Event Title

Alteration of fear and molecular signaling in the amygdala through the use of optogenetics

Mentor 1

Fred Helmstetter

Location

Union Wisconsin Room

Start Date

24-4-2015 10:30 AM

End Date

24-4-2015 11:45 AM

Description

Through pharmacological and lesion studies it is widely accepted that the lateral amygdala (LA) is required for the acquisition, consolidation, and retrieval of conditional fear memory. However, a major methodological issue with these types of studies is that inactivation of the amygdala leaves the structure either permanently damaged or inactivated for an imprecise amount of time. The creation of optogenetic techniques, which uses virally-expressed light sensitive ion channels and laser stimulation to either inhibit or excite neuronal activity, provides a more temporally precise method to study the amygdala’s role in memory. In the current study, we used the light-gated ion channel channelrhodopsin (AAV5-CaMKIIα-hChR2(H134R)-EYFP) to drive neuronal firing within the LA. We found that optogenetically exciting LA neurons resulted in increased immediate early gene (IEG) expression that mirrors IEG activity seen during the consolidation period following fear conditioning. We also used the light-driven proton pump ArchT (AAV9-CAG-ArchT-GFP), which when activated by light (523 nm), inhibits neuronal firing, during memory retrieval. Animals that expressed either ArchT or the control virus (expressing only GFP) were delay fear conditioned and then given a retrieval trial 24 hours following training. During retrieval, animals that expressed ArchT and were given laser stimulation during the retrieval session exhibited impaired conditioned fear expression compared to control animals. These results suggest that we are able to manipulate neuronal firing in the amygdala with precise temporal specificity to mimic behavioral impairments resulting from pharmacological manipulations to better elucidate the role of the amygdala during memory retrieval. Further, these data also demonstrate that we are able to artificially drive neural excitation and IEG expression within the amygdala to mirror learning induced excitation and gene activation that occurs during learning. A better understanding of the amygdala’s involvement in emotional learning can potentially lead to a better understanding of fear related disorders such as anxiety and PTSD. They also expand to help explain possible pathways for memory related disorders like Alzheimer’s.

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Apr 24th, 10:30 AM Apr 24th, 11:45 AM

Alteration of fear and molecular signaling in the amygdala through the use of optogenetics

Union Wisconsin Room

Through pharmacological and lesion studies it is widely accepted that the lateral amygdala (LA) is required for the acquisition, consolidation, and retrieval of conditional fear memory. However, a major methodological issue with these types of studies is that inactivation of the amygdala leaves the structure either permanently damaged or inactivated for an imprecise amount of time. The creation of optogenetic techniques, which uses virally-expressed light sensitive ion channels and laser stimulation to either inhibit or excite neuronal activity, provides a more temporally precise method to study the amygdala’s role in memory. In the current study, we used the light-gated ion channel channelrhodopsin (AAV5-CaMKIIα-hChR2(H134R)-EYFP) to drive neuronal firing within the LA. We found that optogenetically exciting LA neurons resulted in increased immediate early gene (IEG) expression that mirrors IEG activity seen during the consolidation period following fear conditioning. We also used the light-driven proton pump ArchT (AAV9-CAG-ArchT-GFP), which when activated by light (523 nm), inhibits neuronal firing, during memory retrieval. Animals that expressed either ArchT or the control virus (expressing only GFP) were delay fear conditioned and then given a retrieval trial 24 hours following training. During retrieval, animals that expressed ArchT and were given laser stimulation during the retrieval session exhibited impaired conditioned fear expression compared to control animals. These results suggest that we are able to manipulate neuronal firing in the amygdala with precise temporal specificity to mimic behavioral impairments resulting from pharmacological manipulations to better elucidate the role of the amygdala during memory retrieval. Further, these data also demonstrate that we are able to artificially drive neural excitation and IEG expression within the amygdala to mirror learning induced excitation and gene activation that occurs during learning. A better understanding of the amygdala’s involvement in emotional learning can potentially lead to a better understanding of fear related disorders such as anxiety and PTSD. They also expand to help explain possible pathways for memory related disorders like Alzheimer’s.