Thomas Deepthi, Recabal-Beyer Antonia, Senecal Joanne Mm, Serletis Demitre, Lynn Bruce D, Jackson Michael F, Nagy James I
Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba Winnipeg, Manitoba, Canada.
Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción Víctor Lamas 1290, Casilla 160, Concepción, Chile.
Int J Physiol Pathophysiol Pharmacol. 2024 Jun 15;16(3):28-54. doi: 10.62347/RTMH4490. eCollection 2024.
Granule cells in the hippocampus project axons to hippocampal CA3 pyramidal cells where they form large mossy fiber terminals. We have reported that these terminals contain the gap junction protein connexin36 (Cx36) specifically in the stratum lucidum of rat ventral hippocampus, thus creating morphologically mixed synapses that have the potential for dual chemical/electrical transmission.
Here, we used various approaches to characterize molecular and electrophysiological relationships between the Cx36-containing gap junctions at mossy fiber terminals and their postsynaptic elements and to examine molecular relationships at mixed synapses in the brainstem.
In rat and human ventral hippocampus, many of these terminals, identified by their selective expression of vesicular zinc transporter-3 (ZnT3), displayed multiple, immunofluorescent Cx36-puncta representing gap junctions, which were absent at mossy fiber terminals in the dorsal hippocampus. In rat, these were found in close proximity to the protein constituents of adherens junctions (i.e., N-cadherin and nectin-1) that are structural hallmarks of mossy fiber terminals, linking these terminals to the dendritic shafts of CA3 pyramidal cells, thus indicating the loci of gap junctions at these contacts. Cx36-puncta were also associated with adherens junctions at mixed synapses in the brainstem, supporting emerging views of the structural organization of the adherens junction-neuronal gap junction complex. Electrophysiologically induced long-term potentiation (LTP) of field responses evoked by mossy fiber stimulation was greater in the ventral than dorsal hippocampus.
The electrical component of transmission at mossy fiber terminals may contribute to enhanced LTP responses in the ventral hippocampus.
海马体中的颗粒细胞将轴突投射至海马体CA3锥体细胞，在那里形成大型苔藓纤维终末。我们曾报道，这些终末在大鼠腹侧海马体的透明层中特异性地含有缝隙连接蛋白连接蛋白36（Cx36），从而形成了具有化学/电双重传递潜力的形态学混合突触。
在此，我们采用多种方法来表征苔藓纤维终末含Cx36的缝隙连接与其突触后元件之间的分子和电生理关系，并研究脑干中混合突触处的分子关系。
在大鼠和人类腹侧海马体中，许多通过囊泡锌转运体-3（ZnT3）的选择性表达鉴定出的这些终末，显示出多个代表缝隙连接的免疫荧光Cx36斑点，而在背侧海马体的苔藓纤维终末中则不存在。在大鼠中，这些斑点靠近黏附连接的蛋白质成分（即N-钙黏蛋白和nectin-1），黏附连接是苔藓纤维终末的结构标志，将这些终末与CA3锥体细胞的树突轴相连，从而表明这些接触处缝隙连接的位置。Cx36斑点也与脑干混合突触处的黏附连接相关，支持了黏附连接-神经元缝隙连接复合体结构组织的新观点。苔藓纤维刺激诱发的场反应的电生理诱导长时程增强（LTP）在腹侧海马体中比背侧海马体中更大。
苔藓纤维终末传递的电成分可能有助于腹侧海马体中增强的LTP反应。
