A consistent electrophysiological model of dentate granule cells based on pharmacology to study adult-born neurons

BEINING M; MONGIAT LA; CUNTZ H; JEDLIKA P

Chicago

Congreso; Society for Neurosciences; 2015

Society for Neurosciences

Granule cells in the dentate gyrus (DGCs) are continuously generated in the adult mammal brain. Their integration into the hippocampal network has been linked to important brain functions such as pattern separation and spatial memory formation.Interestingly, DGCs show a critical time window, in which they express higher excitability, synaptic plasticity and excitation-to-inhibition ratio, each phenomenon linked to specific protein expression or connectivity. A data-driven single-cell compartmental model with realistic morphology and ion channel composition would provide an excellent tool to analyze the effect of all these changes in intrinsicand synaptic properties on neuronal computation. However, existing active compartmental models of DGCs have limited predictive capability since they were constructed ad hoc in order to replicate mostly one single experiment. Here we present a novel active model for mature DGCs based on raw electrophysiological traces combined with pharmacology in mice (1). Our new model includes a corrected calcium buffer model, an inward rectifier potassium (Kir) channel, several isoforms of voltage-gated potassium channels and modified distributions of BK, SK as well as L-, T-, N-type calcium channels, consistent with the known DGC ion channel composition. The resulting model reproduces experimental electrophysiology in mature DGCs. Furthermore, the calcium dynamics, as well as spiking characteristics such as afterhyperpolarization, depolarizing afterpotential and spiking adaption are in a realistic rangeindicating that the DGC compartmental model is consistent across a variety of experimental paradigms. The model can now be adapted tosimulate synaptic integration and plasticity in adult-born DGCs. Our preliminary simulations suggest, that NMDA subunit composition alone might not suffice to fully explain the increased capability for synaptic plasticity during the critical time window (2). In summary, we created a novel active DGC compartmental model, which is consistent in ion channel composition and electrophysiology, enabling us to make valuable predictions about single-cell computation in mature and adult-born DGCs. 1) L. Mongiat, M. S. Espósito, G. Lombardi, A. F. Schinder, PLoS One. 4, e5320 (2009). 2) S. Ge, C.-H. Yang,K.-S. Hsu, G.-L. Ming, H. Song, Neuron. 54,559-66(2007).