My research uses sleep as a model behavior for the study of neural-immune interactions, focusing on two questions: How does the immune system communicate with the brain to modify behavior?  What mechanisms mediate illness-associated behaviors like excessive sleepiness and fatigue?  To date, my work has used animal models to demonstrate that alterations in sleep accompany infectious diseases of diverse etiologies.  These sleep changes vary with the infectious organism, its viability, and the route of inoculation and are influenced by the immune competence, exposure history, environment, and genetic background of the animal.

   My long-term goal is to define the causes of fatigue and altered sleepiness during infectious disease.  To that end, I recently completed an analysis of genetic contributions to altered sleep patterns in influenza-infected mice.  This analysis revealed that quantitative trait locus, Srilp1, that accounts for large and consistent differences in influenza-related alterations in sleep in different strains of inbred mice.  Future work will build on that finding by using genetic mapping and a candidate gene strategy to identify the genetic and pathologic mechanisms that mediate sleep responses to influenza infection and other types of microbial challenges.  Identifying the genes that influence sleep during infections is an important step toward discovering substances that influence disease susceptibility and symptoms.  Studying the mechanisms by which genes and their products modulate sleep will ultimately improve our understanding of the processes that control normal sleep and that contribute to sleep disorders.

SELECTED REFERENCES:

Toth LA, SJ Verhulst. Strain differences in sleep patterns of healthy and influenza-infected inbred mice. Behav Genet 33:323-334, 2003

Toth LA, LF Hughes. Macrophage participation in influenza-induced sleep enhancement in C57BL/6J mice. Brain Behav Immun 18:375-389, 2004

Toth LA, LF Hughes, JE Rehg. Sleep and activity during concanavalin-A-induced hepatitis and peritonitis in inbred mice. Sleep 28:571-585, 2005.

Ding M, LA Toth. mRNA expression in mouse hypothalamus and basal forebrain during influenza infection: a novel model for sleep regulation. Physiological Genomics 24:225-234, 2006

Toth LA, LR Hughes. Sleep and temperature responses of inbred mice with Candida albicans-induced pyelonephritis Comp Med (in press)

Jhaveri K, LA Toth, V Ramkumar. Nitric oxide serves as an endogenous regulator of neuronal adenosine A1 receptor expression. J Neurochem (in press)

Jhaveri K, V Ramkumar, RA Trammell, LA Toth. Spontaneous, homeostatic, and inflammation-induced sleep in NF-?B p50 knockout mice. Am J Physiol (In press)