Network properties of a computational model of the dorsal raphe nucleus

Wong‐Lin, KongFatt; Joshi, Alok; Prasad, Girijesh; McGinnity, T.M.

doi:10.1016/j.neunet.2012.02.009

Cited by 20 publications

(30 citation statements)

References 39 publications

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“…We found that the computational speed is greatly enhanced for the reduced model. We expect the improvement to be further enhanced in more realistic synaptically coupled neuronal network models (e.g., [12]). …”

Section: Discussionmentioning

confidence: 97%

“…The spiking patterns of these neuronal models depend only on a small set of parameters. To mimic serotonergic neurons, the Izhikevich model parameters were obtained from [12]. In particular, we simulate, under noisy condition, bursting spiking behavior with a higher reset value for the neuronal membrane potential immediately after a spike.…”

Section: Implementation Of Reduced Model With Fast Dynamics In a Smentioning

confidence: 99%

“…We find that the full model takes about 16 h of actual simulation time while the reduced model takes only 4.25 h; about 3.8 times faster. We expect this improved computational speed to be even more significant in synaptically coupled neuronal network models, which are typically much slower due to the simulation of the large connectivity matrices and/or their dynamics (e.g., [12]). More available information regarding the …”

Section: Implementation Of Reduced Model With Fast Dynamics In a Smentioning

confidence: 99%

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Reduced Computational Models of Serotonin Synthesis, Release, and Reuptake

Flower

Wong‐Lin

2014

IEEE Trans. Biomed. Eng.

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Multiscale computational models can provide systemic evaluation and prediction of neuropharmacological drug effects. To date, little computational modeling work has been done to bridge from intracellular to neuronal circuit level. A complex model that describes the intracellular dynamics of the presynaptic terminal of a serotonergic neuron has been previously proposed. By systematically perturbing the model's components, we identify the slow and fast dynamical components of the model, and the reduced slow or fast mode of the model is computationally significantly more efficient with accuracy not deviating much from the original model. The reduced fast-mode model is particularly suitable for incorporating into neurobiologically realistic spiking neuronal models, and hence for large-scale realistic computational simulations. We also develop user-friendly software based on the reduced models to allow scientists to rapidly test and predict neuropharmacological drug effects at a systems level.

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Section: Discussionmentioning

confidence: 97%

Section: Implementation Of Reduced Model With Fast Dynamics In a Smentioning

confidence: 99%

Section: Implementation Of Reduced Model With Fast Dynamics In a Smentioning

confidence: 99%

See 1 more Smart Citation

Reduced Computational Models of Serotonin Synthesis, Release, and Reuptake

Flower

Wong‐Lin

2014

IEEE Trans. Biomed. Eng.

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“…The motivation for this is that it has been known that 5-HT and Ox can phasically activate in the presence of behaviourally relevant stimuli [84], [85], [86]. Furthermore, our current experimental finding suggests that 5-HT can influence LHA neurons over multiple timescales, through both the slow G-protein-coupled (non-5-HT 3A ) and fast ligand-gated (5-HT 3A ) receptors.…”

Section: Resultsmentioning

confidence: 60%

Neural Circuit Interactions between the Dorsal Raphe Nucleus and the Lateral Hypothalamus: An Experimental and Computational Study

