Models that contain the Region : Brainstem

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    Models   Description
1.  A cortico-cerebello-thalamo-cortical loop model under essential tremor (Zhang & Santaniello 2019)
We investigated the origins of oscillations under essential tremor (ET) by building a computational model of the cortico-cerebello-thalamo-cortical loop. It showed that an alteration of amplitudes and decay times of the GABAergic currents to the dentate nucleus can facilitate sustained oscillatory activity at tremor frequency throughout the network as well as a robust bursting activity in the thalamus, which is consistent with observations of thalamic tremor cells in ET patients. Tremor-related oscillations initiated in small neural populations and spread to a larger network as the synaptic dysfunction increased, while thalamic high-frequency stimulation suppressed tremor-related activity in thalamus but increased the oscillation frequency in the olivocerebellar loop.
2.  Borderline Personality Disorder (Berdahl, 2010)
This research developed a neural network simulation constrained by known neuroanatomy and neurophysiology to generate ideas about the etiology of Borderline Personality Disorder. The simulations suggest an important role for the amygdala-ventromedial prefrontal cortex-amygdala circuit.
3.  Brainstem circuits controlling locomotor frequency and gait (Ausborn et al 2019)
"A series of recent studies identified key structures in the mesencephalic locomotor region and the caudal brainstem of mice involved in the initiation and control of slow (exploratory) and fast (escape-type) locomotion and gait. However, the interactions of these brainstem centers with each other and with the spinal locomotor circuits are poorly understood. Previously we suggested that commissural and long propriospinal interneurons are the main targets for brainstem inputs adjusting gait (Danner et al., 2017). Here, by extending our previous model, we propose a connectome of the brainstem-spinal circuitry and suggest a mechanistic explanation of the operation of brainstem structures and their roles in controlling speed and gait. We suggest that brainstem control of locomotion is mediated by two pathways, one controlling locomotor speed via connections to rhythm generating circuits in the spinal cord and the other providing gait control by targeting commissural and long propriospinal interneurons."
4.  Core respiratory network organization: Insights from optogenetics and modeling (Ausborn et al 2018)
"The circuit organization within the mammalian brainstem respiratory network, specifically within and between the pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes, and the roles of these circuits in respiratory pattern generation are continuously debated. We address these issues with a combination of optogenetic experiments and modeling studies. We used transgenic mice expressing channelrhodopsin-2 under the VGAT-promoter to investigate perturbations of respiratory circuit activity by site-specific photostimulation of inhibitory neurons within the pre-BötC or BötC. The stimulation effects were dependent on the intensity and phase of the photostimulation. Specifically: (1) Low intensity (= 1.0 mW) pulses delivered to the pre-BötC during inspiration did not terminate activity, whereas stronger stimulations (= 2.0 mW) terminated inspiration. (2) When the pre-BötC stimulation ended in or was applied during expiration, rebound activation of inspiration occurred after a fixed latency. (3) Relatively weak sustained stimulation (20 Hz, 0.5–2.0 mW) of pre-BötC inhibitory neurons increased respiratory frequency, while a further increase of stimulus intensity (> 3.0 mW) reduced frequency and finally (= 5.0 mW) terminated respiratory oscillations. (4) Single pulses (0.2–5.0 s) applied to the BötC inhibited rhythmic activity for the duration of the stimulation. (5) Sustained stimulation (20 Hz, 0.5–3.0 mW) of the BötC reduced respiratory frequency and finally led to apnea. We have revised our computational model of pre-BötC and BötC microcircuits by incorporating an additional population of post-inspiratory inhibitory neurons in the pre-BötC that interacts with other neurons in the network. This model was able to reproduce the above experimental findings as well as previously published results of optogenetic activation of pre-BötC or BötC neurons obtained by other laboratories. The proposed organization of pre-BötC and BötC circuits leads to testable predictions about their specific roles in respiratory pattern generation and provides important insights into key circuit interactions operating within brainstem respiratory networks."
5.  Dipolar extracellular potentials generated by axonal projections (McColgan et al 2017)
" ... Here, we established experimentally and theoretically that contributions of axons to EFPs can be significant. Modeling action potentials propagating along axons, we showed that EFPs were prominent in the presence of terminal zones where axons branch and terminate in close succession, as found in many brain regions. Our models predicted a dipolar far field and a polarity reversal at the center of the terminal zone. ..."
