کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6271514 | 1614766 | 2015 | 17 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Anatomical evidence for a non-synaptic influence of the K+-dependent Na+/Ca2+-exchanger, NCKX2, on hippocampal plasticity Anatomical evidence for a non-synaptic influence of the K+-dependent Na+/Ca2+-exchanger, NCKX2, on hippocampal plasticity](/preview/png/6271514.png)
- NCKX2 in the hippocampus was localized using immunofluorescent and immunoelectron microscopy.
- Most NCKX2 is found on small oblique dendrites in the CA1 stratum radiatum.
- Some NCKX2 is located on cytoplasmic vesicles and axon terminals in the molecular layer.
- There is variation in the location of NCKX2 in different brain regions.
- NCKX2 maintains normal plasticity in CA1 neurons via an influence on dendritic integration.
The K+-dependent Na+/Ca2-exchanger (NCKX) family is encoded by five related genes, of which NCKX2 (solute carrier family 24, member 2) is the most abundant member present in the brain. Nckx2 knockout mice display profound loss of hippocampal long-term potentiation, and selective deficits in motor learning and spatial working memory. However, the molecular mechanisms underlying these changes have not been established. Thus, the overall goal of this project was to identify the exact subcellular localization of NCKX2 in the hippocampus, as an important step toward understanding the physiological role for NCKX2 in neuronal plasticity. To achieve this goal, we used dual immunofluorescent confocal microscopy and immunoelectron microscopy. Our data demonstrate that the majority of NCKX2 is co-localized with the dendritic marker, microtubule associated protein 2. A smaller fraction is co-localized with the presynaptic marker, synapsin 1, and the smallest amount is co-localized with the glutamatergic spine marker, N-methyl-d-aspartate receptor 1. The data from immunoelectron microscopy are consistent with the observations from dual immunofluorescence, and show that the highest fraction of NCKX2 is located on the plasma membrane of small oblique dendrites, particularly in CA1 neurons of the stratum radiatum. In the molecular layer, a greater fraction of NCKX2 is associated with axon terminals and, in addition, a fraction of NCKX2 is found not associated with the plasma membrane but located in the cytoplasm. These studies describe for the first time the exact location of NCKX2 in the hippocampus of adult mice and suggest that the function of NCKX2 in neuronal plasticity in hippocampal CA1 neurons may be mediated by its kinetic effect on the local Ca2+ concentration that influences dendritic integration. At other hippocampal locations NCKX2 has a somewhat different spatial distribution, consistent with published reports of NCKX2 expression in other brain regions, suggesting that NCKX2 contributes to Ca2+ homeostasis in distinct ways in different brain neurons.
Journal: Neuroscience - Volume 310, 3 December 2015, Pages 372-388