Neurons are the fundamental building blocks of the brain. They share information through electrical signals. After receiving a stimulus, the neurons are activated via changes in membrane voltage. This induces quick variations in membrane voltage that travel through the cell as an electrical signal. Subsequently, intracellular calcium varies as a result of these modifications in membrane voltage.
In the past, intrusive electrode approaches were needed to measure membrane voltage. Scientists have employed fluorescent proteins sensitive to calcium ions as a non-invasive way to assess neuron activity indirectly. However, because these techniques have usually been investigated independently, it is challenging to comprehend the real-time interactions between membrane voltage and calcium activity in living animals.
Researchers from Kyushu University collaborated with Kyushu Institute of Technology’s Faculty of Computer Science and Systems Engineering to create a technique that allows them to simultaneously detect intracellular calcium and membrane voltage in living animal neurons. Researchers used high-speed imaging at 250 frames per second and sophisticated image processing to detect minute changes in the fluorescence intensity of calcium ion and membrane voltage sensors.
This new method provides a more comprehensive understanding of neuron function, revealing that the two signals—calcium activity and membrane voltage—encode distinct information related to sensory stimuli.
The team mainly focused on how olfactory neurons in Caenorhabditis elegans respond to odorants. They found that these neurons change their membrane voltage and intracellular calcium levels when exposed to odors. These signals are also found to encode separate information.
Intracellular calcium levels showed the concentration of the odor, whereas membrane voltage showed its existence. By analyzing both signals simultaneously, the researchers were able to understand better how the brain interprets and distinguishes sensory inputs.
The team also identified two ion channels essential for changing membrane voltages triggered by sensory stimulation. A protein called ODR-3 found to play a crucial role in stabilizing membrane voltage. This mechanism prevents neurons from firing in response to irrelevant stimuli and helps regulate the timing and intensity of reactions to odors.
In the future, simultaneous membrane voltage and intracellular calcium measurements could be extended to neurons in more complex animals or different types of neurons, offering potential insights into how information is coded within neural circuits.
Senior author Professor Takeshi Ishihara from Kyushu University’s Faculty of Science said, “These high-speed simultaneous measurements reveal the different functions of the membrane voltage and intracellular calcium ion signals induced by the sensory stimuli. These findings could lead to a better understanding of sensory processing in the central nervous system, in simple model systems like nematodes and higher organisms.”
Journal Reference:
- Terumasa Tokunaga et al., Mechanism of sensory perception unveiled by simultaneous measurement of membrane voltage and intracellular calcium, Communications Biology (2024). DOI: 10.1038/s42003-024-06778-2
