The Electroneuropathology of Prion Disease

Neuropathological studies can reveal a great deal about the appearance of cells and structures within the nervous system during the course of a disease, but they cannot determine which neurons were working properly when the samples were taken or in the period before death. Neurons may look normal, but are they still able to integrate incoming synaptic information, to generate and propagate action potentials, and lay the foundations of new memories? The answers to these questions are central to the understanding of the relationships between neuropathological abnormalities and particular signs or symptoms. Prion diseases also affect laboratory animals, and, as a consequence, it is possible to study them in great detail, from the presymptomatic to the terminal stages. Of course, mice do not report symptoms, but it is possible to assess their health status by using scoring systems such as those described by Irwin ( 1 ), and behavioral tests can, to some extent, model psychiatric disturbances. The crucial benefit is that the functioning of neurons can be assessed in a pathological and behavioral context. The possibility thereby exists to relate abnormalities in the electrophysiological properties of neurons, or groups of neurons, to particular neuropathological or behavioral changes. We have called this approach “electroneuropathology” (Fig.1 ) ( 2 ).

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