Abstract Details

Title Regulation of Locomotion and Cortical State through Optogenetic Stimulation of the Pedunculopontine Nucleus (PPN)

Topic General Neurology

Presentation(s) S32 - General Neurology: Advances in Neurology: From the Clinic to the Bench (4:03 PM-4:14 PM)

Poster/Presentation
Number 004

Background The PPN contains a heterogeneous mix of cholinergic, glutamatergic and GABAergic neurons that contribute to cortical state and motor function via ascending and descending projections. Optogenetics allows for cell specific stimulation and millisecond temporal precision previously not possible with electrical stimulation and pharmacological methods. This enables the study of neuronal subpopulations and their role on behavior and cortical state for a complete understanding of mammalian locomotion control.

Objective Elucidate the effects of selective PPN activation through optogenetic stimulation of glutamatergic or GABAergic neuronal subpopulations. Specifically, we sought to study the downstream effects of PPN stimulation that lead to initiation and cessation of locomotion while concurrently recording upstream effects through the use of electroencephalography (EEG).

Design/Methods VGAT-cre and VGLUT-cre mice were injected in the PPN with adeno-associated virus carrying channelrhodopsin and implanted with fiber-optic ferrules at the site of injection. After a channelrhodopsin incubation period, mice were stimulated with a 473nm laser (5-second trains at 10 Hz). Locomotion and cortical EEG were continuously recorded through a camera and data acquisition system. Mice were allowed to move freely while tethered for EEG recording and light delivery via fiber-optics. Motion capture software was used to quantify distance traveled over time, and time-frequency analysis of EEG data was applied offline. After experimentation mice were perfused and prepared for immunohistochemical analyses.

Results Stimulation of PPN glutamatergic neurons resulted in a rapid increase in locomotion (609.9% ±102.6% of baseline N=10 trials), while GABAergic stimulation led to complete motor cessation. Additionally, time-frequency analysis of EEG data demonstrated changes in cortical state with PPN stimulation resulting from ascending projections.

Conclusions These data demonstrate that glutamatergic and GABAergic cells in the PPN play specific and unique roles in locomotion and cortical processing. Additionally, activation of neuron subpopulations in the PPN produces rapid and repeatable changes in locomotion and cortical processing.

Authors/Disclosures
Ana D. Collazo (US Army Medical Research Institute of Chemical Defense) PRESENTER	No disclosure on file
Justin Moreno (SURVICE Engineering)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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