Neurological Sequelae Resulting from Encephalitic Alphavirus Infection

This review will cover zoonotic, encephalitic alphaviruses in the family Togaviridae. Encephalitic alphaviruses, i.e. Western- (WEEV), Eastern- (EEEV), Venezuelan equine encephalitis virus (VEEV) and, more rarely, Ross River virus, Chikungunya virus and Highlands J virus (HJV), are neuroinvasive and may cause neurological symptoms ranging from mild (e.g., febrile illness) to severe (e.g., encephalitis) in humans and equines. Among the naturally occurring alphaviruses, WEEV, EEEV and VEEV have widespread distributions in North, Central and South America. WEEV has found spanning the U.S. from the mid-West (Michigan and Illinois) to the West coast and extending to Canada with human cases reported in 21 states. EEEV is found along the Gulf (Texas to Florida) and Atlantic Coast (Georgia to New Hampshire), as well as in the mid-West (Wisconsin, Illinois and Michigan) and in Canada, with human cases reported in 19 states. In contrast, transmission of VEEV occurs predominantly in Central and South America. As with their geographical distribution, equine encephalitis viruses differ in their main mosquito vector species and their zoonotic potential. Copyright 2009 Elsevier B.V. All rights reserved.

The latency of the acoustic startle reflex in the rat is 8 msec, measured from tone onset to the beginning of the electromyographic response in the hindleg. This extremely short latency indicates that only a few synapses could be involved in some primary acoustic startle circuit. Acoustic startle is being used as a model system for studying habituation, sensitization, prepulse inhibition, classical conditioning, fear or anxiety, and drug effects on behavior. The present study attempted to delineate a short latency acoustic startle circuit, since this would provide critical information for further study in all of these areas. Bilateral lesions of the ventral cochlear nucleus, which receives the primary auditory input, abolish acoustic startle. Electrical, single pulse stimulation of the ventral cochlear nucleus elicits startle-like responses with a latency of about 7 msec. Bilateral lesions of the dorsal and ventral nuclei of the lateral lemniscus, which receive direct input from the ventral cochlear nuclei, abolish acoustic startle. Electrical stimulation of these nuclei elicits startle-like responses with a latency of about 6 msec. Bilateral lesions of ventral regions of the nucleus reticularis pontis caudalis, which contain cell bodies that give rise to the reticulospinal tract, abolish acoustic startle. Electrical stimulation of these points elicits startle-like responses with a latency of about 5 msec. Reaction product from horseradish peroxidase iontophoresed into this area is found in the nuclei of the lateral lemniscus. In contrast, lesions of the dorsal cochlear nuclei, vestibular nuclei, nucleus reticularis pontis oralis, nucleus reticularis gigantocellularis, and dorsal regions of the nucleus reticularis pontis caudalis fail to abolish acoustic startle. Also, "startle" cannot be elicited electrically from these areas. The data suggest that a primary acoustic startle circuit in the rat consists of auditory nerve, ventral cochlear nucleus, nuclei of the lateral lemniscus, nucleus reticularis pontis caudalis, spinal interneuron, lower motor neuron, and muscles. Hence, five synapses, plus the neuromuscular junction, are probably involved.