Invited MinireviewInfection-induced viscerosensory signals from the gut enhance anxiety: Implications for psychoneuroimmunology
Section snippets
1. Introduction
In the late 1800s William James, a psychologist at Harvard University, published a provocative theory of emotion: that the perception of emotions follows from perception of our physical responses to cognitive apprehension of external threats (or more pleasant stimuli). That is: the experience of emotion is integrated with somato- and viscerosensory signals that result from cognitively driven motor, neuroendocrine, or autonomic responses, in a kind of brain–body–brain “loop” communication
2. Infection-induced anxiety
We first became involved with these issues when one of us (ML) observed that mice treated per-orally with live bacteria (Campylobacter jejuni) seemed more anxious than saline-treated control mice (Lyte et al., 1998). This observation was confirmed by comparing the behavior of C. jejuni-treated mice and control mice on the elevated plus maze. However, there was no evidence that the bacteria had reached the systemic circulation (and thus the brain), or that the infection induced circulating
3. Brain substrates for infection-induced anxiety-like behavior
As James predicted and as recent studies now support, brain regions involved in emotions are associated with viscerosensory and autonomic (visceral motor) processing (Craig, 2003, Nauta, 1971, Price, 1999, Zagon, 2001). Previous studies using immune challenges with bacterial products (LPS) or cytokines, such as IL-1, that usually induce symptoms of behavioral depression have indicated that, indeed, these immune stimuli also activate brain regions involved in viscerosensory processing (Goehler
4. What may be the adaptive value of enhanced anxiety during gut infection?
An important issue to keep in mind regarding experiments investigating emotional states in animals, especially anxiety, is that the characteristics of the testing procedure influence the findings. In the case of the open field/hole board, this apparatus represents a possibly dangerous novel environment. It can be thought of as analogous to that which an animal might encounter when foraging in an unknown area for food, or in any other exploratory behavior in the wild. The open character of the
5. Bidirectional interactions of bacteria/immune-brain-gut axis: “Bottom–up” and “top–down” influences on gastrointestinal health and mood
One of the core principles of psychoneuroimmunology is the bidirectional influence of the immune and nervous systems on mood and health. That is, affective symptoms associated with illness or inflammation follow not only from stress of dealing with a medical condition, or personality factors (“top–down” brain-mediated) but also from the effects of cytokines, or other products of inflammation, induced by infection or inflammation (“bottom–up” immune and viscerosensory mediated). In the case of
6. Conclusion
It seems reasonable to assert that linking emotions to homeostatic mechanisms conveys powerful adaptive advantages, as this is a salient way for conditions within the body to influence behavior. In the case of infection-induced anxiety, increasing cautiousness in an animal that may soon become ill could save its life. In a similar way, the development of a conditioned taste aversion (a learned negative association of recently eaten food with illness) following the survival of food poisoning
Acknowledgments
This work was supported by NIH Grants MH50431, MH64648, and MH68834.
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