Degeneracy in hippocampal physiology and plasticity

ABSTRACT Degeneracy, defined as the ability of structurally disparate elements to perform analogous function, has largely been assessed from the perspective of maintaining robustness of physiology or plasticity. How does the framework of degeneracy assimilate into an encoding system where the ability to change is an essential ingredient for storing new incoming information? Could degeneracy maintain the balance between the apparently contradictory goals of the need to change for encoding and the need to resist change towards maintaining homeostasis? In this review, we explore these fundamental questions with the mammalian hippocampus as an example encoding system. We systematically catalog lines of evidence, spanning multiple scales of analysis, that demonstrate the expression of degeneracy in hippocampal physiology and plasticity. We assess the potential of degeneracy as a framework to achieve the conjoint goals of encoding and homeostasis without cross-interferences. We postulate that biological complexity, involving interactions among the numerous parameters spanning different scales of analysis, could establish disparate routes towards accomplishing these conjoint goals. These disparate routes then provide several degrees of freedom to the encoding-homeostasis system in accomplishing its tasks in an input- and state-dependent manner. Finally, the expression of degeneracy spanning multiple scales offers an ideal reconciliation to several outstanding controversies, through the recognition that the seemingly contradictory disparate observations are merely alternate routes that the system might recruit towards accomplishment of its goals. Against the backdrop of the ubiquitous prevalence of degeneracy and its strong links to evolution, it is perhaps apt to add a corollary to Theodosius Dobzhansky’s famous quote and state “nothing in physiology makes sense except in the light of degeneracy”. Highlights Degeneracy is the ability of structurally distinct elements to yield similar function We postulate a critical role for degeneracy in the emergence of stable encoding systems We catalog lines of evidence for the expression of degeneracy in the hippocampus We suggest avenues for research to explore degeneracy in stable encoding systems Dobzhansky wrote: “nothing in biology makes sense except in the light of evolution” A corollary: “nothing in physiology makes sense except in the light of degeneracy”