Connectivity and synaptic features of hilar mossy cells and their effects on granule cell activity along the hippocampal longitudinal axis

• Published in: The Journal of physiology 2022-07, Vol.600 (14), p.3355-3381
• Main Authors: Abdulmajeed, Wahab Imam, Wang, Kai‐Yi, Wu, Jei‐Wei, Ajibola, Musa Iyiola, Cheng, Irene Han‐Juo, Lien, Cheng‐Chang
• Format: Article
• Language: English
• Subjects: Channelrhodopsins; Dentate gyrus; Dentate Gyrus - physiology; electrophysiology; GABA; Glutamatergic transmission; Granule cells; Hippocampus; Hippocampus - physiology; Humans; inetrneuron; Information processing; Interneurons; mossy cell; Mossy Fibers, Hippocampal - physiology; Neural networks; optogenetics; synapse
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/JP282804

The hippocampus is an elongated brain structure which runs along a ventral‐to‐dorsal axis in rodents, corresponding to the anterior‐to‐posterior axis in humans. A glutamatergic cell type in the dentate gyrus (DG), the mossy cells (MCs), establishes extensive excitatory collateral connections with the DG principal cells, the granule cells (GCs), and inhibitory interneurons in both hippocampal hemispheres along the longitudinal axis. Although coupling of two physically separated GC populations via long‐axis projecting MCs is instrumental for information processing, the connectivity and synaptic features of MCs along the longitudinal axis are poorly defined. Here, using channelrhodopsin‐2 assisted circuit mapping, we showed that MC excitation results in a low synaptic excitation–inhibition (E/I) balance in the intralamellar (local) GCs, but a high synaptic E/I balance in the translamellar (distant) ones. In agreement with the differential E/I balance along the ventrodorsal axis, activation of MCs either enhances or suppresses the local GC response to the cortical input, but primarily promotes the distant GC activation. Moreover, activation of MCs enhances the spike timing precision of the local GCs, but not that of the distant ones. Collectively, these findings suggest that MCs differentially regulate the local and distant GC activity through distinct synaptic mechanisms. Key points Hippocampal mossy cell (MC) pathways differentially regulate granule cell (GC) activity along the longitudinal axis. MCs mediate a low excitation–inhibition balance in intralamellar (local) GCs, but a high excitation–inhibition balance in translamellar (distant) GCs. MCs enhance the spiking precision of local GCs, but not distant GCs. MCs either promote or suppress local GC activity, but primarily promote distant GC activation. legend figure Hilar mossy cell (MC) pathways differentially innervate dentate granule cells (GCs) and interneurons along the hippocampal longitudinal axis. They mediate a low excitation–inhibition (E/I) balance in intralamellar GCs, but a high E/I balance in translamellar GCs. Notably, optogenetic excitation of MCs enhances the spike timing precision of intralamellar GCs, but not translamellar GCs. Moreover, MC excitation either promotes or suppresses intralamellar GC activity depending on its timing, but primarily promotes translamellar GC activation. Taken together, MCs differentially regulate GC spike timing precision and response to cortical input in a