活動
期刊試閱範本
班別：生科三A       學號：000888     姓名：唐世杰
Presynaptic Excitation via GABAB Receptors in Habenula Cholinergic Neurons Regulates Fear Memory Expression
Cell Volume 166, Issue 3, p716–728, 28 July 2016
恐懼的記憶與GABA和鈣離子通道有關,有趣。
重點提示Highlights
  1. Habenula cholinergic neurons減緩恐懼記憶的表現。
  2. 在habenula neurons中的Presynaptic GABAB的活性，執行恐懼的滅除。
  3. GABAB強烈地增進共同釋放多種神經傳導物質。
  4. GABAB 放大presynaptic鈣離子經由Ca++2.3離子通道進入。
    摘要
    恐懼的行為由適應性機制調控，在缺少危機時降低其表現。在研究思考線路和分子機制的適應反應，作者顯示medial habenula cholinergic神經經由GABAB presynaptic活化減少恐懼記憶的表現。在老鼠中，切除這些神經與抑制GABAB接受體活化，可削弱恐懼的去除。反之，活化這些神經與GABAB接受體，可減少條件式的恐懼。GABAB經由放大presynaptic鈣離子經Cav2.3鈣離子通道進入和促進共同釋放 glutamate, acetylcholine, 和neurokinin B活化interpeduncular神經。在正常和GABAB突變鼠中，活化這些神經傳導物質或使用phosphodiesterase抑制劑加強神經傳導，可減少恐懼的反應。作者鑑定出extra-amygdalar circuit和 presynaptic GABAB接受體恐懼上的調控角色。並建議促進神經傳導可減緩恐懼型的疾病。
    Highlights
•Habenula cholinergic neurons reduce fear memory expression
•Presynaptic GABAB activity of habenula neurons facilitates fear extinction
•GABAB drastically potentiates the corelease (co-release) of multiple neurotransmitters
•GABAB amplifies presynaptic Ca2+ entry through Cav2.3 channels
Summary
Fear behaviors are regulated by adaptive mechanisms that dampen their expression in the absence of danger. By studying circuits and the molecular mechanisms underlying this adaptive response, we show that cholinergic neurons of the medial habenula reduce fear memory expression through GABAB presynaptic excitation. Ablating these neurons or inactivating their GABAB receptors impairs fear extinction in mice, whereas activating the neurons or their axonal GABAB receptors reduces conditioned fear. Although considered exclusively inhibitory, here, GABAB mediates excitation by amplifying presynaptic Ca2+ entry through Cav2.3 channels and potentiating co-release of glutamate, acetylcholine, and neurokinin B to excite interpeduncular neurons. Activating the receptors for these neurotransmitters or enhancing neurotransmission with a phosphodiesterase inhibitor reduces fear responses of both wild-type and GABAB mutant mice. We identify the role of an extra-amygdalar circuit and presynaptic GABAB receptors in fear control, suggesting that boosting neurotransmission in this pathway might ameliorate some fear disorders.