Electrophysiological characterization of granule cells in the dentate gyrus immediately after birth

Andrea Pedroni,Antonello Mallamaci,Enrico Cherubini,Do Duc Minh

doi:10.3389/fncel.2014.00044

Abstract

Granule cells (GCs) in the dentate gyrus are generated mainly postnatally. Between embryonic day 10 and 14, neural precursors migrate from the primary dentate matrix to the dentate gyrus where they differentiate into neurons. Neurogenesis reaches a peak at the end of the first postnatal week and it is completed at the end of the first postnatal month. This process continues at a reduced rate throughout life. Interestingly, immediately after birth, GCs exhibit a clear GABAergic phenotype. Only later they integrate the classical glutamatergic trisynaptic hippocampal circuit. Here, whole cell patch clamp recordings, in current clamp mode, were performed from immature GCs, intracellularly loaded with biocytin (in hippocampal slices from P0 to P3 old rats) in order to compare their morphological characteristics with their electrophysiological properties. The vast majority of GCs were very immature with small somata, few dendritic branches terminating with small varicosities and growth cones. In spite of their immaturity their axons reached often the cornu ammonis 3 area. Immature GCs generated, upon membrane depolarization, either rudimentary sodium spikes or more clear overshooting action potentials that fired repetitively. They exhibited also low threshold calcium spikes. In addition, most spiking neurons showed spontaneous synchronized network activity, reminiscent of giant depolarizing potentials (GDPs) generated in the hippocampus by the synergistic action of glutamate and GABA, both depolarizing and excitatory. This early synchronized activity, absent during adult neurogenesis, may play a crucial role in the refinement of local neuronal circuits within the developing dentate gyrus.

Highlights

Granule cells (GCs) in the dentate gyrus are crucial for transferring information from the entorhinal cortex to the hippocampus proper where they integrate the classical excitatory trisynaptic circuit (McBain, 2008)
Only a few NeuN-positive cells where found in the coalescing Prox1-positive dentate gyrus, where NeuN co-localized with Prox1
At P6, comparable numbers of Prox1-positive/NeuNnegative and Prox1-positive /NeuN-positive cells were detectable within the inner layer and the outer layer of the granule cell layer (GCL), respectively, at P28, almost all Prox1-positive neurons expressed NeuN, except a few NeuN- elements close to the subgranular zone

Summary

Introduction

Granule cells (GCs) in the dentate gyrus are crucial for transferring information from the entorhinal cortex to the hippocampus proper where they integrate the classical excitatory trisynaptic circuit (McBain, 2008). Immunogold experiments have demonstrated the presence of both AMPA and GABAA receptors, co-localized on MF terminals in close spatial relation with synaptic vesicles (Bergersen et al, 2003). All these pieces of evidence suggest that MF-cornu ammon (CA3) synapses can use GABA as a neurotransmitter since they posses all the machinery for synthesizing, storing, releasing, and sensing it. In line with the sequential formation of GABAergic and glutamatergic synapses in the immature hippocampus (Hennou et al, 2002), GABA appears to be the only neurotransmitter released from MF terminals during the first few days of postnatal life (Kasyanov et al, 2004; Safiulina et al, 2006, 2010; Sivakumaran et al, 2009) while AMPA/kainate receptor mediated synaptic currents start appearing only after postnatal (P) day 3 (Marchal and Mulle, 2004)

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Conclusion