Cognition can reveal itself in the pupil, as latent cognitive processes map onto specific pupil responses. For instance, the pupil dilates when we make decisions and these pupil size fluctuations reflect decision-making computations during and after a choice. Surprisingly little is known, however, about how pupil responses relate to decisions driven by the learned value of stimuli. This understanding is important, as most real-life decisions are guided by the outcomes of earlier choices. The goal of this study was to investigate which cognitive processes the pupil reflects during value-based decision-making. We used a reinforcement learning task to study pupil responses during value-based decisions and subsequent decision evaluations, employing computational modeling to quantitatively describe the underlying cognitive processes. We found that the pupil closely tracks reinforcement learning processes independently across participants and across trials. Prior to choice, the pupil dilated as a function of trial-by-trial fluctuations in value beliefs about the to-be chosen option and predicted an individual’s tendency to exploit high value options. After feedback a biphasic pupil response was observed, the amplitude of which correlated with participants’ learning rates. Furthermore, across trials, early feedback-related dilation scaled with value uncertainty, whereas later constriction scaled with signed reward prediction errors. These findings show that pupil size fluctuations can provide detailed information about the computations underlying value-based decisions and the subsequent updating of value beliefs. As these processes are affected in a host of psychiatric disorders, our results indicate that pupillometry can be used as an accessible tool to non-invasively study the processes underlying ongoing reinforcement learning in the clinic.

The pupil response under constant illumination can be used as a marker of cognitive processes. In the past, pupillary responses have been studied in the context of arousal and decision-making. However, recent work involving Parkinson's patients suggested that pupillary responses are additionally affected by reward sensitivity. Here, we build on these findings by examining how pupil responses are modulated by reward and loss while participants (N = 30) performed a Pavlovian reversal learning task. In fast (transient) pupil responses, we observed arousal-based influences on pupil size both during the expectation of upcoming value and the evaluation of unexpected monetary outcomes. Importantly, after incorporating eye blink rate (EBR), a behavioral correlate of striatal dopamine levels, we observed that participants with lower EBR showed stronger pupil dilation during the expectation of upcoming reward. Subsequently, when reward expectations were violated, participants with lower EBR showed stronger pupil responses after experiencing unexpected loss. Across trials, the detection of a reward contingency reversal was reflected in a slow (tonic) dilatory pupil response observed already several trials prior to the behavioral report. Interestingly, EBR correlated positively with this tonic detection response, suggesting that variability in the arousal-based detection response may reflect individual differences in striatal dopaminergic tone. Our results provide evidence that a behavioral marker of baseline striatal dopamine level (EBR) can potentially be used to describe the differential effects of value-based learning in the arousal-based pupil response.

The gene rpoN (ntrA, g1nF) encodes an alternative sigma factor, cr5'. In enteric bacteria, c&", also termed RPON, is a positive regulator of expression of glnA (encoding glutamine synthetase) and of the aut, hut, and put operons (encoding amino acid transport and degradative enzymes). The nitrogen fixation (nif) promoters of Klebsiella pneumoniae also require X54-RNA polymerase (RNAP). All promoters recognized by a54-RNAP are characterized by an invariant GG doublet at -24 and a GC doublet at -12 upstream of the transcriptional start site. Recognition complexes between a54-RNAP and the promoter are closed and nonproductive transcriptionally. Isomerization to the productive open complex requires binding of diverse activator proteins >100 nucleotides upstream of the transcription site. In the case of ginA and nifLA of K. pneumoniae, the activator is NTRC (34); in the case of other nif operons, it is NIFA (28, 30).In Rhizobium meliloti, the nitrogen-fixing endosymbiotic bacterium of Medicago sativa, the rpoN locus has been mutated and sequenced (36) and gene expression has been analyzed (2). A mutant formed Fix-alfalfa nodules and could not grow on C4-dicarboxylates, which are likely to be the plant-supplied substrate for nitrogen fixation in indeterminate nodules of alfalfa. The dicarboxylate permease gene (dctA) of R. meliloti has an RPON-RNAP consensus sequence 60 base pairs (bp) upstream of the first ATG and binding sites for the activator proteins DCTD (19) and NIFA (10).NGR (New Guinea Rhizobium) 234 is a broad-host-range strain (45). The rpoN (ntrA) gene of NGR234 has been cloned and mutated; its phenotype was pleiotropic and included a measurable effect on nodulation gene expression. Preliminary analysis of a site-directed interposon mutant, NGR234rnJ, and its minimally complementing subclone pSD23, was reported elsewhere (40). The rnl locus was mapped on the NGR234 chromosome between ade-J and * Corresponding author. his-2 (32). In the present report we provide the nucleotide sequence analysis of rpoN of NGR234. We compare the locus and encoded RPON protein with those of R. meliloti and Pseudomonas putida, which have rpoN genes respectively very homologous and dissimilar to that of NGR234. We also analyze the phenotype of NGR234rn3, a sitedirected mutant carrying an internal deletion in the rpoN coding sequence. We present evidence that the rpoN-encoded alternative sigma factor is required for symbiotic functions: normal nodulation kinetics and determinate nodule organogenesis as well as "late" nodule functions like dicarboxylate tranport and nitrogen fixation. We hypothesize that RPON is a primary coregulator of the endosymbiotic life-style of members of the genus Rhizobium. MATERIALS AND METHODSBacteriology and genetic techniques. Bacterial strains, plasmids, and bacteriophages are described in Table 1. Complex (LB, TY, or YM) and defined (RM) media, growth conditions for Rhizobium strain NGR234R and Escherichia coli, and antibiotic concentrations were as described previously (40). Azotobacter vinelandii...

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Nodule senescence is one aspect of nitrogen fixation that is important to study from the perspective of improving the host-bacteroid interaction. In winged bean nodules, a 21-kilodalton protein is specifically expressed when senescence begins. Using subcellular fractionation, we observed that this plant protein interacts with the bacteroids. Microsequencing of the protein allowed us to obtain a specific oligonucleotide that was used to isolate the corresponding nodule cDNA. Sequence analysis of this cDNA revealed that the 21-kilodalton protein has all of the features of a legume Kunitz protease inhibitor. Subsequent analysis confirmed that this nodulin is indeed a protease inhibitor. lmmunocytochemical study showed that the protease inhibitor is exclusively localized i11 infected senescent cells of the nodule, particularly in disorganized bacteroids, the peribacteroid membrane, vacuole membranes, and in the vacuole fluid. The specific expression of a protease inhibitor at senescence may be of particular interest if the targeted proteolytic activity is important for the symbiotic relationship. This point is discussed in relation to the known nodule proteases.