6.  Dopamine neuron of the vent. periaqu. gray and dors. raphe nucleus (vlPAG/DRN) (Dougalis et al 2017)
The following computer model describes the electrophysiological properties of dopamine (DA) neurons of the ventrolateral periaquaductal gray and dorsal raphe nucleus (vlPAG/DRN). the model and how to replicate Figures 7-10 of the manuscript (Dougalis et al., 2017 J Comput Neurosci). SUMMARY: We have conducted a voltage-clamp study to provide a kinetic description of major sodium, potassium and calcium ionic currents operant on adult DA vlPAG/DRN neurons in brain slices obtained from pitx3-GFP mice. Based on experimentally derived voltage-clamp data, we then constructed a simplified, conductance-based, Hodgkin and Huxley-type, computer model and validated its behaviour against in vitro neurophysiological data. Using simulations in the computational DA model, we explored the contribution of individual ionic currents in vlPAG/DRN DA neuron’s spontaneous firing, pacemaker frequency and threshold for spike frequency adaptation in silico. The data presented here extend our previous physiological characterization (Dougalis et al. 2012) and argue that DA neurons of the vlPAG/DRN express autorhythmicity in the absence of synaptic transmission via the interplay of potassium and sodium currents without the absolute need of calcium currents. The properties of the ionic currents recorded here (IH current, IA current), the lack of small oscillating potentials in the presence of sodium channel blockers taken together with the mechanisms for autorhythmicity (reliance more on sodium rather than calcium currents) also support further the idea that vlPAG/DRN DA neurons are operationally similar to VTA, rather than SNc, DA neurons. In particular, the properties of a slowly inactivating IA current in conjunction with the small and slowly activating IH current described herein pinpoint that vlPAG/DRN DA neurons are most similar to prefrontal cortex or medial shell of nucleus accumbens projecting DA neurons (see Lammel et al. 2008, 2011).
7.  Dynamics of ramping bursts in a respiratory pre-Botzinger Complex model (Abdulla et al, accepted)
This single-neuron model is, to the authors' knowledge, the first to capture the pre-inspiratory ramping aspects of preBotzinger Complex inspiratory neurons' activity patterns, in which relatively slow tonic spiking gradually progresses to faster spiking and a full-blown burst, with a corresponding gradual development of an underlying plateau potential. The key to this pattern is the incorporation of the dynamics of the extracellular potassium ion concentration, which is here integrated into an existing model for pre-BotC neuron bursting along with some parameter adjustments. Using fast-slow decomposition, this activity can be shown to be a form of parabolic bursting, but with burst termination at a homoclinic bifurcation rather than at a SNIC bifurcation.
8.  Function and energy constrain neuronal biophysics in coincidence detection (Remme et al 2018)
" ... We use models of conductance-based neurons constrained by experimentally observed characteristics with parameters varied within a physiologically realistic range. Our study shows that neuronal design of MSO cells does not compromise on function, but favors energetically less costly cell properties where possible without interfering with function."
9.  Human sleep-wake regulatory network model (Gleit et al 2013, Booth et al 2017)
A physiologically-based mathematical model of a sleep-wake regulatory network model for human sleep. The model simulates neurotransmitter-mediated interactions among hypothalamic and brainstem neuronal populations that promote wake, rapid eye movement (REM) sleep and non-REM (NREM) sleep. A neuronal population firing rate model formalism is used. The circadian rhythm pacemaker neuronal population, the suprachiasmatic nucleus (SCN), modulates activity in the wake- and sleep-promoting populations to entrain sleep-wake behavior to the ~24h circadian rhythm. A circadian clock oscillator model drives a 24h variation in the SCN firing rate and can be entrained to an externally imposed light:dark cycle. The default parameters replicate typical human sleep entrained to an external 14h:10h light:dark cycle
10.  Model of AngII signaling and membrane electrophysiology (Makadia, Anderson, Fey et al., 2015)
We developed a novel multiscale model to bridge neuropeptide receptor-activated signaling pathway with membrane electrophysiology. The model studies the effects of Angiotensin II (AngII) on neuronal excitability changes mediated by signaling dynamics and downstream phosphorylation of ion channels. The multiscale model was implemented as a set of ordinary differential equations solved using the ode15s solver in Matlab (Mathworks, USA). The signaling reactions were modeled with either mass-action or Michaelis--Menten kinetics and ion channel electrophysiology was modeled according to the Hodgkin-Huxley formalism. These models were initially validated against their respective data domains independently and were integrated to develop a multiscale model of signaling and electrophysiology.
