Degeneracy

(This article is inspired by my thread on X: https://x.com/prmshra/status/1784816045867385262 )

Neuroscience has long been fascinated by the brain's complexity. one of its most intriguing aspects, degeneracy, remains a relatively obscure concept. Recently, Dr. Christophe Bernard explored degeneracy as a fundamental principle in neuroscience.Let's explain this conundrum.

What is degeneracy?

different structures

or processes

leading to same outcome or function.

Unlike redundancy (identicals performing same function) degeneracy involves diverse elements that can produce similar OR different outcomes based on the context. This versatility is crucial for natural selection.

This is found at all levels of biological organization, from the genes to evolution. by providing multiple ways to achieve the same function, redundancy enhances robustness and adaptability, ensuring that organisms can thrive in diverse environments.

For example: gene knockouts in mice often show no phenotypic effects, demonstrating that other genes can compensate for the loss.

From: Wang et al. "The recent advances and future perspectives of genetic compensation studies in the zebrafish model", Genes & Diseases

Another example: degeneracy is exemplified by the genetic code, where multiple codons can encode for the same amino acid. This redundancy allows for flexibility in protein synthesis and ensures that mutations in DNA may not always lead to changes in protein function.

In cellular systems, degeneracy is observed in gene regulation. Different DNA can regulate vs code for protein, leading to the same gene expression.

different TFs can regulate gene expression in a degenerate manner.

This gets more interesting at the nerve level though. Neurons can connect in myriad ways to form functional circuits. synaptic plasticity = change in connectivity. different mechanisms give similar change in synaptic strength. This is crucial for learning and memory.

...more broadly, though, this means that the brain can achieve a specific function through various means, providing flexibility and resilience in the face of challenges. This, as Bernard points out, is often overlooked. Let's dive into the neuroscience.

At this level, degeneracy functionally refers to the ability of different neural structures or pathways to produce the same functional output. Consider how people with significant brain injuries often regain functions that were lost! i.e. diff. pathways compensate for damage

For example: the nervous system is not pre-wired with exact connections. Rather, connections form based on a variety of (EPI)genetic and environmental factors. This results in unique neural architectures that are functionally equivalent.

Epigenetics influences brains by modifying gene expression without altering the DNA sequence, affecting neural pathways development. This modulation is crucial in the brain's response to environmental changes. This has been my field of research.

The flexibility of the epigenome allows for the dynamic regulation of genes necessary for brain development and function, highlighting the role of degeneracy. Different epigenetic modifications can lead to similar neural outcomes. ergo, degeneracy underpins adaptability.

There are various specific studies done! One kind I love: hippocampus pyramidal neurons, highly crucial cells. In these neurons, certain features like spike-triggered averages (how neurons respond to inputs) can be achieved by many different combinations of molecular components, like ion channels. This variability shows that there isn't just one fixed way for neurons to operate. https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP283539…

Through experiments where scientists virtually "knock out" specific ion channels, they've found that flexibility in channels like HCN and transient potassium channels play key roles in managing how neurons respond to signals. This is crucial for things like learning and memory. https://ncbi.nlm.nih.gov/pmc/articles/PMC6962224/…

This flexibility allows our neurons to maintain stability while being adaptable to changes, which is essential for everything from simple daily tasks to complex thinking. Understanding this can lead to better treatments for neurological diseases.

This is part of why major variations in brain structures, such as the absence of the corpus callosum, allow everyday functions without noticeable deficits. You can call this as a result of a singular cause or not. at a systems biology level, it'd still be degeneracy!

Here is an example on the cognitive side: Efficient Information Coding (EIC). Imagine your brain's neurons as antennas, each fine-tuned to pick up certain signals. EIC is the brain's way of making sure that these 'antennas' aren’t wasting energy on background noise. It's like fine-tuning your car radio to get clear music without static.

what happens if one antenna goes wild=> This is where degeneracy in the brain is a game-changer.

It allows other antennas to adjust and pick up the slack, ensuring no signal is lost.

Degeneracy adds resilience to our neural networks, giving us a backup plan for information processing.

It means that our brain's coding efficiency doesn’t depend on just one pathway or set of neurons.

This combination keeps information processing in our brain robust, no matter what changes come our way. From: "Degeneracy: a link between evolvability, robustness and complexity in biological systems", Whitacre, 2010

Now, I could not cover every source of degeneracy even if I tried. I, as well as maybe no one, knows it all. :/ But by embracing the concept of degeneracy, we can use it in modelling. neuroscience can advance toward more accurate models of brain function that respect the diversity and complexity of neural processes. This shift could lead to more effective treatments and interventions. From: "Measures of degeneracy and redundancy in biological networks", Edelman et al. 1999

more generally, i hope this allows you to appreciate degeneracy, and its difference from redundancy. it is so incredibly important, and a pillar of systems biology.