## 4 Discussion
The divergence in performance on the NOR task and _GABBR1_ expression (and many other genes) by the OF and OF + 2'-FL groups together with the relationship between the recognition index and _GABBR1_ expression highlight a potential mechanistic link connecting the two phenomena. To our knowledge, there has been little investigation into the connection between prebiotic intake and GABAergic processes. In context of probiotics, BALB/c mice orally gavageed with broth containing _L. rhamnus_ (JB-1) for 28 d displayed greater movement in an open field test, less time immobile during a forced swim test, greater entries to the open arm in an elevated plus maze, and increased memory on a fear conditioning task; indices demonstrating reduced response to stress and improved memory [54]. These changes were simultaneous with reduced mRNA expression of the \(GABA_{BIb}\) receptor in the amygdala, locus coeruleus, and hippocampus, and increased expression in the cingulate 1 and prelimbic cortices. A follow-up study using magnetic resonance spectroscopy in mice provided JB-1 demonstrated increased brain GABA after 4 weeks of consumption [55]. For object recognition, it appears that hippocampal reductions in GABA\({}_{\text{B}}\) receptor expression may be beneficial. [PERSON] et al. [52] proposed that downregulation of hippocampal GABA\({}_{\text{B}}\) receptor signaling may improve short term memory. In support of this hypothesis, Baclofen, a GABA\({}_{\text{B}}\) receptor agonist, has been shown to dose-dependently impair acquisition and storage of object recognition memory, whereas GABA\({}_{\text{B}}\) receptor antagonism can prevent baclofen-induced impairments [56]. Although the effects of GABA\({}_{\text{B}}\) agonist and antagonism vary by dose, route, and behavioral task used (for review see [PERSON] and [PERSON] [57]), it appears that both oligosaccharides and probiotics [54; 55] are linked to beneficial alteration of GABA receptor expression in the brain. While this study confirms several reports showing that various OS improve behavioral performance in both human and animal models [6; 13; 14; 21; 22; 23; 58], it is one of the first to examine the potential of human and non-human milk OS together. Adult mice and rats fed chow containing 0.312% or 0.625% 2\({}^{\prime}\)-FL for 12 or 5 weeks, respectively, showed increased and longer-lasting potentiation of Schaffer collateral neurons in the CA1 region of the hippocampus [13]. Supplemented mice displayed increased performance on place learning, working memory, and fixed-ratio lever-pressing tasks in an operant box, suggesting that 2\({}^{\prime}\)-FL supplementation enhanced multiple cognitive domains. In a follow-up study by the same group, subdiaphragmatic bilateral vagotomy was used to assess the requirement of the vagus nerve for 2\({}^{\prime}\)-FL-mediated increases in cognition in rodents [14]. Vagotomy abolished 2\({}^{\prime}\)-FL-mediated increases in hippocampal long-term potentiation. However, all groups (sham/vagotomy and control/2\({}^{\prime}\)-FL) were still able to perform above criterion in a fixed-ratio lever pressing task. By the end of training, 2\({}^{\prime}\)-FL/sham animals displayed greater lever presses than 2\({}^{\prime}\)-FL/vagotomy or control/vagotomy animals, indicating that while not required for behavioral performance, vagal communication is necessary for 2\({}^{\prime}\)-FL-induced increases. Together, these data suggest that the vagus nerve has a crucial role in mediating gut-brain-related increases in cognitive ability. Given the significant evidence described above demonstrating preliminary but growing data suggesting that prebiotics of many sources can improve cognition, there are few compelling arguments without speculation upon why. This extends to the present research, wherein alterations in brain volume and gene expression are not sufficient to describe the behavioral effects shown. Ultimately, the field of study is too young to make reasonable inferences on why prebiotics can improve cognition.