Optogenetic Approaches to Study IEG Activation

Immediate early genes (IEGs) are reliably activated by pathological events such as seizures, but the activity patterns that trigger IEG expression in individual neurons under physiological conditions are not well understood. Optogenetic stimulation allows controlling the activity of single neurons or groups of neurons. Different spike patterns can be imposed in channelrhodopsin-expressing neurons, while expression of photoactivated adenylyl cyclase (PACmn) allows to increase intracellular cyclic adenosine monophosphate (cAMP) in single neurons or populations of neurons. No microscope is required for these optogenetic stimulation experiments; an LED (light-emitting diode) light source within a cell culture incubator is sufficient. As application examples, we show that Fos expression in CA1 pyramidal cells is activated by synchronized excitatory input and that raising cAMP in a single neuron is not sufficient to induce Fos. We conclude that some IEGs are induced by network-level events rather than by autonomous activity of individual cells.