[8] Further modifications of GCaMP, including GCaMP3, GCaMP5, GCaMP6, and jGCaMP7, have been developed to progressively improve the signal, sensitivity, and dynamic range of Ca2+ detection,[2][9][10][11] with recent versions exhibiting fluorescence similar to native GFP.
Since the GCaMP calmodulin domain, when unbound, disrupts L-type calcium channel gating, the added calmodulin-binding motif prevents GCaMP-X from interfering with calcium-dependent signaling mechanisms.
[20] 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.
[21] GCaMP has played a vital role in establishing large-scale neural recordings in animals to investigate how activity patterns in neuronal networks influence behavior.
[22] 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.
[23] 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.
[32] For instance, Clarkson et al. (2017) used this method to show that neurons in the arcuate nucleus of the hypothalamus synchronize to increases in Ca2+ immediately prior to pulses of luteinizing hormone (LH).
[35] For instance, Tallini et al. (2006) expressed GCaMP2 in mouse embryos to show that, at embryonic day 10.5, electrical conduction was rapid in the atria and ventricles but slow in the atrioventricular canal.
[36] However, uncontrolled expression of GCaMP leads to cardiac hypertrophy due to overexpression of the calmodulin motif, which interferes with intracellular calcium signaling.
[37] Similarly, Greer and Bear et al. (2016) used GCaMP to characterize the dynamics of Ca2+ influx in necklace olfactory neuron signaling, which uses transmembrane MS4A proteins as chemoreceptors.