Establishing a combined optogenetic-electrophysiological method to characterize the activity of granule cells in the dentate gyrus of freely moving mice

Efforts to understand the role of the dentate gyrus have been hampered by the limitation of extracellular recordings to identify cell types. By combining extracellular recording with optogenetics, it has become possible to identify and characterize the activity of specific cell types. Here, we assessed the feasibility of this technique to identify granule cells of the dentate gyrus in freely behaving mice. We were able to detect units that responded to light stimulation with short latency and high reliability. Although the short latency suggested that units were directly activated by light stimulation, we could not exclude the possibility that they were indirectly activated postsynaptic neurons. We also detected voltage fluctuations after the light stimulus, which were presumably caused by photovoltaic artefacts and synchronous activation of multiple cells. We believe that optogenetic identification of granule cells could be a valuable technique provided that the uncertainty about the response latency is resolved.​Doctor of Philosophy (SBS

Biofunctional scaffolds with high packing density of aligned electrospun fibers support neural regeneration

Neurons of the central nervous system do not regenerate spontaneously after injury. As such, biofunctional tissue scaffolds have been explored to provide a growth‐promoting environment to enhance neural regeneration. In this regard, aligned electrospun fibers have proven invaluable for regeneration by offering guidance for axons to cross the injury site. However, a high fiber density could potentially limit axonal ingrowth into the scaffold. Here, we explore which fiber density provides the optimal environment for neurons to regenerate. By changing fiber electrospinning time, we generated scaffolds with different fiber densities and implanted these in a rat model of spinal cord injury (SCI). We found that neurons were able to grow efficiently into scaffolds with high fiber density, even if the gaps between fiber bundles were very small (<1 μm). Scaffolds with high fiber density showed good host‐implant integration. Cell infiltration was not affected by fiber density. Efficient blood vessel ingrowth likely requires larger gaps between fibers or faster degrading fibers. We conclude that scaffolds with high fiber densities, and thus a large number of small gaps in between fiber bundles, provide the preferred environment for nerve regeneration after SCI.National Medical Research Council (NMRC)National Research Foundation (NRF)Accepted versionPartial funding support from the Singapore National Research Foundation under its NMRC-CBRG grant (NMRC/CBRG/0096/2015) and administered by the Singapore Ministry of Health’s National Medical Research Council and RRIS Rehabilitation Research Grant (RRG1/16004) are acknowledged

Test, rinse, repeat: A review of carryover effects in rodent behavioral assays

10.1016/j.neubiorev.2022.104560NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS13

Role of NMDA receptors in adult neurogenesis and normal development of the dentate gyrus

The NMDA receptors are a type of glutamate receptors, which is involved in neuronal function, plasticity and development in the mammalian brain. However, how the NMDA receptors contribute to adult neurogenesis and development of the dentate gyrus is unclear. In this study, we investigate this question by examining a region-specific knock-out mouse line that lacks the NR1 gene, which encodes the essential subunit of the NMDA receptors, in granule cells of the dentate gyrus (DG-NR1KO mice). We found that the survival of newly-generated granule cells, cell proliferation and the size of the granule cell layer are significantly reduced in the dorsal dentate gyrus of adult DG-NR1KO mice. Our results also show a significant reduction in the number of immature neurons and in the volume of the granule cell layer, starting from three weeks of postnatal age. DG-NR1KO mice also showed impairment in the expression of an immediate early gene, Arc, and behavior during the novelty-suppressed feeding and open field test. These results suggest that the NMDA receptors in granule cells have a role in adult neurogenesis in the adult brain and contributes to the normal development of the dentate gyrus

Role of NMDA Receptors in Adult Neurogenesis and Normal Development of the Dentate Gyrus

10.1523/eneuro.0566-20.2021eneuro84ENEURO.0566-20.202