The role of cannabinoids in the neurobiology of sensory gating: A firing rate model study

Zachariou, Margarita; Dissanayake, Dilshani W. N.; Owen, Markus R.; Mason, Rob; Coombes, Stephen

doi:10.1016/j.neucom.2006.10.065

Cited by 6 publications

(7 citation statements)

References 21 publications

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“…As we have shown in a previous study (Zachariou et al. 2007 ) a simple phenomenological model of CB dynamics underlying suppression of inhibition is able to abolish sensory gating in a manner consistent with our experimental findings. Here we improve the previous model by using a more realistic firing rate function instead of a sigmoid, namely the F–I curve of the WB and PR models, as described in the Methods.…”

Section: Resultssupporting

confidence: 92%

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Sensory gating and its modulation by cannabinoids: electrophysiological, computational and mathematical analysis

Zachariou

Dissanayake

Coombes

et al. 2008

Cognitive Neurodynamics

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Gating of sensory information can be assessed using an auditory conditioning-test paradigm which measures the reduction in the auditory evoked response to a test stimulus following an initial conditioning stimulus. Recording brainwaves from specific areas of the brain using multiple electrodes is helpful in the study of the neurobiology of sensory gating. In this paper, we use such technology to investigate the role of cannabinoids in sensory gating in the CA3 region of the rat hippocampus. Our experimental results show that application of the exogenous cannabinoid agonist WIN55,212-2 can abolish sensory gating. We have developed a phenomenological model of cannabinoid dynamics incorporated within a spiking neural network model of CA3 with synaptically interacting pyramidal and basket cells. Direct numerical simulations of this model suggest that the basic mechanism for this effect can be traced to the suppression of inhibition of slow GABA B synapses. Furthermore, by working with a simpler mathematical firing rate model we are able to show the robustness of this mechanism for the abolition of sensory gating.

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Section: Resultssupporting

confidence: 92%

“…For a recent review of the biology and modeling of sensory gating we refer the reader to Zachariou et al. ( 2007 ). The primary purpose of this paper is to extend work on sensory gating to include the effects of CBs.…”

Section: Introductionmentioning

confidence: 99%

Sensory gating and its modulation by cannabinoids: electrophysiological, computational and mathematical analysis

Zachariou

Dissanayake

Coombes

et al. 2008

Cognitive Neurodynamics

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“…Although the pace of research in investigating CB signalling has been accelerating over the past few years, to the best of our knowledge, there are relatively very few theoretical approaches in this particular scientific area [29]–[33]. Currently, all the existing models of eCB dynamics are phenomenological and focus on investigating the CBs role at the network, rather than at the synaptic level.…”

Section: Introductionmentioning

confidence: 99%

“…Our fundamental aim was two-fold: (1) to move beyond the existing phenomenological models of the CB retrograde signalling mechanism at the synaptic level [29]–[33] and construct a realistic biophysical model based on existing experimental observations, and (2) to use the validated model as a framework to explore the main hypothesis that DSI is the result of fine tuning between the pre- and post-synaptic cells' activities. In this paper, we present the development of such a biophysically plausible model of CB retrograde signalling at the synaptic level and investigate how this mediates DSI in hippocampus, a brain region crucial for learning and memory.…”

Section: Introductionmentioning

confidence: 99%

A Biophysical Model of Endocannabinoid-Mediated Short Term Depression in Hippocampal Inhibition

et al. 2013

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Memories are believed to be represented in the synaptic pathways of vastly interconnected networks of neurons. The plasticity of synapses, that is, their strengthening and weakening depending on neuronal activity, is believed to be the basis of learning and establishing memories. An increasing number of studies indicate that endocannabinoids have a widespread action on brain function through modulation of synap–tic transmission and plasticity. Recent experimental studies have characterised the role of endocannabinoids in mediating both short- and long-term synaptic plasticity in various brain regions including the hippocampus, a brain region strongly associated with cognitive functions, such as learning and memory. Here, we present a biophysically plausible model of cannabinoid retrograde signalling at the synaptic level and investigate how this signalling mediates depolarisation induced suppression of inhibition (DSI), a prominent form of short-term synaptic depression in inhibitory transmission in hippocampus. The model successfully captures many of the key characteristics of DSI in the hippocampus, as observed experimentally, with a minimal yet sufficient mathematical description of the major signalling molecules and cascades involved. More specifically, this model serves as a framework to test hypotheses on the factors determining the variability of DSI and investigate under which conditions it can be evoked. The model reveals the frequency and duration bands in which the post-synaptic cell can be sufficiently stimulated to elicit DSI. Moreover, the model provides key insights on how the state of the inhibitory cell modulates DSI according to its firing rate and relative timing to the post-synaptic activation. Thus, it provides concrete suggestions to further investigate experimentally how DSI modulates and is modulated by neuronal activity in the brain. Importantly, this model serves as a stepping stone for future deciphering of the role of endocannabinoids in synaptic transmission as a feedback mechanism both at synaptic and network level.

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“…It is thus generally believed that endocannabinoids are able to affect learning and memorization because of their ability to regulate the potentiation of synaptic connections. In particular, it has been shown that damage of the cannabinoid system (that can be caused by exogenous cannabinoids or by schizophrenia or other mental illnesses) can negatively influence learning and memorization [5,6]. It is thus important to understand how cannabinoids affect neuronal activity.…”

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confidence: 99%

Depolarization Block in the Endocannabinoid System of the Hippocampus

Tirozzi

Londei²,

Gianani³

2020

NeuroSci

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Depolarization block is such a mechanism that the firing activity of a neuronal system is stopped for particular values of the input current. It is important to block epilepsy or unpleasant firing rates. We investigate this property for a non-linear model of CA3 hippocampal neurons under the action of endocannabinoid transmitters. The aim is to discover if they induce depolarization block, a property already seen in other neuronal models and observed in some experiments, signifying that the neural population increases its spiking frequency as some main parameter changes until reaching a situation of no firing. The results is theoretical and it could be useful for investigating real system of neurons of the hippocampus. In some papers it has been shown that this property is connected with bistability, which means that the system has two equilibrium states for some ranges of its parameters. Endocannabinoids influence the learning and memory process and so we concentrate our attention on the CA3 neurons of the hippocampus. We find bistability and depolarization block for the considered model, which is a generalization of the Wilson-Cowan model. The model describes average properties of neurons divided in three classes: the excitatory neuronal population (CA3 neurons) and two types of inhibitory neuron populations (basket cells). The exogenous concentration of cannabinoids is the parameter that controls bistability. This result can be used for an experiment that could give information for medical therapy. We study the time evolution of the synapses connecting the excitatory population with two types of basket cells. The evolution of synaptic weights is considered to be a toy model of the learning process. But this model cannot encompass the complexity and diversity of exogenous and endogenous endocannabinoids effects in vivo.

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The role of cannabinoids in the neurobiology of sensory gating: A firing rate model study

Cited by 6 publications

References 21 publications

Sensory gating and its modulation by cannabinoids: electrophysiological, computational and mathematical analysis

Sensory gating and its modulation by cannabinoids: electrophysiological, computational and mathematical analysis

A Biophysical Model of Endocannabinoid-Mediated Short Term Depression in Hippocampal Inhibition

Depolarization Block in the Endocannabinoid System of the Hippocampus

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