Adult-born dentate granule neurons contribute to memory encoding functions of the dentate gyrus (DG) such as pattern separation. However, local circuit-mechanisms by which adult-born neurons partake in this process are poorly understood. Computational, neuroanatomical and electrophysiological studies suggest that sparseness of activation in the granule cell layer (GCL) is conducive for pattern separation. A sparse coding scheme is thought to facilitate the distribution of similar entorhinal inputs across the GCL to decorrelate overlapping representations and minimize interference. Here we used fast voltage-sensitive dye (VSD) imaging combined with laser photostimulation and electrical stimulation to examine how selectively increasing adult DG neurogenesis influences local circuit activity and excitability. We show that DG of mice with more adult-born neurons exhibits decreased strength of neuronal activation and more restricted excitation spread in GCL while maintaining effective output to CA3c. Conversely, blockade of adult hippocampal neurogenesis changed excitability of the DG in the opposite direction. Analysis of GABAergic inhibition onto mature dentate granule neurons in the DG of mice with more adult-born neurons shows a modest readjustment of perisomatic inhibitory synaptic gain without changes in overall inhibitory tone, presynaptic properties or GABAergic innervation pattern. Retroviral labeling of connectivity in mice with more adult-born neurons showed increased number of excitatory synaptic contacts of adult-born neurons onto hilar interneurons. Together, these studies demonstrate that adult hippocampal neurogenesis modifies excitability of mature dentate granule neurons and that this non-cell autonomous effect may be mediated by local circuit mechanisms such as excitatory drive onto hilar interneurons. Modulation of DG excitability by adult-born dentate granule neurons may enhance sparse coding in the GCL to influence pattern separation.
SUMMARY
The neural circuit mechanisms underlying the integration and functions of adult-born dentate granule cell (DGCs) are poorly understood. Adult-born DGCs are thought to compete with mature DGCs for inputs to integrate. Transient genetic overexpression of a negative regulator of dendritic spines, Kruppel-like factor 9 (Klf9), in mature DGCs enhanced integration of adult-born DGCs and increased NSC activation. Reversal of Klf9 overexpression in mature DGCs restored spines, activity, and reset neuronal competition dynamics and NSC activation, leaving the DG modified by a functionally integrated, expanded cohort of age-matched adult-born DGCs. Spine elimination by inducible deletion of Rac1 in mature DGCs increased survival of adult-born DGCs without affecting proliferation or DGC activity. Enhanced integration of adult-born DGCs transiently reorganized adult-born DGC local afferent connectivity and promoted global remapping in the DG. Rejuvenation of the DG by enhancing integration of adult-born DGCs in adulthood, middle age and aging enhanced memory precision.
Memories become less precise and generalize over time as memory traces re-organize in hippocampal-cortical networks. Increased time-dependent loss of memory precision characterizes overgeneralization of fear in post-traumatic stress disorder (PTSD) and age-related cognitive impairments. In the hippocampal dentate gyrus (DG), memories are thought to be encoded by so-called “engram-bearing” dentate granule cells (eDGCs). Here we show using rodents that contextual fear conditioning increases connectivity between eDGCs and inhibitory interneurons in the downstream hippocampal CA3 region. We identify actin-binding LIM protein 3 (abLIM3) as a mossy fiber terminal localized cytoskeletal factor, whose levels decrease upon learning. Downregulation of abLIM3 in DGCs was sufficient to increase connectivity with CA3 stratum lucidum interneurons (SLINs), promote parvalbumin (PV) SLIN activation, enhance feed-forward inhibition onto CA3, and maintain a fear memory engram in the dentate gyrus (DG) over time. Furthermore, abLIM3 downregulation in DGCs conferred conditioned context-specific reactivation of memory traces in hippocampal-cortical and amygdalar networks and decreased fear memory generalization at remote time points. Consistent with age-related hyperactivity of CA3, learning failed to increase DGC-SLIN connectivity in 17 month-old mice, whereas abLIM3 downregulation was sufficient to restore DGC-SLIN connectivity, increase PV-SLIN activation and improve remote memory precision. These studies exemplify a connectivity-based strategy targeting a molecular brake of feedforward inhibition in DG-CA3 that may be harnessed to decrease time-dependent memory generalization in PTSD and improve memory precision in aging.
Soybeans are extensively cultivated worldwide as human food. However, large quantities of soybean roots (SRs), which possess an abundant three-dimensional (3D) structure, remain unused and produce enormous pressure on the environment. Here, 3D hierarchical porous carbon was prepared by the facile carbonization of SRs followed by chemical activation. The as-prepared material, possessing large specific surface area (2143 m g), good electrical conductivity, and unique 3D hierarchical porosity, shows outstanding electrochemical performance as an electrode material for supercapacitors, such as a high capacitance (276 F g at 0.5 A g), superior cycle stability (98% capacitance retention after 10,000 cycles at 5 A g), and good rate capability in a symmetric two-electrode supercapacitor in 6 M KOH. Furthermore, the maximum energy density of as-assembled symmetric supercapacitor can reach 100.5 Wh kg in neat EMIM BF. Moreover, a value of 40.7 Wh kg is maintained at ultrahigh power density (63000 W kg). These results show that the as-assembled supercapacitor can simultaneously deliver superior energy and power density.
Defect‐rich carbon materials possess high gravimetric potassium storage capability due to the abundance of active sites, but their cyclic stability is limited because of the low reversibility of undesirable defects and the deteriorative conductivity. Herein, in situ defect‐selectivity and order‐in‐disorder synergetic engineering in carbon via a self‐template strategy is reported to boost the K+‐storage capacity, rate capability and cyclic stability simultaneously. The defect‐sites are selectively tuned to realize abundant reversible carbon‐vacancies with the sacrifice of poorly reversible heteroatom‐defects through the persistent gas release during pyrolysis. Meanwhile, nanobubbles generated during the pyrolysis serve as self‐templates to induce the surface atom rearrangement, thus in situ embedding nanographitic networks in the defective domains without serious phase separation, which greatly enhances the intrinsic conductivity. The synergetic structure ensures high concentration of reversible carbon‐vacancies and fast charge‐transfer kinetics simultaneously, leading to high reversible capacity (425 mAh g−1 at 0.05 A g−1), high‐rate (237.4 mAh g−1 at 1 A g−1), and superior cyclic stability (90.4% capacity retention from cycle 10 to 400 at 0.1 A g−1). This work provides a rational and facile strategy to realize the tradeoff between defect‐sites and intrinsic conductivity, and gives deep insights into the mechanism of reversible potassium storage.
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