Berghuis Paul, Dobszay Marton B, Ibanez Raquel Martin, Ernfors Patrik, Harkany Tibor
Department of Medical Biochemistry and Biophysics, Laboratory for Molecular Neurobiology, Scheeles väg 1:A1, Karolinska Institutet, S-17177 Stockholm, Sweden.
Int J Dev Neurosci. 2004 Nov;22(7):533-43. doi: 10.1016/j.ijdevneu.2004.07.012.
The amazing morphological and electrophysiological diversity of cortical GABAergic interneurons subserves the broad diversity of processes these cells modulate in neuronal networks. Until recently, interneuron development and functions have been extensively studied in heterogeneous in vitro and in vivo systems containing both excitatory and inhibitory components. However, mechanisms of interneuron specification during development, key signaling mechanisms controlling the establishment of particular inhibitory neuron subsets, and the spatial and temporal regulation of their integration in neuronal microcircuits remain poorly understood. Selective isolation of particular interneuron subsets may significantly extend our knowledge on the scenario of neurochemical and electrophysiological specification of developing interneurons, identification of signaling cues directing their axon growth, and principles of their anterograde and retrograde synaptic communication with other cell types. Here, we show that selective isolation of perisomatic inhibitory cells containing either parvalbumin or cholecystokinin reveals major differences in the temporal dynamics of their functional differentiation, and their dependence on target-derived signals like brain-derived neurotrophic factor and endocannabinoids. In addition, we discuss therapeutic prospects of modulating increased excitatory output in the hippocampus and subthalamic nucleus by re-adjusting the inhibitory control of principal cells.
皮质GABA能中间神经元惊人的形态和电生理多样性，为这些细胞在神经网络中调节的广泛多样的过程提供了支持。直到最近，中间神经元的发育和功能在包含兴奋性和抑制性成分的异质体外和体内系统中得到了广泛研究。然而，发育过程中中间神经元特化的机制、控制特定抑制性神经元亚群建立的关键信号机制，以及它们在神经元微回路中整合的时空调节，仍然知之甚少。特定中间神经元亚群的选择性分离，可能会显著扩展我们对发育中中间神经元的神经化学和电生理特化情况、指导其轴突生长的信号线索识别，以及它们与其他细胞类型顺行和逆行突触通讯原理的认识。在这里，我们表明，对含有小白蛋白或胆囊收缩素的躯体周围抑制性细胞进行选择性分离，揭示了它们功能分化时间动态的主要差异，以及它们对脑源性神经营养因子和内源性大麻素等靶源性信号的依赖性。此外，我们还讨论了通过重新调整主细胞的抑制控制来调节海马体和丘脑底核中兴奋性输出增加的治疗前景。
