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A model of amygdala function following plastic changes at specific synapses during extinction.

ABSTRACT: The synaptic networks in the amygdala have been the subject of intense interest in recent times, primarily because of the role of this structure in emotion. Fear and its extinction depend on the workings of these networks, with particular interest in extinction because of its potential to ameliorate adverse symptoms associated with post-traumatic stress disorder. Here we place emphasis on the extinction networks revealed by recent techniques, and on the probable plasticity properties of their synaptic connections. We use modules of neurons representing each of the principal components identified as involved in extinction. Each of these modules consists of neural networks, containing specific ratios of excitatory and specialized inhibitory neurons as well as synaptic plasticity mechanisms appropriate for the component of the amygdala they represent. While these models can produce dynamic output, here we concentrate on the equilibrium outputs and do not model the details of the plasticity mechanisms. Pavlovian fear conditioning generates a fear memory in the lateral amygdala module that leads to activation of neurons in the basal nucleus fear module but not in the basal nucleus extinction module. Extinction protocols excite infralimbic medial prefrontal cortex neurons (IL) which in turn excite so-called extinction neurons in the amygdala, leading to the release of endocannabinoids from them and an increase in efficacy of synapses formed by lateral amygdala neurons on them. The model simulations show how such a mechanism could explain experimental observations involving the role of IL as well as endocannabinoids in different temporal phases of extinction.

SUBMITTER: Bennett MR

PROVIDER: S-EPMC6535631 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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A model of amygdala function following plastic changes at specific synapses during extinction.

Bennett Maxwell R MR Farnell Les L Gibson William G WG Lagopoulos Jim J

Neurobiology of stress 20190201

The synaptic networks in the amygdala have been the subject of intense interest in recent times, primarily because of the role of this structure in emotion. Fear and its extinction depend on the workings of these networks, with particular interest in extinction because of its potential to ameliorate adverse symptoms associated with post-traumatic stress disorder. Here we place emphasis on the extinction networks revealed by recent techniques, and on the probable plasticity properties of their sy ...[more]

PMID: 31193487

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Project description:A number of gene expression studies have investigated changes induced by drug exposure, but few reports describe changes that persist following relapse. In this study, genome-wide analysis of gene expression was conducted following an extinction session (90 min) in rats that expressed behavioral incubation of heroin-seeking and goal-directed behavior. As an important modulator of goal-directed behavior, the medial prefrontal cortex (mPFC) was the target of genomic analysis. Rats were trained to self-administer heroin during 3 h daily sessions for 14 d. Following the self-administration period, rats were reintroduced to the self-administration chambers for a 90-minute extinction session in which they could seek heroin, but received none. Extinction sessions were conducted on groups after either 1 d or 14 d of drug-free enforced abstinence to demonstrate behavioral incubation.Behavioral data demonstrated incubation (increased expression) of heroin-seeking and goal-directed behavior after the 14 d abstinent period. That is, following 14 d of enforced abstinence, animals displayed heightened drug-seeking behavior when returned to the environment where they had previously received heroin. This increased drug-seeking took place despite the fact that they received no drug during this extinction session. Whole genome gene expression analysis was performed and results were confirmed by quantitative real-time PCR (RT-qPCR). Microarrays identified 66 genes whose expression was identified as changed by at least 1.4 fold (p < 0.02) following 14 d of abstinence and the 90-minute extinction session compared to the saline treated controls. Orthogonal confirmation by RT-qPCR demonstrated significant alterations in bdnf, calb1, dusp5, dusp6, egr1, npy, rgs2.Ontological analysis indicates that several of the genes confirmed to be changed are important for neuroplasticity, and through that role may impact learning and behavior. The importance of drug-seeking behavior and memory of previous drug-taking sessions suggest that such genes may be important for relapse. The global gene expression analysis adds to the knowledge of heroin-induced changes and further highlights similarities between heroin and other drugs of abuse.

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A model of amygdala function following plastic changes at specific synapses during extinction.

Publications

A model of amygdala function following plastic changes at specific synapses during extinction.

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