# Crosstalk Between Astrocytes and Inhibitory Neurons During Maturation: Emerging Mechanisms and Functional Implications

## TL;DR

This paper reviews how astrocytes and inhibitory neurons interact during brain development, suggesting these interactions are crucial for healthy brain maturation.

## Contribution

The paper highlights emerging mechanisms of astrocyte-inhibitory neuron crosstalk during development and proposes hypotheses for future research.

## Key findings

- Astrocytes and inhibitory neurons interact during critical developmental periods to shape brain circuitry.
- Glutamate release from excitatory neurons may trigger calcium responses in astrocytes, promoting inhibitory neuron maturation.
- Crosstalk between astrocytes and inhibitory neurons is evolutionarily conserved and developmentally timed.

## Abstract

Astrocytes, once regarded merely as passive support cells in the brain, have recently emerged as active partners to neurons in sensory processing, learning and memory. By promoting the development, maturation and refinement of neuronal synapses, astrocytes play a central role in shaping brain circuitry. Within these circuits, inhibitory neurons comprise approximately 20% of brain cells, with variation across regions and developmental stages. The fundamental importance of inhibition is underscored by its evolutionary conservation, being present even in primitive nervous systems. Notably, astrocyte development coincides temporally with a peak in synaptogenesis and with the maturation of inhibitory neurons, suggesting potential interplay between these processes. Historically, research has primarily focused on astrocyte interactions with excitatory neurons; however, there is growing recognition of the likely significance of astrocyte–inhibitory neuron crosstalk, particularly during critical developmental periods. Here we review current knowledge on the development of astrocytes and inhibitory neurons, highlight emerging evidence for their interactions and propose hypotheses to guide future research.

In this review, we discuss the development and maturation of inhibitory neurons and astrocytes and how early developmental activity in the brain might promote the interactions between these cell types. Early in development, excitatory neurons are the first to emerge. As they migrate and mature into their set places, glutamate is released into the extracellular environment. Precursors for inhibitory neurons which will later become parvalbumin (PV+) or somatostatin (SST+) neurons begin to emerge and migrate. Once astrocytes emerge, they respond to glutamate release from excitatory neurons with increases in calcium. Our hypothesis is that this enables inhibitory neurons to mature. Future research is needed to understand these complex reciprocal interactions that promote a healthy and mature brain.