11.  Modelling platform of the cochlear nucleus and other auditory circuits (Manis & Compagnola 2018)
"Models of the auditory brainstem have been an invaluable tool for testing hypotheses about auditory information processing and for highlighting the most important gaps in the experimental literature. Due to the complexity of the auditory brainstem, and indeed most brain circuits, the dynamic behavior of the system may be difficult to predict without a detailed, biologically realistic computational model. Despite the sensitivity of models to their exact construction and parameters, most prior models of the cochlear nucleus have incorporated only a small subset of the known biological properties. This confounds the interpretation of modelling results and also limits the potential future uses of these models, which require a large effort to develop. To address these issues, we have developed a general purpose, bio-physically detailed model of the cochlear nucleus for use both in testing hypotheses about cochlear nucleus function and also as an input to models of downstream auditory nuclei. The model implements conductance-based Hodgkin-Huxley representations of cells using a Python-based interface to the NEURON simulator. ..."
12.  Neural mass model of the neocortex under sleep regulation (Costa et al 2016)
This model generates typical human EEG patterns of sleep stages N2/N3 as well as wakefulness and REM. It further contains a sleep regulatory component, that lets the model transition between those stages independently
13.  Respiratory central pattern generator (mammalian brainstem) (Rubin & Smith 2019)
This model includes a conditional respiratory pacemaker unit (representing the pre-Botzinger Complex), which can be tuned across oscillatory and non-oscillatory dynamic regimes in isolation, embedded into a full respiratory network. The work shows that under this embedding, the pacemaker unit's dynamics become masked: the network exhibits similar dynamical properties regardless of the conditional pacemaker node's tuning, and that node's outputs are dominated by network influences.
14.  Respiratory central pattern generator including Kolliker-Fuse nucleus (Wittman et al 2019)
We present three highly reduced conductance-based models for the core of the respiratory CPG. All successfully simulate respiratory outputs across eupnoeic and vagotomized conditions and show that loss of inhibition to the pontine Kolliker-Fuse nucleus reproduces the key respiratory alterations associated with Rett syndrome.
15.  Respiratory control model with brainstem CPG and sensory feedback (Diekman, Thomas, and Wilson 2017)
This is a closed-loop respiratory control model incorporating a central pattern generator (CPG), the Butera-Rinzel-Smith (BRS) model, together with lung mechanics, oxygen handling, and chemosensory components. The closed-loop system exhibits bistability of bursting and tonic spiking. Bursting corresponds to coexistence of eupnea-like breathing, with normal minute ventilation and blood oxygen level. Tonic spiking corresponds to a tachypnea-like state, with pathologically reduced minute ventilation and critically low blood oxygen. In our paper, we use the closed-loop system to demonstrate robustness to changes in metabolic demand, spontaneous autoresuscitation in response to hypoxia, and the distinct mechanisms that underlie rhythmogenesis in the intact control circuit vs. the isolated, open-loop CPG.
16.  Zebrafish Mauthner-cell model (Watanabe et al 2017)
The NEURON model files encode the channel generator and firing simulator for simulating development and differentiation of the Mauthner cell (M-cell) excitability in zebrafish. The channel generator enables us to generate arbitrary Na+ and K+ channels by changing parameters of a Hodgkin-Huxley model under emulation of two-electrode voltage-clamp recordings in Xenopus oocyte system. The firing simulator simulates current-clamp recordings to generate firing patterns of the model M-cell, which are implemented with arbitrary-generated basic Na+ and K+ conductances and low-threshold K+ channels Kv7.4/KCNQ4 and sole Kv1.1 or Kv1.1 coexpressed with Kvbeta2.

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