In neurons, action potentials induce neurotransmitter release at axon terminals by opening voltage-gated Ca channels, allowing for Ca influx. As a result, GCaMP is commonly used to measure increases in intracellular Ca in neurons as a proxy for neuronal activity in multiple animal models, including Caenorhabditis elegans, zebrafish, Drosophila, and mice. Recently, genetically encoded voltage indicators (GEVIs) have been developed alongside GECIs to more directly probe neuronal activity at the cellular level in these animal models.
GCaMP has played a vital role in establishing large-scale neural recordings in animals to investigate how activity patterns in neuronal networks influence behavior. For example, Nguyen et al. (2016) used GCaMP in whole-brain imaging during free movement of C. elegans to identify neurons and groups of neurons whose activity correlated with specific locomotor behaviors.
Muto et al. (2003) expressed GCaMP in zebrafish embryos to measure and map the coordinated activity of spinal motor neurons to different parts of the brain during the onset, propagation, and recovery of seizures induced by pentylenetetrazol. GCaMP expression in zebrafish brains has also been used to study activation of neural circuits in cognitive processes like prey capture, impulse control, and attention.
Additionally, researchers have used GCaMP to observe neuronal activity in mice by expressing it under control of the Thy1 promoter, which is found in excitatory pyramidal neurons. For instance, integration of neurons into circuits during motor learning has been tracked by using GCaMP to observe synchronized fluctuation patterns in Ca levels. GCaMP has also been used to observe Ca dynamics in subcellular compartments of mouse neurons: Cichon and Gan (2015) used GCaMP to show that neurons in the mouse motor cortex exhibit NMDA-driven increases in Ca that are independent for each dendritic spine, thus showing that individual dendritic spines regulate synaptic plasticity. Finally, GCaMP has been used to identify activity patterns in specific regions of the mouse brain. For instance, Jones et al. (2018) used GCaMP6 in mice to measure neuronal activity in the suprachiasmatic nucleus (SCN), the mammalian circadian pacemaker, and showed that SCN neurons that produced vasoactive intestinal peptide (VIP) exhibited daily activity rhythms in vivo that correlated with VIP release.
GCaMP has also been combined with fiber photometry to measure population-level Ca changes within subpopulations of neurons in freely moving animals. For instance, Clarkson et al. (2017) used this method to show that neurons in the arcuate nucleus of the hypothalamus synchronize to increases in Ca immediately prior to pulses of luteinizing hormone (LH). While GCaMP imaging with fiber photometry cannot track changes in Ca levels within individual neurons, it provides greater temporal resolution for large-scale changes.