High-Frequency Stimulation to Enhance Neuronal Activation and Neurogenesis in the Mouse Dentate Gyrus

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Begin with an awake mouse inside a stimulation setup.

The mouse is implanted with a deep brain stimulation electrode in the hippocampal dentate gyrus region.

Connect the implanted electrode to a programmable stimulator via leads.

Initiate the stimulation.

In the dentate gyrus, the electrical pulses trigger neurotransmitter release from presynaptic neurons, which bind to postsynaptic receptors.

This facilitates calcium influx into postsynaptic neurons, enhancing synaptic activity.

Repeated stimulation leads to prolonged calcium influx in postsynaptic neurons.

This initiates a signaling cascade that promotes the trafficking of excitatory neurotransmitter receptors to the postsynaptic terminal, thereby strengthening synaptic connections.

The pulses also stimulate the glial cells to release factors that support the formation of new neurons.

These factors also help integrate the new neurons into the existing neuronal network, improving memory and cognitive ability.

Upon completion of stimulation, disconnect the stimulator leads from the electrode.

To deliver stimulation, connect the implanted electrode to a programmable stimulator via leads.

Set up the software interface. Then, set the HFS parameters as six series of six trains of six pulses at 400 Hertz, and the stimulation intensity of 200 milliamps. Deliver HFS for the desired period of time as set up.

For the control group, implant electrodes in the mice without delivering any stimulation. For C-fos staining, stimulate the experimental mice two times for one day. For BrdU labeling, apply appropriate stimulations to both the acute stimulation group and the chronic stimulation group.

During the course of the stimulation, make sure the mouse is awake. Remember to ensure the leads are not twisted. When the stimulation is done, carefully disconnect the electrode pin from the electrode holder in the connector of the recording system.

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Last updated: 27 June 2026