How structure shapes (dys)function

Abstract

Structure is a key determinant of function, with the nervous system being no exception. For example, in the nervous system the physiological properties of different synapses may be understood by comparing their structures. However, it is not clear whether specific structural properties of some neurons might play a role in driving their selective removal during chronic neurodegeneration or whether the structural properties might underpin why particular types of synapses or other neuronal compartments are more susceptible to degeneration (i.e., become dysfunctional) in certain brain regions than in others. Our recent study of the ultrastructure of the hippocampus and the cerebellum revealed that early synaptic loss is not a ubiquitous event in a brain undergoing chronic neurodegeneration. The prominent structural differences in proximity of the synaptic environment that are brought about by a degree of synaptic ensheathment by glial cells may help explain why Purkinje cell synapses remain intact, while pyramidal cell synapses progressively degenerate. The intrinsic structural organization of the hippocampal neuropil could contribute to the susceptibility of synapses to extracellular protein misfolding by a relatively higher degree of synaptic exposure to the extracellular environment. We suggest that neuronal structure may determine more than function; it might also predict dysfunction.

Keywords: :

• structure-function relationship
• synaptic degeneration
• prion disease
• hippocampus
• cerebellum
• glial ensheathment

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Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

I am grateful to Jr-Prof Dr Stefan Remy, Dr Martin Fuhrmann, Dr Erdem Tamgüney (DZNE, Bonn, Germany) and Dr Marie-Ève Tremblay (Université Laval, Québec, Canada) for their comments and helpful discussions.