Recent research has unveiled a significant breakthrough in understanding how brain circuits maintain stability in adulthood. A study published in the journal Nature identifies the astrocyte-secreted protein CCN1 as a crucial factor in stabilizing neural circuits in the adult brain. This discovery could pave the way for new therapeutic approaches to neurological disorders such as Alzheimer’s disease, depression, and post-traumatic stress disorder (PTSD).
Researchers at the Salk Institute have been investigating the role of astrocytes, non-neuronal brain cells traditionally viewed as mere support structures. The findings indicate that astrocytes actively contribute to the maintenance of sensory circuit stability as individuals age. “This study establishes the crucial role of astrocytes in actively stabilizing the connectivity of neuronal circuits,” stated Nicola Allen, PhD, the corresponding author and co-director of the Neuroimmunology Initiative funded by the NOMIS Foundation at Salk.
The study highlights how mammalian sensory circuits experience higher plasticity during youth, which is essential for circuit refinement. As individuals mature, neural connectivity becomes more stable but less plastic. While stability is vital for functional connectivity, the potential for re-opening plasticity exists through methods such as enzymatic digestion of the extracellular matrix or the transplantation of juvenile astrocytes.
To explore the role of astrocytes in this process, the researchers focused on the mouse visual cortex. They combined a transcriptomic approach with ex vivo electrophysiology and in vivo imaging to assess the effects of CCN1. The results revealed that increased expression of CCN1 led to enhanced cellular maturation in both inhibitory neurons and oligodendrocytes, which subsequently reduced the neuroplasticity of the circuits.
Conversely, the absence of astrocyte CCN1 in adult mice destabilized binocular circuits and diminished myelination. This suggests that manipulating CCN1 levels could enable researchers to control neuroplasticity, facilitating the recovery of neural circuits following injury or trauma. CCN1 is known to bind with various extracellular components across different cell types, including excitatory and inhibitory neurons, oligodendrocytes, and microglia.
By interacting with integrin proteins on cell surfaces, CCN1 coordinates the maturation of multiple cell types, which in turn reduces the adult brain’s plasticity. “Maintaining stable circuits is important for proper brain function, but the consequence is that neural plasticity and remodeling are repressed in the adult brain,” explained Laura Sancho, PhD, the first author and a postdoctoral researcher in Allen’s lab. “We wanted to find out if and how astrocytes participate in this critical maintenance, and we found they are in fact essential.”
The implications of this research extend beyond basic science, possibly informing the development of therapeutic strategies for brain injuries and conditions affecting neuroplasticity. As scientists work to understand the complexities of the adult brain, findings such as those from the Salk Institute could lead to transformative advancements in treating neurological disorders.
