Acyl-homoserine lactone (AHL) quorum sensing controls gene expression in hundreds of Proteobacteria including a number of plant and animal pathogens. Generally, the AHL receptors are members of a family of related transcription factors, and although they have been targets for development of antivirulence therapeutics there is very little structural information about this class of bacterial receptors. We have determined the structure of the transcription factor, QscR, bound to N-3-oxo-dodecanoyl-homoserine lactone from the opportunistic human pathogen Pseudomonas aeruginosa at a resolution of 2.55 Å. The ligand-bound QscR is a dimer with a unique symmetric “cross-subunit” arrangement containing multiple dimerization interfaces involving both domains of each subunit. The QscR dimer appears poised to bind DNA. Predictions about signal binding and dimerization contacts were supported by studies of mutant QscR proteins in vivo. The acyl chain of the AHL is in close proximity to the dimerization interfaces. Our data are consistent with an allosteric mechanism of signal transmission in the regulation of DNA binding and thus virulence gene expression.

-A fundamental goal of systems neuroscience is to understand the neural mechanisms underlying decision making. The midbrain superior colliculus (SC) is known to be central to the selection of one among many potential spatial targets for movements, which represents an important form of decision making that is tractable to rigorous experimental investigation. In this review, we first discuss data from mammalian models-including primates, cats, and rodents-that inform our understanding of how neural activity in the SC underlies the selection of targets for movements. We then examine the anatomy and physiology of inputs to the SC from three key regions that are themselves implicated in motor decisions-the basal ganglia, parabrachial region, and neocortex-and discuss how they may influence SC activity related to target selection. Finally, we discuss the potential for methodological advances to further our understanding of the neural bases of target selection. Our overarching goal is to synthesize what is known about how the SC and its inputs act together to mediate the selection of targets for movements, to highlight open questions about this process, and to spur future studies addressing these questions.

How movements are selected is a fundamental question in systems neuroscience. While many studies have elucidated the sensorimotor transformations underlying stimulus-guided movements, less is known about how internal goals – critical drivers of goal-directed behavior – guide movements. The basal ganglia are known to bias movement selection according to value, one form of internal goal. Here, we examine whether other internal goals, in addition to value, also influence movements via the basal ganglia. We designed a novel task for mice that dissociated equally rewarded internally-specified and stimulus-guided movements, allowing us to test how each engaged the basal ganglia. We found that activity in the substantia nigra pars reticulata, a basal ganglia output, predictably differed preceding internally-specified and stimulus-guided movements. Incorporating these results into a simple model suggests that internally-specified movements may be facilitated relative to stimulus-guided movements by basal ganglia processing.DOI: http://dx.doi.org/10.7554/eLife.13833.001

Selecting and moving to spatial targets are critical components of goal-directed behavior, yet their neural bases are not well understood. The superior colliculus (SC) is thought to contain a topographic map of contralateral space in which the activity of specific neuronal populations corresponds to particular spatial locations. However, these spatial representations are modulated by several decision-related variables, suggesting that they reflect information beyond simply the location of an upcoming movement. Here, we examine the extent to which these representations arise from competitive spatial choice. We recorded SC activity in male mice performing a behavioral task requiring orienting movements to targets for a water reward in two contexts. In "competitive" trials, either the left or right target could be rewarded, depending on which stimulus was presented at the central port. In "noncompetitive" trials, the same target (e.g., left) was rewarded throughout an entire block. While both trial types required orienting movements to the same spatial targets, only in competitive trials do targets compete for selection. We found that in competitive trials, pre-movement SC activity predicted movement to contralateral targets, as expected. However, in noncompetitive trials, some neurons lost their spatial selectivity and in others activity predicted movement to ipsilateral targets. Consistent with these findings, unilateral optogenetic inactivation of pre-movement SC activity ipsiversively biased competitive, but not noncompetitive, trials. Incorporating these results into an attractor model of SC activity points to

Parkinsonian motor deficits are associated with elevated inhibitory output from the basal ganglia (BG). However, several features of Parkinson's disease (PD) have not been accounted for by this simple "classical rate model" framework, including the observation in PD patients that movements guided by external stimuli are less impaired than otherwise-identical movements generated based on internal goals. Is this difference due to divergent processing within the BG itself, or to the recruitment of extra-BG pathways by sensory processing? In addition, surprisingly little is known about precisely when, in the sequence from selecting to executing movements, BG output is altered by PD. Here, we address these questions by recording activity in the SNr, a key BG output nucleus, in hemiparkinsonian mice performing a well-controlled behavioral task requiring stimulus-guided and internally-specified directional movements. We found that hemiparkinsonian mice exhibited a bias ipsilateral to the side of dopaminergic cell loss that was stronger when movements were internally specified rather than stimulus guided, consistent with clinical observations in parkinsonian patients. We further found that changes in parkinsonian SNr activity during movement preparation were consistent with the ipsilateral behavioral bias, as well as its greater magnitude for internally-specified movements. While these findings are inconsistent with some aspects of the classical rate model, they are accounted for by a related "directional rate model" positing that SNr output phasically over-inhibits motor output in a direction-specific manner. These results suggest that parkinsonian changes in BG output underlying movement preparation contribute to the greater deficit in internally-specified than stimulus-guided movements.