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Research links gene activity variations in neural networks to functional disparities

Researchers at the Picower Institute for Learning and Memory discovered distinct gene expression patterns in two neuronal subtypes. By modifying genes with the most prominent difference in expression, scientists were able to illustrate the mechanisms behind key differences between these cell types.

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Researchers at the Picower Institute for Learning and Memory discovered that two neuronal subtypes...
Researchers at the Picower Institute for Learning and Memory discovered that two neuronal subtypes exhibited distinct gene expression patterns, with over 800 genes differing between them. By modifying genes showing the most prominent differences, scientists were successful in demonstrating the origins of various cellular distinctions.

Figuring out the intricate dance of cell growth and function in hundreds of brain cell types promises to reveal amazing insights into brain workings, both in good health and in disease. A recent MIT study, published in Neuron, explores this complexity by diving deep into two similar neuron types in the Drosophila fruit fly. These neurons, both specialized muscle controllers, differ in several aspects, as the study reveals.

In the MIT lab of Troy Littleton, Menicon Professor of Neuroscience, lead researcher Suresh Jetti worked to understand precisely how these two neurons, phasic and tonic, developed their unique properties. Both neurons connect to muscles through glutamate synapses, but they differ significantly in their main functions; phasic neurons connect to many muscles and release big, bursts of glutamate, while tonic neurons connect to a single muscle and offer a more constant release. These differences in functionality are reflected in various observable differences between the cell types.

The team began with a detailed examination of the cells' physical differences, comparing their formation, structural complexity, and connections. The tonic neurons, for instance, had more synapses on a single muscle but made fewer synapses overall, due to their smaller network. Meanwhile, phasic neurons had more dendrites reaching out to other neurons and produced more powerful signals when stimulated. Interestingly, the team discovered that the synaptic sites for glutamate release, called active zones (AZs), took in more calcium ions in phasic neurons than in tonic neurons, which may be linked to the bursts of glutamate release in phasic neurons.

To better understand the genetic differences between the cells, Jetti employed a precise RNA sequencing technique, isolating RNA from the same tonic and phasic neurons in hundreds of flies. In total, the expression of 822 genes was significantly different between the two neuron types. Some of these genes helped guide the growth of the axon branches, explaining the fewer, yet stronger connections in tonic neurons. Others controlled the structure and function of synapses, while yet more genes suggested differences in the neuromodulatory chemicals each neuron was sensitive to.

The team then set out to learn what these differently expressed genes did by disrupting their function and observing the resulting changes in the cells. For instance, interfering with specific genes led to overgrowth in phasic neuron synapses, while others caused synaptic undergrowth in tonic neurons. Several experiments allowed the team to distinctly disrupt each cell's AZ shapes by interfering with cytoskeletal genes each neuron expressed especially highly.

In all, the analysis began to unravel the molecular differences that contribute to the unique properties of these two neuronal subtypes in Drosophila. These insights could help clarify the functioning of human neurons as well, potentially offering new avenues for understanding and treating brain disorders.

The study was funded by the JPB Foundation, The Picower Institute for Learning and Memory, and the National Institutes of Health.

  1. The MIT lab of Troy Littleton, Menicon Professor of Neuroscience, conducted research on two neuron types, phasic and tonic, to understand their unique properties in the context of neuroscience and learning.
  2. Both phasic and tonic neurons connect to muscles through glutamate synapses, but they exhibit significant differences in functionality, with phasic neurons releasing large, bursts of glutamate and tonic neurons offering a more constant release.
  3. In their research, the team discovered that the synaptic sites for glutamate release, called active zones (AZs), took in more calcium ions in phasic neurons than in tonic neurons, which may be linked to the bursts of glutamate release in phasic neurons.
  4. Through RNA sequencing, the team identified 822 genes with significantly different expression between the two neuron types, many of which were associated with guiding axon growth, controlling synapse structure and function, and regulating sensitivity to neuromodulatory chemicals.
  5. The team's findings may have implications for understanding and treating brain disorders, as these insights could potentially clarify the functioning of human neurons and offer new avenues for medical-condition research in health and wellness.
  6. The study, which was funded by the JPB Foundation, The Picower Institute for Learning and Memory, and the National Institutes of Health, was published in the respected science journal Neuron, further highlighting its significance and potential impact in the field of science.

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