Emergent effects of synaptic connectivity on the dynamics of global and local slow waves in a large-scale thalamocortical network model of the human brain.

Slow-wave sleep (SWS), characterized by slow oscillations (SO, <1Hz) of alternating active and silent states in the thalamocortical network, is a primary brain state during Non-Rapid Eye Movement (NREM) sleep. In the last two decades, the traditional view of SWS as a global and uniform whole-brain state has been challenged by a growing body of evidence indicating that SO can be local and can coexist with wake-like activity. However, the understanding of how global and local SO emerges from micro-scale neuron dynamics and network connectivity remains unclear. We developed a multi-scale, biophysically realistic human whole-brain thalamocortical network model capable of transitioning between the awake state and slow-wave sleep, and we investigated the role of connectivity in the spatio-temporal dynamics of sleep SO. We found that the overall strength and a relative balance between long and short-range synaptic connections determined the network state. Importantly, for a range of synaptic strengths, the model demonstrated complex mixed SO states, where periods of synchronized global slow-wave activity were intermittent with the periods of asynchronous local slow-waves. Increase of the overall synaptic strength led to synchronized global SO, while decrease of synaptic connectivity produced only local slow-waves that would not propagate beyond local area. These results were compared to human data to validate probable models of biophysically realistic SO. The model producing mixed states provided the best match to the spatial coherence profile and the functional connectivity estimated from human subjects. These findings shed light on how the spatio-temporal properties of SO emerge from local and global cortical connectivity and provide a framework for further exploring the mechanisms and functions of SWS in health and disease.

A modeling framework for adaptive collective defense: crisis response in social-insect colonies.

Living systems, from cells to superorganismic insect colonies, have an organizational boundary between inside and outside and allocate resources to defend it. Whereas the micro-scale dynamics of cell walls can be difficult to study, the adaptive allocation of workers to defense in social-insect colonies is more conspicuous. This is particularly the case for Tetragonisca angustula stingless bees, which combine different defensive mechanisms found across other colonial animals: (1) morphological specialization (distinct soldiers (majors) are produced over weeks); (2) age-based polyethism (young majors transition to guarding tasks over days); and (3) task switching (small workers (minors) replace soldiers within minutes under crisis). To better understand how these timescales of reproduction, development, and behavior integrate to balance defensive demands with other colony needs, we developed a demographic Filippov ODE system to study the effect of these processes on task allocation and colony size. Our results show that colony size peaks at low proportions of majors, but colonies die if minors are too plastic or defensive demands are too high or if there is a high proportion of quickly developing majors. For fast maturation, increasing major production may decrease defenses. This model elucidates the demographic factors constraining collective defense regulation in social insects while also suggesting new explanations for variation in defensive allocation at smaller scales where the mechanisms underlying defensive processes are not easily observable. Moreover, our work helps to establish social insects as model organisms for understanding other systems where the transaction costs for component turnover are nontrivial, as in manufacturing systems and just-in-time supply chains.

Alternative model systems for cognitive variation: eusocial-insect colonies.

Understanding the origins and maintenance of cognitive variation in animal populations is central to the study of the evolution of cognition. However, the brain is itself a complex, hierarchical network of heterogeneous components, from diverse cell types to diverse neuropils, each of which may be of limited use to study in isolation or prohibitively challenging to manipulate in situ. Consequently, highly tractable alternative model systems may be valuable tools. Eusocial-insect colonies display emergent cognitive-like properties from relatively simple social interactions between diverse subunits that can be observed and manipulated while operating collectively. Here, we review the individual-scale mechanisms that cause group-level variation in how colonies solve problems analogous to cognitive challenges faced by brains, like decision-making, attention, and search.

Dynamics of prion proliferation under combined treatment of pharmacological chaperones and interferons.

Prions are proteins that cause fatal neurodegenerative diseases. The misfolded conformation adopted by prions can be transmitted to other normally folded proteins. Therapeutics to stop prion proliferation have been studied experimentally; however, it is not clear how the combination of different types of treatments can decrease the growth rate of prions in the brain. In this article, we combine the implementation of pharmacological chaperones and interferons to develop a novel model using a non-linear system of ordinary differential equations and study the quantitative effects of these two treatments on the growth rate of prions. This study aims to identify how the two treatments affect prion proliferation, both individually and in tandem. We analyze the model, and qualitative global results on the disease-free and disease equilibria are proved analytically. Numerical simulations, using parameter values from in vivo experiments that provide a pharmaceutically important demonstration of the effects of these two treatments, are presented here. This mathematical model can be used to identify and optimize the best combination of the treatments within their safe ranges.