Abstract

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.

Highlights

  • When the needs of an animal require the execution of particular behaviours, the brain must decide which of these needs to prioritise–whether to flee from or fight an aggressor

  • The ventromedial nucleus of the hypothalamus (VMN) is a large hypothalamic nucleus with an important role in diverse behaviours stretching beyond its classic role in appetite regulation and energy homeostasis [1]

  • How might this behaviour arise in the neuronal networks within the VMN? The neurons of this nucleus are densely interconnected, and the great majority of them are glutamatergic: mRNA for the vesicle glutamate transporter VGLUT2 is densely expressed throughout the VMN, while the VMN is virtually devoid of GAD65 and GAD67 mRNA, indicating that it contains few intrinsic GABA neurons [19]

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Summary

Introduction

The ventromedial nucleus of the hypothalamus (VMN) is a large hypothalamic nucleus with an important role in diverse behaviours stretching beyond its classic role in appetite regulation and energy homeostasis [1]. It has been suggested that a ‘switch’ in the VMN might underlie the reciprocal gating of sexual and feeding behaviour [18] This suggests that the VMN is a multi-stable network–that, at any given time, its output is in one of a discrete number of possible states corresponding to discrete motivational drives. How might this behaviour arise in the neuronal networks within the VMN? The neurons of this nucleus are densely interconnected, and the great majority of them are glutamatergic: mRNA for the vesicle glutamate transporter VGLUT2 is densely expressed throughout the VMN, while the VMN is virtually devoid of GAD65 and GAD67 mRNA, indicating that it contains few intrinsic GABA neurons [19] This suggests that VMN neurons are extensively interconnected by mutually excitatory pathways

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