New Research Uncovers Mechanism Behind Dendritic Refinement in Neurons
Scientists have made a significant discovery regarding the development of neural circuits in the early postnatal brain. In a paper published in Cell Reports, researchers reveal how the Golgi apparatus, an organelle within neurons, plays a crucial role in initiating dendritic refinement.
Neurons are responsible for transmitting and receiving messages in the body through the use of chemicals and electricity. Dendrites, branch-like structures that extend from the cell body, receive information from axons, the long fibers that send messages to subsequent neurons.
During early brain development, dendritic refinement occurs, which involves tailoring dendrites to form specific connections with appropriate axons. The recent study highlights how the Golgi apparatus, in conjunction with neuronal activity, orchestrates this refinement process.
“We wanted to find the cellular mechanism that underlies activity-dependent neuronal circuit reorganization during early postnatal brain development. The potential contribution of the dynamics of subcellular structures, such as organelles, to this process has been largely overlooked,” explains Naoki Nakagawa, Assistant Professor at the National Institute of Genetics in Shizouka, Japan.
The Golgi apparatus, known for its role in intracellular transport, influences cell polarity by determining the direction of material movement within cells. The researchers aimed to investigate whether the Golgi apparatus also played a role in remodeling neuronal circuits during the postnatal critical period.
To study this, the scientists examined spiny stellate neurons in rodents located in the barrel cortex, which processes tactile information from whiskers. These neurons have asymmetrical dendrites that face the barrel center, and this unique dendritic structure is established through refinement based on neuronal activity during the first week after birth.
The researchers expressed a Golgi-targeted fluorescent protein in the spiny stellate neurons to track the positioning of the Golgi apparatus during postnatal development. They observed that the Golgi apparatus initially exhibited apical polarization but later shifted to lateral polarization toward the barrel center. By day 15, when the asymmetrical dendrite pattern was already established, the lateral polarization diminished.
Furthermore, the placement of the Golgi apparatus within the dendrites was found to influence their length and branching. Dendrites containing the Golgi apparatus inside or at the base were longer and more branched than those without.
It was also discovered that signals from a receptor called the N-methyl-D-aspartate-type glutamate receptor (NMDAR) were required for the lateral polarization of the Golgi apparatus. Inhibiting either the NMDAR signal or the Golgi polarity disrupted the proper dendritic refinement.
The findings shed light on the intricate relationship between the Golgi apparatus, neuronal activity, and dendritic refinement. The researchers aim to further investigate how neuronal activity influences the positioning of the Golgi apparatus within neurons and how Golgi polarization enables the proper patterning of neuronal dendrites.
“We think that addressing these questions will provide a better understanding of what is happening within neurons during postnatal development and how it promotes circuit reorganization, which is an essential step for constructing sophisticated neuronal circuits in the brain,” says Nakagawa.
The research was conducted by scientists at the National Institute of Genetics in Shizouka, Japan, including Naoki Nakagawa and Takuji Iwasato. It was supported by the JSPS KAKENHI, the Uehara Memorial Foundation, and the Takeda Science Foundation.
Further studies in this area could lead to a deeper understanding of brain development and potentially contribute to advancements in neurological disorders and treatments.