Oscillatory Dynamics of Brain Microcircuits

Skinner, Frances K.; Chatzikalymniou, Alexandra P.

doi:10.1002/9781119159193.ch7

Cited by 2 publications

(2 citation statements)

References 60 publications

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“…A critical difference between the bistable network mechanism of Ho et al (2012) and bistability related to properties of the ING mechanism (analogous to that presented here) was summarized by Skinner and Chatzikalymniou (2017). In the work of Ho et al (2012), the mean excitatory drive received by inhibitory cells in the network must be close to their spiking rheobase.…”

Section: The Relationship Between the "Bistable Transition" Mechanismmentioning

confidence: 79%

Inhibitory Network Bistability Explains Increased Interneuronal Activity Prior to Seizure Onset

Rich

Chameh

Rafiee

et al. 2020

Front. Neural Circuits

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Recent experimental literature has revealed that GABAergic interneurons exhibit increased activity prior to seizure onset, alongside additional evidence that such activity is synchronous and may arise abruptly. These findings have led some to hypothesize that this interneuronal activity may serve a causal role in driving the sudden change in brain activity that heralds seizure onset. However, the mechanisms predisposing an inhibitory network toward increased activity, specifically prior to ictogenesis, without a permanent change to inputs to the system remain unknown. We address this question by comparing simulated inhibitory networks containing control interneurons and networks containing hyperexcitable interneurons modeled to mimic treatment with 4-Aminopyridine (4-AP), an agent commonly used to model seizures in vivo and in vitro. Our in silico study demonstrates that model inhibitory networks with 4-AP interneurons are more prone than their control counterparts to exist in a bistable state in which asynchronously firing networks can abruptly transition into synchrony driven by a brief perturbation. This transition into synchrony brings about a corresponding increase in overall firing rate. We further show that perturbations driving this transition could arise in vivo from background excitatory synaptic activity in the cortex. Thus, we propose that bistability explains the increase in interneuron activity observed experimentally prior to seizure via a transition from incoherent to coherent dynamics. Moreover, bistability explains why inhibitory networks containing hyperexcitable interneurons are more vulnerable to this change in dynamics, and how such networks can undergo a transition without a permanent change in the drive. We note that while our comparisons are between networks of control and ictogenic neurons, the conclusions drawn specifically relate to the unusual dynamics that arise prior to seizure, and not seizure onset itself. However, providing a mechanistic explanation for this phenomenon specifically in a pro-ictogenic setting generates experimentally testable hypotheses regarding the role of inhibitory neurons in pre-ictal neural dynamics, and motivates further computational research into mechanisms underlying a newly hypothesized multi-step pathway to seizure initiated by inhibition.

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Section: The Relationship Between the "Bistable Transition" Mechanismmentioning

confidence: 79%

Inhibitory Network Bistability Explains Increased Interneuronal Activity Prior to Seizure Onset

Rich

Chameh

Rafiee

et al. 2020

Front. Neural Circuits

Self Cite

View full text Add to dashboard Cite

show abstract

“…al. [63] and 684 bistability related to properties of the ING mechanism (analogous to that presented 685 here) was summarized by Skinner and Chatzikalymniou [67]. In the work of Ho et.…”

mentioning

confidence: 61%

Modeling implicates inhibitory network bistability as an underpinning of seizure initiation

Rich

Rafiee

et al. 2019

Preprint

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A plethora of recent experimental literature implicates the abrupt, synchronous activation of GABAergic interneurons in driving the sudden change in brain activity that heralds seizure initiation. However, the mechanisms predisposing an inhibitory network toward sudden coherence specifically during ictogenesis remain unknown. We address this question by comparing simulated inhibitory networks containing control interneurons and networks containing hyper-excitable interneurons modeled to mimic treatment with 4-Aminopyridine (4-AP), an agent commonly used to model seizures in vivo and in vitro. Our in silico study demonstrates that model inhibitory networks with 4-AP interneurons are more prone than their control counterparts to exist in a bistable state in which asynchronously firing networks can abruptly transition into synchrony due to a brief perturbation. We further show that perturbations driving this transition could reasonably arise in vivo based on models of background excitatory synaptic activity in the cortex. Thus, these results propose a mechanism by which an inhibitory network can transition from incoherent to coherent dynamics in a fashion that may precipitate seizure as a downstream effect. Moreover, this mechanism specifically April 11, 2019 1/36Recently, some studies of seizure initiation have shifted focus to over-activity of 25 inhibitory interneurons. This literature has yielded convincing evidence that 26 interneurons serve a causal role in seizure initiation [1,[8][9][10][11][12][13], laying the groundwork for 27 a novel hypothesis for seizure initiation (a "GABAergic initiation hypothesis") in which 28 synchronous activation of inhibitory interneurons precipitates the onset of a seizure, as 29 diagrammed in Fig 1 [12]. Given the contemporaneous nature of this hypothesis it is an 30ideal target for rigorous computational study; here, such research aims to unearth a 31 mechanism explaining the predisposition of inhibitory interneurons in a hyper-excitable 32April 11, 2019 2/36 environment to suddenly transition into synchrony, the necessary initial step in this 33 hypothesis. We thus focus on the earliest time in the transition to seizure and not 34 aspects of propagation and termination. 35The study of inhibitory network synchrony is decades old, dating back to the work of 36 Wang and Rinzel [14]. Various mechanisms have been proposed to explain the 37 generation of oscillations in purely inhibitory networks, the most prominent of which 38 may be the Interneuron Network Gamma (ING) mechanism [15-20]. Previous work has 39 shown that inhibitory networks built to examine population activity in an in vitro 40 hippocampal preparation manifest "sharp transitions" into coherent population activity 41 caused by a small, permanent increase to the external drive to the network [21]. 42 Additional studies have explored the effect of connection probabilities and cell 43 characteristics manifested by classifications of cell excitability on inhibitory network 44 synchrony [22, 23], and have noted that bist...

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Oscillatory Dynamics of Brain Microcircuits

Cited by 2 publications

References 60 publications

Inhibitory Network Bistability Explains Increased Interneuronal Activity Prior to Seizure Onset

Inhibitory Network Bistability Explains Increased Interneuronal Activity Prior to Seizure Onset

Modeling implicates inhibitory network bistability as an underpinning of seizure initiation

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