Nickerson Poulin Amanda, Guerci Aline, El Mestikawy Salah, Semba Kazue
Department of Anatomy and Neurobiology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada.
J Comp Neurol. 2006 Oct 10;498(5):690-711. doi: 10.1002/cne.21081.
The basal forebrain (BF) plays a role in behavioral and cortical arousal, attention, learning, and memory. It has been suggested that cholinergic BF neurons co-release glutamate, and some cholinergic BF neurons have been reported to contain vesicular glutamate transporter 3 (VGLUT3). We examined the distribution and projections of BF cholinergic neurons containing VGLUT3, by using dual-label immunofluorescence for choline acetyltransferase (ChAT) and VGLUT3, in situ hybridization, and retrograde tracing. Neurons immunoreactive (+) or containing mRNAs for both ChAT and VGLUT3 were mainly localized to the ventral pallidum and more caudal BF regions; the co-immunoreactive neurons represented 31% of cholinergic neurons in the ventral pallidum and 5-9% more caudally. Examination of cholinergic axon terminals in known target areas of BF projections indicated that the basolateral amygdaloid nucleus contained numerous terminals co-immunoreactive for ChAT and VGLUT3, whereas sampled areas of the olfactory bulb, neocortex, hippocampus, reticular thalamic nucleus, and interpeduncular nucleus were devoid of double-labeled terminals. The basolateral amygdala is innervated by cholinergic BF neurons lacking low-affinity p75 nerve growth factor receptors; many ChAT+VGLUT3+ BF neurons were immunonegative to this receptor. Twenty-five to 79% of ChAT+VGLUT3+ neurons in different BF regions were retrogradely labeled from the basolateral amygdala, up to 52% (ventral pallidum) of the retrogradely labeled ChAT+ neurons were VGLUT3+, and the largest number of amygdala-projecting ChAT+VGluT3+ neurons was found in the ventral pallidum. These findings indicate that BF cholinergic neurons containing VGLUT3 project to the basolateral amygdala and suggest that these neurons might have the capacity to release both acetylcholine and glutamate.
基底前脑(BF)在行为和皮层觉醒、注意力、学习及记忆方面发挥作用。有研究表明,胆碱能BF神经元会共同释放谷氨酸,并且有报道称一些胆碱能BF神经元含有囊泡谷氨酸转运体3(VGLUT3)。我们通过使用胆碱乙酰转移酶(ChAT)和VGLUT3的双标免疫荧光、原位杂交及逆行追踪技术,研究了含有VGLUT3的BF胆碱能神经元的分布及投射。ChAT和VGLUT3免疫反应阳性(+)或含有二者mRNA的神经元主要定位于腹侧苍白球及更靠尾侧的BF区域;共免疫反应阳性神经元在腹侧苍白球的胆碱能神经元中占31%,在更靠尾侧的区域占5 - 9%。对BF投射的已知靶区胆碱能轴突终末的检查表明,基底外侧杏仁核含有大量ChAT和VGLUT3共免疫反应阳性的终末,而嗅球、新皮层、海马、丘脑网状核及脚间核的采样区域没有双标终末。基底外侧杏仁核由缺乏低亲和力p75神经生长因子受体的胆碱能BF神经元支配;许多ChAT+VGLUT3+ BF神经元对该受体免疫阴性。不同BF区域中25%至79%的ChAT+VGLUT3+神经元被基底外侧杏仁核逆行标记,逆行标记的ChAT+神经元中高达52%(腹侧苍白球)为VGLUT3+,且在腹侧苍白球中发现投射到杏仁核的ChAT+VGluT3+神经元数量最多。这些发现表明,含有VGLUT3的BF胆碱能神经元投射到基底外侧杏仁核,并提示这些神经元可能有释放乙酰胆碱和谷氨酸的能力。