Optogenetics and Chemogenetics
Understanding Neural Activity: Recording and Manipulation Tools
GCaMP: A Calcium-Based Fluorescence Tool for Neural Activity Recording
GCaMP Functionality: GCaMP (Genetically Encoded Calcium Indicator) is an in vivo fluorescence tool that is calcium-based.
As neurons fire, they generate a spike in intracellular calcium concentration.
This calcium spike binds to the GCaMP protein.
Conformational changes in the GCaMP protein lead to a flux (change) in the fluorescence of an associated Green Fluorescent Protein (GFP), which is conjugated to GCaMP.
Direct Marker: GCaMP acts as a direct marker of neuron firing, allowing researchers to visualize neural activity.
Example Application: Observing activity in the visual cortex of an animal.
When an animal is moving and exploring its environment, significant coronal activations are observed in the visual cortex, indicating high neural activity (e.g., during visual exploration).
When the animal is still, a decrease in GCaMP fluorescence is typically seen, indicating reduced neural activity.
Limitation: Correlation vs. Causation: GCaMP provides only correlational evidence.
While you can observe neurons firing when an animal performs a behavior (e.g., visual cortex activity during movement), it does not causally prove that those specific neurons are driving the behavior.
This highlights the need for tools that can manipulate neural activity to establish causation.
Historical and Traditional Methods of Neural Manipulation
Challenges in Early Manipulation: Historically, manipulation methods were often