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Markers of Neuronal Activity and Their Use in Brain Research
Neuronal activity constitutes the core of brain function, playing a crucial role in encoding, processing, and transmitting information that underpins complex behaviors such as perception, cognition, learning, and memory. Studying neuronal activity not only deepens our understanding of fundamental brain mechanisms but also provides valuable insights for developing therapies to treat neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Table 1 summarizes key neural markers, detailing their types, localization, functions, and common applications in neuroscience research.
Table 1 Key markers and their characteristics.
| Marker | Type | Localization/Function | Application |
|---|---|---|---|
| NeuN | Nucleoprotein | Mature neuronal nuclei, regulates RNA splicing | Neuron counting, neurodegenerative disease diagnosis |
| MAP2 | Microtubule-associated protein | Dendritic skeleton, stabilizes microtubule structure | Dendritic morphology research, plasticity analysis |
| TUJ1 | βIII-tubulin | Axonal and dendritic cytoskeleton | Neuronal migration and axonal guidance |
| NSE | Glycogen synthase | Cytoplasm, involved in energy metabolism | Neuronal injury marker |
| c-Fos | Early gene | Nuclear transcription factor | Marker of recent neuronal activity |
| Arc | Early gene | Postsynaptic cytoplasm, regulates AMPA receptors | Synaptic plasticity research |
| CD4-tdGFP | Membrane-localized fluorescent protein | Plasma membrane | In vivo neuronal morphology imaging |
| βIII-Tubulin | Cytoskeletal protein | Axonal guidance | Neural development and regeneration |
To advance this critical area of neuroscience research, Creative Biolabs offers a comprehensive range of cutting-edge products and services, including specialized detection methods, cell models, and advanced technologies, designed to support the exploration of neuronal function and brain health. Our expertise and innovative platforms enable researchers to explore neural circuits and monitor neuronal activity.
Overview of Neuronal Activity Markers
Neuronal activity markers are key tools for revealing the dynamics of brain function. By specifically identifying activated neuronal populations, they provide a spatially and temporally resolved window into understanding cognitive and behavioral mechanisms as well as disease mechanisms.
They are primarily divided into two major categories: molecular markers and functional imaging probes.
Molecular Markers
- Constitutive markers: identify neuronal identity (e.g., NeuN, MAP2) and are independent of activity status.
- Activity-dependent markers: respond to neuronal activation (e.g., c-Fos, Arc) and reflect real-time or recent neural activity. c-Fos, the most widely used activity marker, reaches peak expression 30–60 minutes after neuronal depolarization and regulates downstream genes through the AP-1 transcription complex.
Functional Imaging Probes
- Calcium indicators (GCaMP series): Fluorescence intensity increases with rising intracellular Ca²⁺ concentration, indirectly reflecting action potentials.
- Voltage-sensitive dyes (ANNINE dyes): Directly capture millisecond-scale changes in membrane potential.
- Integrative probes (e.g., CaMPARI): Permanently label activated neurons.
Technical Principles of Neuronal Activity Markers
Technical principles of neuronal activity markers mainly rely on detecting changes in calcium ion concentration and membrane potential.
- Calcium imaging technology uses calcium ion indicators (such as GCaMPs) that are fluorescent when binding to calcium ions, indicating neuronal activity. Changes in calcium ion concentration are often associated with firing of the neuron, so calcium imaging can indirectly detect neuronal activity.
- Voltage imaging technology uses voltage-sensitive fluorescent dyes that respond to changes in membrane potential, which directly reflects changes in neuronal membrane potential.
Calcium Imaging Technology
Figure 1 Principle of calcium imaging.
Table 2 Probe types of calcium imaging technology
| Category | Representative Probe | Features |
|---|---|---|
| Chemical Indicator | Fura-2 | Requires loading, prone to dissipation |
| Genetically Encoded Probe | GCaMP6s | Cell-specific expression, high signal-to-noise ratio |
The limitation of calcium imaging technology lies in the slow decay of calcium signals (seconds), making it difficult to capture high-frequency discharges.
Voltage Imaging Technology
The advantage of voltage imaging technology is that it can directly measure membrane potential and can detect subthreshold activity. The disadvantage is that scattering of tissue causes low spatial resolution and low signal-to-noise ratio. Use of two-photon + ANNINE dye to enhance the spatial resolution (super-resolution voltage imaging) can circumvent the limitation of tissue scattering.
Figure 2 Technologies for recording neuronal activity in rodents.1,2
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Core Application Scenarios in Brain Function Research
Neuronal activity markers have their application scenarios in brain function research, such as learning and memory, sensory processing, and so on. For example,
- c-Fos, as an activity marker, can show the activated state of neurons in response to specific stimuli and has been widely used in studies on learning and memory, fear, and addiction.
- Researchers can also use functional magnetic resonance imaging (fMRI) to find the active areas of the brain under certain tasks or stimuli to understand the connections and collaborations between different brain regions.
- In the study of learning and memory mechanism, LTP and LTD are two main molecular and cellular mechanisms, and neuronal activity markers can help to detect these processes.
- Fluorescent protein markers such as CaMPARI can detect neuronal activity in real time and provide a powerful tool for studying neural circuits and behavior.
In the research of neurodegenerative disease models, neuronal activity markers are widely used in the early diagnosis and observation of pathological features. In Alzheimer's disease and Parkinson's disease research, EEG signals are used to estimate the synchrony of neural activity as biomarkers for Alzheimer's disease, and the intensity of synchrony is measured to evaluate motor impairment in Parkinson's disease.
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Neuronal Activity Markers vs. Traditional Electrophysiological Techniques
Neuronal activity markers and traditional electrophysiological techniques each have their own advantages and disadvantages in the study of neuronal function and are suitable for different research scenarios.
Table 3 Comparison of neuronal activity markers and traditional electrophysiological techniques
| Neuronal activity markers | Electrophysiological techniques | |
|---|---|---|
| Spatial resolution | Single cell to subcellular (imaging techniques) | Single cell (patch clamp) or multi-unit (MEA) |
| Temporal resolution | Milliseconds to seconds (voltage imaging > calcium imaging) | Submillisecond (direct action potential recording) |
| Invasiveness | Non-invasive (optical imaging) or minimally invasive (viral vector) | Requires electrode implantation |
| Capacity | Can simultaneously record thousands of neurons | Typically, <100 channels |
| Applications | In vivo behavioral studies, long-term tracking | Ex vivo mechanism research, precise stimulation |
In recent years, there have been considerable advances in multi-omics integration technologies, such as spatiotemporal transcriptomics integrated with early stress gene (IEG) markers, allowing for an in-depth description of the spatiotemporal maps of activation-networks specific to brain regions. Dynamic monitoring technologies also enable an exceptional level of spatiotemporal resolution in the real-time tracking of neuronal activity. Machine learning models integrated with molecular markers provide new directions in predicting the progression of complex neurodegenerative diseases such as Alzheimer's.
At Creative Biolabs, we utilize these novel techniques to facilitate your research and drug development. Contact us today and see how our cutting-edge platforms and expert team can help accelerate your neuroscience and neuroinflammation research.
References
- Roth, Richard H., and Jun B. Ding. "From Neurons to Cognition: Technologies for Precise Recording of Neural Activity Underlying Behavior." BME Frontiers, vol. 2020, Jan. 2020, p. 7190517. DOI.org, https://doi.org/10.34133/2020/7190517.
- Distributed under Open Access license CC BY 4.0, without modification.
Created June 2025
For Research Use Only. Not For Clinical Use.