Harkany Tibor, Mackie Ken, Doherty Patrick
Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Scheeles väg 1 :A1, Karolinska Institute, SE-17177 Stockholm, Sweden.
Curr Opin Neurobiol. 2008 Jun;18(3):338-45. doi: 10.1016/j.conb.2008.08.007.
Endocannabinoids (eCBs) function as retrograde messengers at both excitatory and inhibitory synapses, and control various forms of synaptic plasticity in the adult brain. The molecular machinery required for specific eCB functions during synaptic plasticity is well established. However, eCB signaling plays surprisingly fundamental roles in controlling the acquisition of neuronal identity during CNS development. Recent work suggests that selective recruitment of regulatory signaling networks to CB1 cannabinoid receptors dictates neuronal state-change decisions. In addition, the spatial localization and temporal precision of eCB actions emerges as a novel organizer in developing neuronal networks. Current challenges include fitting novel molecular candidates into regulatory eCB signaling pathways, and defining the temporal dynamics of context-dependent signaling mechanisms underpinning particular neuronal specification events.
内源性大麻素(eCBs)在兴奋性和抑制性突触中均作为逆行信使发挥作用,并控制成人大脑中各种形式的突触可塑性。突触可塑性过程中特定eCB功能所需的分子机制已得到充分确立。然而,eCB信号传导在中枢神经系统发育过程中控制神经元特性的获得方面发挥着令人惊讶的重要作用。最近的研究表明,将调节信号网络选择性招募到CB1大麻素受体决定了神经元状态改变的决策。此外,eCB作用的空间定位和时间精度成为发育中神经网络的一种新型组织者。当前的挑战包括将新的分子候选物纳入调节性eCB信号通路,以及确定支持特定神经元特化事件的上下文依赖性信号机制的时间动态。