2021 Fiscal Year Research-status Report
Investigation of nucleus accumbens subpopulations controlling reward and aversive learning
| Project/Area Number |
21K15210
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| Research Institution | Osaka University |
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Principal Investigator |
マクファーソン トム 大阪大学, 蛋白質研究所, 助教 (40821898)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Keywords | Reward / Aversion / Learning / Nucleus Accumbens / Basal Ganglia |
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| Outline of Annual Research Achievements |
In this first year i was able to successfully image the neural activity of nucleus accumbens (NAc) D1- and D2- neurons during learning of a reward and aversion Pavlovian conditioning task in head-fixed mice. Specifically, a cre-dependent calcium indicator was infused into the NAc of 5 D1- and 5 D2-Cre mice, and a miniature microscope was used to image the calcium traces of NAc D1- and D2-neurons as mice performed a Pavlovian learning task in which three different auditory stimuli were paired with either a liquid reward, an airpuff punishment, or no outcome (control). Following acquisition of the task (as assessed by conditioned increased or decreases in licking of the reward spout during presentation of the reward- or aversion-paired tones, respectively), patterns of neural activity were dimensionally reduced using principle component analysis and hierarchically clustered to identify 8 functionally distinct NAc cell populations contributing to Pavlovian conditioning. Interestingly, many of these subpopulations contained both D1- and D2-neurons, indicating that both cell types cooperatively control reward and aversion signaling. These data provide a major update to previous simplistic models suggesting that NAc D1- and D2-neurons separately control reward and aversive learning, respectively.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
It was expected that by the end of year 1, approximately half of the miniature microscope imaging would be completed. In fact, I was able to complete all imaging necessary within the first year and have analyzed about half of the data. In addition, I have already begun work on the second part of the project, utilizing an activity- and cre-dependent method in D1- and D2-cre mice to express a channelrhodopsin in reward- and aversion-activated D1 and D2-neuron subpopulations in order to investigate whether artificial stimulation of such populations is able to drive reward- or aversion-related behaviors (i.e. seeking or avoidance behaviors). It is expected that these studies will continue to progress on or ahead of schedule.
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| Strategy for Future Research Activity |
In the next year, i will continue to analyze the imaging data. Specifically, I will compare neural activity in early training to that in late training to understand how patterns of neural activity in NAc D1 and D2-neurons change as a result of learning. Additionally, i will continue to perform optogenetic experiments using the activity- and cre-dependent expression system i have created to target NAc subpopulations. This will include stimulating these subpopulations during real-time place preference tests as well as investigating whether mice will instrumentally respond (lever press) in an operant chamber to acquire or avoid laser stimulation of these subpopulations. Finally, i will perform monosynaptic rabies tracing of these subpopulations to uncover the origin of their synaptic inputs.
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| Causes of Carryover |
In the last year, my work was mostly focused on performing the neural imaging experiments for my research project. For these experiments i was able to use equipment and materials that were already available in our lab and therefore i did not end up using a large amount of the money that had been allocated for this year. The money that was left over will be used for the purchase of two operant chambers in the next year that will allow me to speed up the performance of behavioral and optogenetic experiments that will be performed this year. In addition, this money will also be put towards the cost of publishing articles arising from this research project.
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Research Products
(1 results)
