Modeling Spiking and Secretion in the Magnocellular Vasopressin Neuron

MacGregor, Duncan J.; Leng, Gareth

doi:10.1002/9781119159438.ch5

Cited by 3 publications

(2 citation statements)

References 40 publications

(23 reference statements)

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“…The “slow DAP” cells have a peak in their hazard function that was previously attributed to a DAP. However, this could equally arise from a very fast HAP (mean λ HAP = 4.7 ms): if λ HAP is less than the PSP half-life (7.5 ms) then the accumulated EPSPs that have triggered the spike can have a depolarising effect that outlasts the HAP [26]. Only one of the “slow DAP” cells needed a DAP for the best fit.…”

Section: Resultsmentioning

confidence: 99%

Emergent decision-making behaviour and rhythm generation in a computational model of the ventromedial nucleus of the hypothalamus

MacGregor

Leng

2019

PLoS Comput Biol

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The ventromedial nucleus of the hypothalamus (VMN) has an important role in diverse behaviours. The common involvement in these of sex steroids, nutritionally-related signals, and emotional inputs from other brain areas, suggests that, at any given time, its output is in one of a discrete number of possible states corresponding to discrete motivational drives. Here we explored how networks of VMN neurons might generate such a decision-making architecture. We began with minimalist assumptions about the intrinsic properties of VMN neurons inferred from electrophysiological recordings of these neurons in rats in vivo , using an integrate-and-fire based model modified to simulate activity-dependent post-spike changes in neuronal excitability. We used a genetic algorithm based method to fit model parameters to the statistical features of spike patterning in each cell. The spike patterns in both recorded cells and model cells were assessed by analysis of interspike interval distributions and of the index of dispersion of firing rate over different binwidths. Simpler patterned cells could be closely matched by single neuron models incorporating a hyperpolarising afterpotential and either a slow afterhyperpolarisation or a depolarising afterpotential, but many others could not. We then constructed network models with the challenge of explaining the more complex patterns. We assumed that neurons of a given type (with heterogeneity introduced by independently random patterns of external input) were mutually interconnected at random by excitatory synaptic connections (with a variable delay and a random chance of failure). Simple network models of one or two cell types were able to explain the more complex patterns. We then explored the information processing features of such networks that might be relevant for a decision-making network. We concluded that rhythm generation (in the slow theta range) and bistability arise as emergent properties of networks of heterogeneous VMN neurons.

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Section: Resultsmentioning

confidence: 99%

Emergent decision-making behaviour and rhythm generation in a computational model of the ventromedial nucleus of the hypothalamus

MacGregor

Leng

2019

PLoS Comput Biol

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“…One interesting aspect of many neurophysiological systems is their ability to exhibit burst firing activity in their membrane voltage characterized by the emergence of repetitive clusters of action potentials (APs) separated by quiescent periods [20]. It has been suggested that such bursts are more efficient at releasing neurotransmitters and/or hormones as well as better at preventing receptors from desensitization compared to tonic firing [21]. Cerebellar Purkinje cells that receive synaptic inputs from CSCs, for example, are spontaneously active neurons that tonically fire, but their firing switches to bursting upon receiving inhibitory or excitability inputs, exhibiting different modes of burst firing [22].…”

Section: Introductionmentioning

confidence: 99%

Bursting in cerebellar stellate cells induced by pharmacological agents: Non-sequential spike adding

et al. 2020

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Cerebellar stellate cells (CSCs) are spontaneously active, tonically firing (5-30 Hz), inhibitory interneurons that synapse onto Purkinje cells. We previously analyzed the excitability properties of CSCs, focusing on four key features: type I excitability, non-monotonic first-spike latency, switching in responsiveness and runup (i.e., temporal increase in excitability during whole-cell configuration). In this study, we extend this analysis by using whole-cell configuration to show that these neurons can also burst when treated with certain pharmacological agents separately or jointly. Indeed, treatment with 4-Aminopyridine (4-AP), a partial blocker of delayed rectifier and A-type K+ channels, at low doses induces a bursting profile in CSCs significantly different than that produced at high doses or when it is applied at low doses but with cadmium (Cd2+), a blocker of high voltage-activated (HVA) Ca2+ channels. By expanding a previously revised Hodgkin–Huxley type model, through the inclusion of Ca2+-activated K+ (K(Ca)) and HVA currents, we explain how these bursts are generated and what their underlying dynamics are. Specifically, we demonstrate that the expanded model preserves the four excitability features of CSCs, as well as captures their bursting patterns induced by 4-AP and Cd2+. Model investigation reveals that 4-AP is potentiating HVA, inducing square-wave bursting at low doses and pseudo-plateau bursting at high doses, whereas Cd2+ is potentiating K(Ca), inducing pseudo-plateau bursting when applied in combination with low doses of 4-AP. Using bifurcation analysis, we show that spike adding in square-wave bursts is non-sequential when gradually changing HVA and K(Ca) maximum conductances, delayed Hopf is responsible for generating the plateau segment within the active phase of pseudo-plateau bursts, and bursting can become “chaotic” when HVA and K(Ca) maximum conductances are made low and high, respectively. These results highlight the secondary effects of the drugs applied and suggest that CSCs have all the ingredients needed for bursting.

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Phasic Neuronal Firing in the Rodent Nucleus of the Solitary Tract ex vivo

et al. 2021

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Phasic pattern of neuronal activity has been previously described in detail for magnocellular vasopressin neurons in the hypothalamic paraventricular and supraoptic nuclei. This characteristic bistable pattern consists of alternating periods of electrical silence and elevated neuronal firing, implicated in neuropeptide release. Here, with the use of multi-electrode array recordings ex vivo, we aimed to study the firing pattern of neurons in the nucleus of the solitary tract (NTS) – the brainstem hub for homeostatic, cardio-vascular, and metabolic processes. Our recordings from the mouse and rat hindbrain slices reveal the phasic activity pattern to be displayed by a subset of neurons in the dorsomedial NTS subjacent to the area postrema (AP), with the inter-spike interval distribution closely resembling that reported for phasic magnocellular vasopressin cells. Additionally, we provide interspecies comparison, showing higher phasic frequency and firing rate of phasic NTS cells in mice compared to rats. Further, we describe daily changes in their firing rate and pattern, peaking at the middle of the night. Last, we reveal these phasic cells to be sensitive to α2 adrenergic receptors activation and to respond to electrical stimulation of the AP. This study provides a comprehensive description of the phasic neuronal activity in the rodent NTS and identifies it as a potential downstream target of the AP noradrenergic system.

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Modeling Spiking and Secretion in the Magnocellular Vasopressin Neuron

Cited by 3 publications

References 40 publications

Emergent decision-making behaviour and rhythm generation in a computational model of the ventromedial nucleus of the hypothalamus

Emergent decision-making behaviour and rhythm generation in a computational model of the ventromedial nucleus of the hypothalamus

Bursting in cerebellar stellate cells induced by pharmacological agents: Non-sequential spike adding

Phasic Neuronal Firing in the Rodent Nucleus of the Solitary Tract ex vivo

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