Optogenetic Control of Hippocampal Network Dynamics

Begin with a mouse hippocampal slice containing the target pyramidal cells connected to genetically modified light-sensitive interneurons.

Place the slice in a recording chamber.

Position a local field potential or LFP electrode in the desired region to record theta oscillations, a type of rhythmic brain activity.

Using a microelectrode, patch a nearby pyramidal cell to record its activity.

Place an optic fiber light above the hippocampal slice centered on the recording region.

Deliver blue light pulses at a set frequency to the slice to activate the light-sensitive ion channels in the interneuron.

The activation causes an influx of positive ions, leading to depolarization.

This triggers the release of inhibitory neurotransmitters onto the pyramidal neuron, thereby reducing excitability.

The light stimulation enhances the synchronization of the theta oscillations and the synaptic activity of the recorded neuron, suggesting effective modulation of the neural rhythms.

In this procedure, place an LFP electrode in the CA1 subiculum area, and patch a nearby pyramidal cell in the isolated hippocampus of a mouse expressing the blue light sensitive excitatory opsin ChR2 in PV interneurons.

Place an optic fiber light guide above the hippocampal preparation, and center it on the recorded region. Use blue light from an LED source for up to genetic stimulation, which consists of 10 to 20-millisecond light pulses or sine wave voltage commands delivered at theta frequencies. In current clamp, characterize the activity of the recorded cell during spontaneous theta oscillations. Then, start the stimulation protocol and record the light responses.

Observe that field oscillations and synaptic activity in the recorded neuron become increasingly synchronized during optogenetic stimulation, and that rhythmic pacing of PV cells results in a robust control of both frequency and power of theta oscillations.