Interactions between Inhibitory Interneurons and Excitatory Associational Circuitry in Determining Spatio-Temporal Dynamics of Hippocampal Dentate Granule Cells: A Large-Scale Computational Study.

Phillip J Hendrickson,Theodore W Berger,Gene J Yu,Dong Song

doi:10.3389/fnsys.2015.00155

Phillip J Hendrickson, Theodore W Berger + Show 2 more

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https://doi.org/10.3389/fnsys.2015.00155

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Abstract

This paper reports on findings from a million-cell granule cell model of the rat dentate gyrus that was used to explore the contributions of local interneuronal and associational circuits to network-level activity. The model contains experimentally derived morphological parameters for granule cells, which each contain approximately 200 compartments, and biophysical parameters for granule cells, basket cells, and mossy cells that were based both on electrophysiological data and previously published models. Synaptic input to cells in the model consisted of glutamatergic AMPA-like EPSPs and GABAergic-like IPSPs from excitatory and inhibitory neurons, respectively. The main source of input to the model was from layer II entorhinal cortical neurons. Network connectivity was constrained by the topography of the system, and was derived from axonal transport studies, which provided details about the spatial spread of axonal terminal fields, as well as how subregions of the medial and lateral entorhinal cortices project to subregions of the dentate gyrus. Results of this study show that strong feedback inhibition from the basket cell population can cause high-frequency rhythmicity in granule cells, while the strength of feedforward inhibition serves to scale the total amount of granule cell activity. Results furthermore show that the topography of local interneuronal circuits can have just as strong an impact on the development of spatio-temporal clusters in the granule cell population as the perforant path topography does, both sharpening existing clusters and introducing new ones with a greater spatial extent. Finally, results show that the interactions between the inhibitory and associational loops can cause high frequency oscillations that are modulated by a low-frequency oscillatory signal. These results serve to further illustrate the importance of topographical constraints on a global signal processing feature of a neural network, while also illustrating how rich spatio-temporal and oscillatory dynamics can evolve from a relatively small number of interacting local circuits.

Highlights

We recently reported on the first generation of a large-scale, biologically realistic compartmental neuron model of the rat hippocampal dentate gyrus (Hendrickson et al, 2015)
The dentate model consisted of granule cells, basket cells, and mossy cells with input arriving from axons organized as those from layer II neurons of the entorhinal cortex (EC)
Initial simulations of granule cell network dynamics to EC input involved both medial and lateral entorhinal (MEC and lateral entorhinal cortex (LEC)) neurons firing in a Poisson fashion with a mean frequency of 3.0 Hz, slowly accelerated from 0.0 Hz over the course of the first 1,000 ms of the simulation

Summary

Introduction

We recently reported on the first generation of a large-scale, biologically realistic compartmental neuron model of the rat hippocampal dentate gyrus (Hendrickson et al, 2015). This model included one million granule cells, axons from 112 k entorhinal cortical neurons (layer II), and 6 k inhibitory interneurons configured synaptically as basket cells of the dentate gyrus. Associational fibers arise from neurons ipsilateral to a given hemisphere (Zimmer, 1971); commissural fibers arise from contralateral sites (Gottlieb and Cowan, 1973) Both associational and commissural fibers arise from the same cells of origin within the dentate hilus, namely, mossy cells (though other hilar neurons may contribute) (Swanson et al, 1981; Ribak et al, 1985). Mossy cells are distributed loosely within the hilus in the rat, but are located more compactly in the polymorphic layer of the rabbit and other species that are higher on the phylogenetic scale, and that have a more well-organized hilar region (Berger et al, 1981; Amaral et al, 2007)

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