A computational study on how theta modulated inhibition can account for the long temporal delays in the entorhinal-hippocampal loop

Cutsuridis, Vassilis and Poirazi, Panayiota (2015) A computational study on how theta modulated inhibition can account for the long temporal delays in the entorhinal-hippocampal loop. Neurobiology of Learning and Memory, 120 . pp. 69-83. ISSN 1074-7427


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A recent experimental study (Mizuseki, Sirota, Pastalkova, & Buzsaki, 2009) has shown that the temporal
delays between population activities in successive entorhinal and hippocampal anatomical stages are
longer (about 70–80 ms) than expected from axon conduction velocities and passive synaptic integration
of feed-forward excitatory inputs. We investigate via computer simulations the mechanisms that give
rise to such long temporal delays in the hippocampus structures. A model of the dentate gyrus (DG),
CA3 and CA1 microcircuits is presented that uses biophysical representations of the major cell types
including granule cells, CA3 and CA1 pyramidal cells (PCs) and six types of interneurons: basket cells
(BCs), axo-axonic cells (AACs), bistratified cells (BSCs), oriens lacunosum-moleculare cells (OLMs), mossy
cells (MCs) and hilar perforant path associated cells (HC). Inputs to the network came from the entorhinal
cortex (EC) (layers 2 and 3) and the medial septum (MS). The model simulates accurately the timing of
firing of different hippocampal cells with respect to the theta rhythm. The model shows that the experimentally
reported long temporal delays in the DG, CA3 and CA1 hippocampal regions are due to theta
modulated somatic and axonic inhibition. The model further predicts that the phase at which the CA1
PCs fire with respect to the theta rhythm is determined primarily by their increased dendritic excitability
caused by the decrease of the axial resistance and the A-type K+ conductance along their dendritic trunk.
The model predicted latencies by which the DG, CA3 and CA1 principal cells fire are inline with the
experimental evidence. Finally, the model proposes functional roles for the different inhibitory interneurons
in the retrieval of the memory pattern by the DG, CA3 and CA1 networks. The model makes a number
of predictions, which can be tested experimentally, thus leading to a better understanding of the
biophysical computations in the hippocampus.

Keywords:Theta oscillation, Computer model, Inhibition, Medial septum, GABA-A, Dentate gyrus, CA3, CA1, NotOAChecked
Subjects:B Subjects allied to Medicine > B140 Neuroscience
G Mathematical and Computer Sciences > G730 Neural Computing
Divisions:College of Science > School of Computer Science
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ID Code:27736
Deposited On:03 Jul 2017 09:29

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