研究課題
In Heisei 28 we made significant progress. In fear conditioning, and auditory stimulus is paired with an aversive shock and animals exhibit fear responses to the tone after learning. However, if the tone is presented repeatedly in the absence of shock fear responding is extinguished. We've been studying how the brain knows to extinguish fear responses and have focused on the ventral tegmental area (VTA) dopamine system as potentially signaling when shocks don't occur to initiate extinction. In the previous year we found that inhibition of VTA dopamine neurons during the shock omission period of extinction blocked extinction learning (animals continued to be afraid of the tone. Last year we examined which downstream circuits these VTA dopamine neurons signaled to engage extinction. To do this we expressed an inhibitory opsin in the VTA dopamine neurons and inhibited their terminals in the nucleus accumbens (NAc). We first used voltammetry to show that dopamine released was inhibited in the NAc with optical inhibition of dopamine nerve terminals in the NAc. We then inhibited dopamine nerve terminals in the NAc during the shock omission period of extinction and found that this manipulation reduced the long term retention of extinction memories.
2: おおむね順調に進展している
Everything is going smoothly
In the next fiscal year we will examine the contribution of ventral tegmental area (VTA) dopamine projections to the amygdala and medial prefrontal cortex (mPFC) on fear and extinction learning. We will use a tyrosine hydroxylase-cre recombinase rat to express inhibitory opsins (Archaerhodopsin) in the VTA dopamine cells and their nerve terminals in the amygdala and mPFC. We will then inhibit the terminals of these cells in the amygdala and mPFC during either the shock period of fear conditioning or during the shock omission period of extinction and determine the effects of these manipulations on fear and extinction learning.
すべて 2017 2016
すべて 雑誌論文 (3件) (うち国際共著 3件、 査読あり 3件、 謝辞記載あり 2件) 学会発表 (4件) (うち国際学会 2件、 招待講演 4件)
Nature Neuroscience
巻: 20(1) ページ: 90-97
10.1038/nn.4439
Neuropsychopharmacology
巻: 42(4) ページ: 895-903
10.1038/npp.2016.238
巻: 19 ページ: 965-972
10.1038/nn.4308
