1. Breakdown of Excitability by Attenuated PRV-152 Infection in Auditory Brainstem Neurons of Mongolian Gerbils
- Author
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Benedikt Grothe, Christian P. Porres, and Felix Felmy
- Subjects
0301 basic medicine ,Inferior colliculus ,Auditory Pathways ,Patch-Clamp Techniques ,Time Factors ,Secondary infection ,Green Fluorescent Proteins ,Central nervous system ,Action Potentials ,S100 Calcium Binding Protein beta Subunit ,In Vitro Techniques ,Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Patch clamp ,Neurons ,Pseudorabies ,General Neuroscience ,Lateral lemniscus ,Herpesvirus 1, Suid ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Neuroglia ,Brainstem ,Gerbillinae ,Microtubule-Associated Proteins ,Neuroscience ,Nucleus ,030217 neurology & neurosurgery ,Brain Stem - Abstract
Pseudorabies virus (PRV), a neurovirulent α-herpesvirus, spreads between neurons at synaptic connections. PRV-infected neurons have been shown to exhibit functional deficits with the attenuated PRV152 Bartha strain negatively influencing neuronal functioning in in vitro model systems. However, the impact of this attenuated PRV152 Bartha strain on the native central nervous system has not been fully explored. Using a combination of in vivo stereotactic injections and post-hoc in vitro whole-cell recordings, we investigated the functional impact of PRV152 Bartha in the auditory system of juvenile Mongolian gerbils. The specificity of this virus strain to spread exclusively trans-synaptically in a retrograde fashion and the well-defined structure of the ascending auditory brainstem pathways allowed us to determine the physiological alterations in primary and secondary infected neurons. We find at primary and secondary infections sites, the inferior colliculus (IC) and dorsal nucleus of the lateral lemniscus respectively, a reduced excitability of infected cells. The loss of excitability is manifested by an increase in current threshold and a loss of action potential generation. The minor changes in the approximated passive membrane parameters induced by the infection cannot explain the full loss in excitability, indicating that channel densities and properties have changed. This impact on neuronal functioning might contribute to the lethal neurovirulent effects of PRV viruses as vital neuronal circuits might cease activity. Since the detrimental effects of the attenuated PRV152 Bartha strain are reduced compared to wild-type strains, it comprises an excellent tool to study the neuropathological mechanisms of viral infections.
- Published
- 2017