Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029, USA.
J Neurosci. 2012 May 16;32(20):6957-66. doi: 10.1523/JNEUROSCI.5718-11.2012.
Numerous studies have found that chronic cocaine increases dendritic spine density of medium spiny neurons in the nucleus accumbens (NAc). Here, we used single-cell microinjections and advanced 3D imaging and analysis techniques to extend these findings in several important ways: by assessing cocaine regulation of dendritic spines in the core versus shell subregions of NAc in the mouse, over a broad time course (4 h, 24 h, or 28 d) of withdrawal from chronic cocaine, and with a particular focus on proximal versus distal dendrites. Our data demonstrate subregion-specific, and in some cases opposite, regulation of spines by cocaine on proximal but not distal dendrites. Notably, all observed density changes were attributable to selective regulation of thin spines. At 4 h after injection, the proximal spine density is unchanged in the core but significantly increased in the shell. At 24 h, the density of proximal dendritic spines is reduced in the core but increased in the shell. Such downregulation of thin spines in the core persists through 28 d of withdrawal, whereas the spine density in the shell returns to baseline levels. Consistent with previous results, dendritic tips exhibited upregulation of dendritic spines after 24 h of withdrawal, an effect localized to the shell. The divergence in regulation of proximal spine density in NAc core versus shell by cocaine correlates with recently reported electrophysiological data from a similar drug administration regimen and might represent a key mediator of changes in the reward circuit that drive aspects of addiction.
许多研究发现，慢性可卡因会增加伏隔核（NAc）中中间神经元的树突棘密度。在这里，我们使用单细胞微注射和先进的 3D 成像和分析技术，以几种重要方式扩展了这些发现：通过评估可卡因对慢性可卡因戒断后 4 小时、24 小时或 28 天的 NAc 核心和壳区树突棘的调节作用，以及特别关注近端和远端树突。我们的数据表明，可卡因对近端树突而不是远端树突的棘突具有亚区特异性，在某些情况下甚至具有相反的调节作用。值得注意的是，所有观察到的密度变化都归因于薄棘突的选择性调节。在注射后 4 小时，核心区的近端棘突密度不变，但壳区的近端棘突密度显著增加。在 24 小时时，核心区近端树突棘的密度降低，但壳区的密度增加。这种核心区薄棘突的下调持续到 28 天的戒断期，而壳区的棘突密度恢复到基线水平。与之前的结果一致，在戒断 24 小时后，树突末梢表现出树突棘的上调，这种效应局限于壳区。可卡因对 NAc 核心区和壳区近端棘突密度的调节差异与类似药物给药方案的最近报道的电生理数据相关，并且可能代表驱动成瘾方面变化的奖励回路变化的关键介质。
