Neurons are the cells that make up neural circuits and use chemicals and electricity to receive and send messages that allow the body to do everything, including thinking, sensing, moving and more. Neurons have a long fiber called an axon that sends information to subsequent neurons. Information from axons is received by branch-like structures that fan out from the cell body, called dendrites.
Dendritic refinement is an important part of early postnatal brain development, where dendrites are tailored to make specific connections with appropriate axons. In a recently published paper, researchers present evidence showing how a mechanism in the neurons of a rodent involving the Golgi apparatus initiates dendritic refinement by means of the neuronal activity received by a receptor of a neurotransmitter called N-methyl-D- aspartate-type glutamate receptor (NMDAR).
The newspaper was published in Cell reports on July 28.
We wanted to find the cellular mechanism underlying 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.”
Naoki Nakagawa, assistant professor, National Institute of Genetics in Shizouka, Japan
The organelle in question is the Golgi apparatus, which acts as a hub for the transport of materials inside the cell. The location of the Golgi apparatus in a cell generates cell polarity by determining the direction of intracellular transport. “Golgi-mediated cell polarity has been known to play an important role in earlier embryonic developmental events, such as mitosis, migration and differentiation of cells,” Nakagawa said. “However, during the postnatal critical period of circuit reorganization, we did not know whether Golgi polarity is altered by neuronal activity or whether the Golgi polarity change contributes to the remodeling of neuronal circuits.”
To understand the role of Golgi polarity in dendritic refinement, researchers studied spiny stellate neurons in rodents. These neurons are found in a part of the rodent brain called the barrel cortex, which processes tactile information from whiskers. Spiny stellate neurons in the barrel cortex have asymmetric dendrites facing the center of the barrel. This unique dendritic structure is established during the first week after birth through refinement based on neuronal activity. To trace the location of the Golgi apparatus during postnatal development, the Golgi-targeted fluorescent protein was expressed in spiny stellate neurons.
In the first few days of life, the Golgi apparatus in spiny stellate cells became apically polarized during postnatal days 1 to 3, but ended laterally polarized toward the barrel center by postnatal day 5. By day 15, when the asymmetric dendrite pattern was already established, the lateral polarization decreased. Researchers also looked at the location of the Golgi apparatus in the dendrites. Dendrites that contained Golgi apparatuses at or near the base were longer and more branched than dendrites that did not.
Signals from the NMDAR are necessary for the lateral Golgi polarization, which in turn instructs the correct dendritic refinement. These were evident when researchers disrupted NMDAR signaling, or Golgi polarity. In both cases, the shape and direction of the dendrites changed in an inappropriate way.
Looking ahead, researchers want to uncover more about how the Golgi apparatus affects neuronal development. “We want to know how the neuronal activity moves the Golgi apparatus to the right positions in neurons and how the Golgi polarization enables the correct patterning of neuronal dendrites,” Nakagawa said. “We believe that tackling these questions will provide a better understanding of what happens in neurons during postnatal development and how it promotes circuit reorganization, which is an essential step for engineering sophisticated neuronal circuits in the brain.”
Takuji Iwasato at the Laboratory of Mammalian Neural Circuits at the National Institute of Genetics in Shizouka, Japan also contributed to this research.
JSPS KAKENHI, Uehara Memorial Foundation, and Takeda Science Foundation supported this research.