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Dendritic morphology and inhibitory regulation distinguish dentate semilunar granule cells from granule cells through distinct stages of postnatal development

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Semilunar granule cells (SGCs) have been proposed as a morpho-functionally distinct class of hippocampal dentate projection neurons contributing to feedback inhibition and memory processing in juvenile rats. However, the structural and physiological features that can reliably classify granule cells (GCs) from SGCs through postnatal development remain unresolved. Focusing on postnatal days 11–13, 28–42, and > 120, corresponding with human infancy, adolescence, and adulthood, we examined the somato-dendritic morphology and inhibitory regulation in SGCs and GCs to determine the cell-type specific features. Unsupervised cluster analysis confirmed that morphological features reliably distinguish SGCs from GCs irrespective of animal age. SGCs maintain higher spontaneous inhibitory postsynaptic current (sIPSC) frequency than GCs from infancy through adulthood. Although sIPSC frequency in SGCs was particularly enhanced during adolescence, sIPSC amplitude and cumulative charge transfer declined from infancy to adulthood and were not different between GCs and SGCs. Extrasynaptic GABA current amplitude peaked in adolescence in both cell types and was significantly greater in SGCs than in GCs only during adolescence. Although GC input resistance was higher than in SGCs during infancy and adolescence, input resistance decreased with developmental age in GCs, while it progressively increased in SGCs. Consequently, GCs’ input resistance was significantly lower than SGCs in adults. The data delineate the structural features that can reliably distinguish GCs from SGCs through development. The results reveal developmental differences in passive membrane properties and steady-state inhibition between GCs and SGCs which could confound their use in classifying the cell types.

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All reconstructions will be uploaded to Physiology data will be shared upon request.

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Standard software packages, Neurolucida 360, pClamp10 and R were used in analysis. Custom IGOR-Pro code for IPSC analysis will be made available upon request.


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We thank Dr. Luke Fritzky at the Rutgers Imaging Core for help with imaging and Dipika Sekhar for data entry. We thank Drs. Deepak Subramanian and Kelly A. Hamilton for thoughtful discussions and comments.


The project was supported by National Institutes of Health/National Institute of Neurological Diseases and Stroke R01 NS069861, R01NS097750 and New Jersey Commission on Brain Injury Research CBIR16IRG017 to V.S. and, CBIR11FEL003 to A.G

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AG, JG, and AP performed experiments; AG, Y-JC, YS, and VR analyzed data; AG, FSE, and VS interpreted results of experiments; AG and AP prepared figures; AG and VS conceived of and designed research; AG and VS drafted manuscript.

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Correspondence to Vijayalakshmi Santhakumar.

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Gupta, A., Proddutur, A., Chang, YJ. et al. Dendritic morphology and inhibitory regulation distinguish dentate semilunar granule cells from granule cells through distinct stages of postnatal development. Brain Struct Funct 225, 2841–2855 (2020).

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