The CAN‐In network: A biologically inspired model for self‐sustained theta oscillations and memory maintenance in the hippocampus

Abstract

During working memory tasks, the hippocampus exhibits synchronous theta-band activity, which is thought to be correlated with the short-term memory maintenance of salient stimuli. Recent studies indicate that the hippocampus contains the necessary circuitry allowing it to generate and sustain theta oscillations without the need of extrinsic drive. However, the cellular and network mechanisms supporting synchronous rhythmic activity are far from being fully understood. Based on electrophysiological recordings from hippocampal pyramidal CA1 cells, we present a possible mechanism for the maintenance of such rhythmic theta-band activity in the isolated hippocampus. Our model network, based on the Hodgkin-Huxley formalism, comprising pyramidal neurons equipped with calcium-activated nonspecific cationic (CAN) ion channels, is able to generate and sustain synchronized theta oscillations (4-12 Hz), following a transient stimulation. The synchronous network activity is maintained by an intrinsic CAN current (I ), in the absence of constant external input. When connecting the pyramidal-CAN network to fast-spiking inhibitory interneurons, the dynamics of the model reveal that feedback inhibition improves the robustness of fast theta oscillations, by tightening the synchronization of the pyramidal CAN neurons. The frequency and power of the theta oscillations are both modulated by the intensity of the I , which allows for a wide range of oscillation rates within the theta band. This biologically plausible mechanism for the maintenance of synchronous theta oscillations in the hippocampus aims at extending the traditional models of septum-driven hippocampal rhythmic activity. © 2017 Wiley Periodicals, Inc.

A detailed anatomical and mathematical model of the hippocampal formation for the generation of sharp-wave ripples and theta-nested gamma oscillations

“…The complete expressions for all these ionic channel currents are detailed in [Giovannini et al, 2017].…”

“…In order to simulate the complete hippocampal formation, our model uses point neural models (single-compartment) but having realistic dynamics (conductance-based Hodgkin-Huxley neurons). Among these neurons, some have one of the membrane channel's conductance directly linked to the level of Ach (CAN, see [Giovannini et al, 2017]). The microscopic anatomy of the neurons was approximated by two compartments (the simplest shape able to generate a relatively realistic LFP through a dipolar electric field [Pettersen et al, 2012]), while the macroscopic anatomy of the hippocampal structure was reproduced by positioning and connecting the neurons in an anatomically realistic manner.…”

Combining theory, model and experiment to understand how theta rhythms are generated in the hippocampus

“…In a very recent study Giovannini et al (2017) focused on the contribution of a non-specific cation (CAN) current in pyramidal cells as critical for the maintenance of theta oscillations in the isolated hippocampus preparation. Interestingly, similar to our work here, they showed that when pyramidal cells were coupled with inhibitory cells, theta oscillations became more robust.…”

The evolving concept of the intrinsic hippocampal theta gamma oscillator

“…This electrophysiological property can be explained considering that the repertoire of ion channels that pyramidal cells express in their dendrites including HCN and Kv7 channels confer them a specific adaptive inductance (119,120). Recently Giovannini et al (2017) (121) showed that a network of pyramidal cell CAN neurons may work as a θ/γ oscillator. More specifically, it can work in three different modes of operation: a slow asynchronous mode, a synchronized θ mode and a synchronized fast γ mode.…”