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Manuscript Submission Deadline 30 June 2023

Neurons and neuronal circuits must deliver their functions despite ongoing changes in the environmental conditions, and in many cases, they must do so throughout the life of the organism. The different mechanisms that underlie neuronal resilience operate over a wide range of time scales. Neurons are able to ...

Neurons and neuronal circuits must deliver their functions despite ongoing changes in the environmental conditions, and in many cases, they must do so throughout the life of the organism. The different mechanisms that underlie neuronal resilience operate over a wide range of time scales. Neurons are able to instantaneously cope with some perturbations such as acute changes in temperature. Over longer time scales they can recover from failure and can adapt in order to function in the presence of genetic and pharmacological manipulations. They must also endure life-long challenges such as protein turnover, and in some cases, changes in their size.

The instantaneous or short-term response of neurons and circuits to perturbations is thought to be determined by their excitability properties. Neurons express multiple different types of ion channels which are thought to exhibit overlapping properties. Because of this, failure or malfunction of an ionic current type could in principle be compensated by another current type. In computational models this overlap has been associated with the concept of ion channel degeneracy: multiple different combinations of ion channel densities result in similar patterns of activity or functions. Thus, it’s been suggested that ion channel degeneracy is important for resilience, as it provides neurons and circuits with different “strategies” to cope with perturbations. When perturbations are sufficiently extreme, neurons and circuits eventually display anomalous activity and cease to function. Interestingly, experiments show that circuits that have similar control activity become dysfunctional or “crash” in completely different ways, perhaps because they are using different combinations of ionic currents.

There are perturbations that cause neurons and circuits to become dysfunctional initially, but for which function can be recovered over longer time scales. Experiments identified and characterized some of the molecular processes that underlie such recovery processes, like stress-induced chaperone proteins that modulate the activities of the ionic channels. Neuromodulators are capable of drastically changing the excitability of neurons and are also thought to play a role in function recovery. Theoretical work in pacemaker circuits suggests that neurons and circuits can self-assemble into their functional configurations, and therefore withstand and recover from perturbations, via activity-dependent homeostasis. In this view, neurons can sense their activities and use this information to regulate their channel densities so that a specific target output pattern or function is attained. Homeostatic mechanisms are also at play in large circuits such as cortical networks. It is widely accepted that normal brain function requires the regulation of firing rates. Firing rate homeostasis (FRH) has been reported in experiments both in vertebrate and invertebrate neurons, as well as in cortical neurons. Computational models suggest that negative feedback processes are one of the main mechanisms underlying FRH in large neuronal networks.

The aim of this topic is to bring together opinion, review, and original research articles addressing questions about neuronal resilience and homeostasis across multiple time scales, both in small and large circuits, including (but not limited to):

- Molecular mechanisms of recovery processes: stress-induced proteins, role of neuromodulation
- Experiments showing neurons and circuits losing and recovering activity.
- Mechanistic models of homeostasis at the single cell and network levels, and firing rate homeostasis.
- Mechanistic models of instantaneous resilience at the single cell and network levels
- Relationship between ion channel degeneracy and instantaneous resilience.
- Role of neuromodulators in recovery processes.

Keywords: Neuronal Resilience, Ionic Channel Degeneracy, Loss and Recovery of Funcion, Activity-dependent Homeostasis, Firing Rate Homeostasis


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