Microbiota from young mice counteracts selective age-associated behavioral deficits.

The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmunity during aging processes. Therefore, we conducted fecal microbiota transplantation from either young (3-4 months) or old (19-20 months) donor mice into aged recipient mice (19-20 months). Transplant of a microbiota from young donors reversed aging-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. Our results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging.

The Microbiota-Gut-Brain Axis.

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.

Facilitation and retardation of flavor preference conditioning following prior exposure to the flavor conditioned stimulus.

In two experiments, rats received pairings of an almond flavor (Experiments 1 and 2B) or a vanilla flavor (Experiment 2A) with sucrose. In each experiment, half of the rats received prior exposure to the flavor and half were exposed to water. Conditioned preference was then assessed through two-bottle, flavor versus water, choice tests. Latent inhibition (indicated by a weaker preference in pre-exposed subjects) was observed in the experiment using the vanilla flavor. However, facilitation (a stronger preference in pre-exposed subjects) instead of latent inhibition was evident with the almond flavor, both across acquisition trials and in the final choice test. These results indicate that, unlike most other paradigms of Pavlovian conditioning, conditioned stimulus pre-exposure in flavor preference learning may either facilitate or retard the acquisition (or the expression) of a conditioned flavor preference. We explore the proposal that the critical difference between the flavors lies in their hedonic values, with facilitation being more likely in a flavor that is initially disliked.

The extinction procedure modifies a conditioned flavor preference in nonhungry rats only after revaluation of the unconditioned stimulus.

In 3 experiments rats experienced 2 flavors, each paired with sucrose, in order to establish a conditioned preference to each. One (flavor Fe) was then presented alone (an extinction procedure) prior to a choice test between Fe and the flavor that did not undergo extinction (Fne). Hungry rats showed a preference for Fne over Fe (Experiment 1A), but rats that were not food-deprived showed no effect of extinction when given a choice between Fe and Fne immediately after extinction (Experiment 1B) or after an interval in which reexposure to sucrose was given (Experiment 2). The extinction procedure was not without effect, however, as Fe was preferred over Fne after sucrose had been devalued by pairing with lithium chloride, and Fne was preferred over Fe after a procedure likely to enhance the value of the sucrose (Experiment 3). The explanations considered propose that preference conditioning establishes a range of associations between the flavor and the various properties of sucrose (its nutritional value, its taste, the hedonic reaction it evokes). It is suggested that the form of learning that mediates revaluation effects is sensitive to extinction whereas that responsible for performance on a consumption test is not. (PsycINFO Database Record

Latent inhibition in flavor-preference conditioning: effects of motivational state and the nature of the reinforcer.

In two experiments, rats received pairings of the flavor of almond with either fructose or maltodextrin, and the conditioned preference for almond was then tested. In each experiment, half of the rats had received prior exposure to almond on its own, and half had received no preexposure. In Experiment 1, in which the rats were hungry during the test, the preference was greater in the nonpreexposed subjects, both for those trained with fructose and those trained with maltodextrin; that is, latent inhibition was obtained with both reinforcers. In Experiment 2, in which the rats were not food deprived prior to the test, not only was there no latent inhibition with either of the reinforcers, but, for both, the preference was greater for preexposed than for nonpreexposed subjects. These results give no support to the proposal that different types of reinforcer generate different types of learning. They are, however, consistent with the proposal that different types of learning control behavior when a rat is hungry and when it is not, and that the form that generates the preference in the latter case is not susceptible to the latent inhibition effect.