons by over fivefold. They occupy distinct brain regions, indicating regional specialization.

There is evidence suggesting that transcription factors proteins involved in controlling gene expression regulate astrocyte diversity.

A team led by Professor Benjamin Deneen from Baylor College of Medicine looked to get a better understanding of the role transcription factor NFIA, a known regulator of astrocyte development, played in adult mouse brain functions.

The researchers worked with a mouse model they had genetically engineered to lack the NFIA gene specifically in adult astrocytes in the entire brain.

They analyzed several brain regions, looking for alterations in astrocyte morphology, physiology and gene expression signatures.

We found that NFIA-deficient astrocytes presented defective shapes and altered functions, Professor Deneen said.

Surprisingly, although the NFIA gene was eliminated in all brain regions, only the astrocytes in the hippocampus were severely altered. Other regions, such as the cortex and the brain stem, were not affected.

Astrocytes in the hippocampus also had less calcium activity calcium is an indicator of astrocyte function as well as a reduced ability to detect neurotransmitters released from neurons.

NFIA-deficient astrocytes also were not as closely associated with neurons as normal astrocytes.

Importantly, all these morphological and functional alterations were linked to defects in the animals ability to learn and remember, providing the first evidence that astrocytes are to some extent controlling the neuronal circuits that mediate learning and memory.

Astrocytes in the brain are physically close to and communicate with neurons. Neurons release molecules that astrocytes can detect and respond to, Professor Deneen said.

We propose that NFIA-deficient astrocytes are not able to listen to neurons as well as normal astrocytes, and, therefore, they cannot respond appropriately by providing the support needed for efficient memory circuit function and neuronal transmission. Consequently, the circuit is disrupted, leading to impaired learning and memory.

The findings were published online in the journal Neuron.

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Anna Yu-Szu Huang et al. Region-Specific Transcriptional Control of Astrocyte Function Oversees Local Circuit Activities. Neuron, published online April 21, 2020; doi: 10.1016/j.neuron.2020.03.025

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