Degeneracy in the nervous system: from neuronal excitability to neural coding

Abstract

Degeneracy is ubiquitous across biological systems where structurally different elements can yield a similar outcome. Degeneracy is of particular interest in neuroscience too. On the one hand, degeneracy confers robustness to the nervous system and facilitates evolvability: Different elements provide a backup plan for the system in response to any perturbation or disturbance. On the other, a difficulty in the treatment of some neurological disorders such as chronic pain is explained in light of different elements all of which contribute to the pathological behavior of the system. Under these circumstances, targeting a specific element is ineffective because other elements can compensate for this modulation. Understanding degeneracy in the physiological context explains its beneficial role in the robustness of neural circuits. Likewise, understanding degeneracy in the pathological context opens new avenues of discovery to find more effective therapies.

Degeneracy in epilepsy: Multiple Routes to Hyperexcitable Brain Circuits and their Repair

“…In fact, to repair a failed degenerate system, it is often not enough to restore a single target mechanism (Figure 4). One reason for this is that, due to degeneracy, many different pathologically altered mechanisms are sufficient, but usually none of them is by itself necessary for pathological malfunction (Kamaleddin, 2022). In addition, a degenerate nervous system sometimes displays compensatory adaptations, which undermine therapeutic interventions focusing on a single target (Ratté et al, 2014;Ratté and Prescott, 2016).…”

“…Degeneracy, "the ability of elements that are structurally different to perform the same function or yield the same output" (Edelman and Gally, 2001), is a general principle, present in most complex adaptive biological systems (Tononi et al, 1999;Edelman and Gally, 2001). Degeneracy should be distinguished from redundancy, which results from multiple identical elements performing the same function (Edelman and Gally, 2001;Mason et al, 2015;Man et al, 2016;Kamaleddin, 2022; but see also Mizusaki and O'Donnell, 2021). In contrast to redundant components, degenerate components may generate dissimilar outputs in different contexts (Tononi et al, 1999;Morozova et al, 2022).…”

“…It is becoming increasingly clear that also the brain exhibits degeneracy (Edelman and Gally, 2001;Mason et al, 2015;Cropper et al, 2016;Ratté and Prescott, 2016;Seifert et al, 2016;Marder et al, 2017), with similar physiologi-cal states arising from a multitude of different subcellular, cellular and synaptic mechanisms (Prinz et al, 2004;Marder and Taylor, 2011; for recent reviews see Rathour and Narayanan, 2019;Goaillard and Marder, 2021;Kamaleddin, 2022). However, not only similar physiological but also similar pathological brain states may arise from structurally disparate mechanisms (Neymotin et al, 2016;Ratté and Prescott, 2016;O'Leary, 2018;Kamaleddin, 2022). Therefore, the existence of degeneracy in the brain has important implications for understanding and treating complex brain disorders such as epilepsy.…”

Pareto optimality, economy–effectiveness trade-offs and ion channel degeneracy: improving population modelling for single neurons

“…Degeneracy [7] is present at all scales of the brain (figure 1). Its importance for the flexibility and robustness of brain functions has been increasingly acknowledged in recent years (for reviews see [9][10][11]). Accordingly, ion channel degeneracy has been linked to the flexibility [4] and robustness of neuronal behaviour [10,12,13].…”

Modelling the contributions to hyperexcitability in a mouse model of Alzheimer’s disease

“…Second, in line with a multi-causal pathogenesis, we showed that the increased excitability of CA1 pyramidal cells can be sufficiently accounted for by a shift in E/I balance towards glutamatergic network excitation (increased network burst activity and decreased inhibitory inputs) or by its combination with changes in ion channel expression ( I AHP channel density down-regulated; I Nap , I Na and I CaT up-regulated). Our results are in line with the concept of degeneracy (Tononi et al ., 1999; Edelman and Gally, 2001), according to which similar physiological but also similar pathological states such as neural hyperexcitability can emerge from multiple structurally distinct mechanisms (Neymotin et al ., 2016; Ratté and Prescott, 2016; O’Leary, 2018; Kamaleddin, 2022; Medlock et al ., 2022; Stö ber et al ., 2022).…”