The Wistar Audiogenic Rat (WAR) strain and its contributions to epileptology and related comorbidities: History and perspectives.

In the context of modeling epilepsy and neuropsychiatric comorbidities, we review the Wistar Audiogenic Rat (WAR), first introduced to the neuroscience international community more than 25years ago. The WAR strain is a genetically selected reflex model susceptible to audiogenic seizures (AS), acutely mimicking brainstem-dependent tonic-clonic seizures and chronically (by audiogenic kindling), temporal lobe epilepsy (TLE). Seminal neuroethological, electrophysiological, cellular, and molecular protocols support the WAR strain as a suitable and reliable animal model to study the complexity and emergent functions typical of epileptogenic networks. Furthermore, since epilepsy comorbidities have emerged as a hot topic in epilepsy research, we discuss the use of WARs in fields such as neuropsychiatry, memory and learning, neuroplasticity, neuroendocrinology, and cardio-respiratory autonomic regulation. Last, but not least, we propose that this strain be used in "omics" studies, as well as with the most advanced molecular and computational modeling techniques. Collectively, pioneering and recent findings reinforce the complexity associated with WAR alterations, consequent to the combination of their genetically-dependent background and seizure profile. To add to previous studies, we are currently developing more powerful behavioral, EEG, and molecular methods, combined with computational neuroscience/network modeling tools, to further increase the WAR strain's contributions to contemporary neuroscience in addition to increasing knowledge in a wide array of neuropsychiatric and other comorbidities, given shared neural networks. During the many years that the WAR strain has been studied, a constantly expanding network of multidisciplinary collaborators has generated a growing research and knowledge network. Our current and major wish is to make the WARs available internationally to share our knowledge and to facilitate the planning and execution of multi-institutional projects, eagerly needed to contribute to paradigm shifts in epileptology. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".