et al. 2014

Self Cite

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Orexinergic/hypocretinergic (Ox) neurotransmission plays an important role in regulating sleep, as well as in anxiety and depression, for which the serotonergic (5-HT) system is also involved in. However, little is known regarding the direct and indirect interactions between 5-HT in the dorsal raphe nucleus (DRN) and Ox neurons in the lateral hypothalamus (LHA). In this study, we report the additional presence of 5-HT1BR, 5-HT2AR, 5-HT2CR and fast ligand-gated 5-HT3AR subtypes on the Ox neurons of transgenic Ox-enhanced green fluorescent protein (Ox-EGFP) and wild type C57Bl/6 mice using single and double immunofluorescence (IF) staining, respectively, and quantify the colocalization for each 5-HT receptor subtype. We further reveal the presence of 5-HT3AR and 5-HT1AR on GABAergic neurons in LHA. We also identify NMDAR1, OX1R and OX2R on Ox neurons, but none on adjacent GABAergic neurons. This suggests a one-way relationship between LHA’s GABAergic and Ox neurons, wherein GABAergic neurons exerts an inhibitory effect on Ox neurons under partial DRN’s 5-HT control. We also show that Ox axonal projections receive glutamatergic (PSD-95 immunopositive) and GABAergic (Gephyrin immunopositive) inputs in the DRN. We consider these and other available findings into our computational model to explore possible effects of neural circuit connection types and timescales on the DRN-LHA system’s dynamics. We find that if the connections from 5-HT to LHA’s GABAergic neurons are weakly excitatory or inhibitory, the network exhibits slow oscillations; not observed when the connection is strongly excitatory. Furthermore, if Ox directly excites 5-HT neurons at a fast timescale, phasic Ox activation can lead to an increase in 5-HT activity; no significant effect with slower timescale. Overall, our experimental and computational approaches provide insights towards a more complete understanding of the complex relationship between 5-HT in the DRN and Ox in the LHA.

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“…Additionally, computational models of raph e and other modulatory neurons suggest that their oscillations alter network behavior dramatically at low frequencies (Quilichini and Bernard, 2012). These models present multiple coexisting stable frequencies and spike synchrony that may spread from within a local neural subgroup to the global network (Wong-Lin et al, 2012).…”

Section: Preclinical Evidencementioning

confidence: 99%

Oscillatory serotonin function in depression

Salomon

Cowan

2013

Synapse

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Oscillations in brain activities with periods of minutes to hours may be critical for normal mood behaviors. Ultradian (faster than circadian) rhythms of mood behaviors and associated central nervous system activities are altered in depression. Recent data suggest that ultradian rhythms in serotonin (5HT) function also change in depression. In two separate studies, 5HT metabolites in cerebrospinal fluid (CSF) were measured every 10 m for 24 h before and after chronic antidepressant treatment. Antidepressant treatments were associated with enhanced ultradian amplitudes of CSF metabolite levels. Another study used resting-state functional magnetic resonance imaging (fMRI)to measure amplitudes of dorsal raphé activation cycles following sham or active dietary depletions of the 5HT precursor (tryptophan). During depletion, amplitudes of dorsal raphé activation cycles increased with rapid 6 s periods (about 0.18 Hz)while functional connectivity weakened between dorsal raphé and thalamus at slower periods of 20 s (0.05 Hz). A third approach studied MDMA (ecstasy) users because of their chronically diminished 5HT function compared to non-MDMA polysubstance users (Karageorgiou et al., 2009). Compared to a non-MDMA using cohort, MDMA users showed diminished fMRI intra-regional coherence in motor regions along with altered functional connectivity, again suggesting effects of altered 5HT oscillatory function. These data support a hypothesis that qualities of ultradian oscillations in 5HT function may critically influence moods and behaviors. Dysfunctional 5HT rhythms in depression may be a common endpoint and biomarker for depression, linking dysfunction of slow brain network oscillators to 5HT mechanisms affected by commonly available treatments. 5HT oscillatory dysfunction may define illness subtypes and predict responses to serotonergic agents. Further studies of 5HT oscillations in depression are indicated.

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Network properties of a computational model of the dorsal raphe nucleus

Cited by 20 publications

References 39 publications

Reduced Computational Models of Serotonin Synthesis, Release, and Reuptake

Reduced Computational Models of Serotonin Synthesis, Release, and Reuptake

Neural Circuit Interactions between the Dorsal Raphe Nucleus and the Lateral Hypothalamus: An Experimental and Computational Study

Oscillatory serotonin function in depression

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