The superior colliculus is a conserved sensorimotor structure that integrates visual and other sensory information to drive reflexive behaviors. Although the evidence for this is strong and ...compelling, a number of experiments reveal a role for the superior colliculus in behaviors usually associated with the cerebral cortex, such as attention and decision-making. Indeed, in addition to collicular outputs targeting brainstem regions controlling movements, the superior colliculus also has ascending projections linking it to forebrain structures including the basal ganglia and amygdala, highlighting the fact that the superior colliculus, with its vast inputs and outputs, can influence processing throughout the neuraxis. Today, modern molecular and genetic methods combined with sophisticated behavioral assessments have the potential to make significant breakthroughs in our understanding of the evolution and conservation of neuronal cell types and circuits in the superior colliculus that give rise to simple and complex behaviors.
Basso et al. provide a new look at the superior colliculus. Focusing on classic and recent work, the review highlights how the colliculus is positioned to affect much of the neuraxis and plays key roles in both simple and complex behaviors.
The superior colliculus is one of the most well-studied structures in the brain, and with each new report, its proposed role in behavior seems to increase in complexity. Forty years of evidence show ...that the colliculus is critical for reorienting an organism toward objects of interest. In monkeys, this involves saccadic eye movements. Recent work in the monkey colliculus and in the homologous optic tectum of the bird extends our understanding of the role of the colliculus in higher mental functions, such as attention and decision making. In this review, we highlight some of these recent results, as well as those capitalizing on circuit-based methodologies using transgenic mice models, to understand the contribution of the colliculus to attention and decision making. The wealth of information we have about the colliculus, together with new tools, provides a unique opportunity to obtain a detailed accounting of the neurons, circuits, and computations that underlie complex behavior.
Simple decisions arise from the evaluation of sensory evidence. But decisions are determined by more than just evidence. Individuals establish internal decision criteria that influence how they ...respond. Where or how decision criteria are established in the brain remains poorly understood. Here, we show that neuronal activity in the superior colliculus (SC) predicts changes in decision criteria. Using a novel “Yes-No” task that isolates changes in decision criterion from changes in decision sensitivity, and computing neuronal measures of sensitivity and criterion, we find that SC neuronal activity correlates with the decision criterion regardless of the location of the choice report. We also show that electrical manipulation of activity within the SC produces changes in decisions consistent with changes in decision criteria and are largely independent of the choice report location. Our correlational and causal results together provide strong evidence that SC activity signals the position of a decision criterion.
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•Priming changes monkey’s decision criteria without changing decision sensitivity•SC neuronal activity correlates with decision criteria•Stimulation of the SC produces reliable shifts in monkeys’ decision criteria•Stimulation-induced shifts are largely independent of saccades
Crapse et al. describe neuronal activity in the superior colliculus correlating with decision criteria, rather than a decision variable. Manipulation of SC neuronal activity with microstimulation changed the criterion predictably, demonstrating a causal role for the SC in decision criteria.
Perceptual decisions arise after considering the available sensory evidence 1. When sensory information is unreliable, a good strategy is to rely on previous experience in similar situations to guide ...decisions 2–6. It is well known that patients with Parkinson’s disease (PD) are impaired at value-based decision-making 7–11. How patients combine past experience and sensory information to make perceptual decisions is unknown. We developed a novel, perceptual decision-making task and manipulated the statistics of the sensory stimuli presented to patients with PD and healthy participants to determine the influence of past experience on decision-making. We show that patients with PD are impaired at combining previously learned information with current sensory information to guide decisions. We modeled the results using the drift-diffusion model (DDM) and found that the impairment corresponds to a failure in adjusting the amount of sensory evidence needed to make a decision. Our modeling results also show that two complementary mechanisms operate to implement a bias when two sets of priors are learned concurrently. Asymmetric decision threshold adjustments, as reflected by changes in the starting point of evidence accumulation, are responsible for a general choice bias, whereas the adjustment of a dynamic bias that develops over the course of a trial, as reflected by a drift-rate offset, provides the stimulus-specific component of the prior. A proper interplay between these two processes is required to implement a bias based on concurrent, stimulus-specific priors in decision-making. We show here that patients with PD are impaired in these across-trial decision threshold adjustments.
•Patients are impaired at combining priors and sensory information under uncertainty•Patients fail to adjust their decision threshold•Patients with Parkinson’s disease can learn priors from feedback•Drift-rate offset mediates stimulus-specific bias in perceptual decision-making
Perugini et al. show that patients with Parkinson’s disease are impaired when combining prior experience with available sensory information to guide decisions. This deficit results from a failure to adjust the amount of sensory evidence needed to make a decision.
•Identifying the international standards for research ethics and regulations concerning non-human primates (NHPs).•Introduction of an international animal welfare and use committee ...(IAWUC).•Implementation of standards for animal welfare and care in research facilitates global collaboration efforts.•International collaborations can improve the standards of animal welfare and care.•Transparency in scientific research with NHPs influences public opinion and aids in public engagement.
Scientific excellence is a necessity for progress in biomedical research. As research becomes ever more international, establishing international collaborations will be key to advancing our scientific knowledge. Understanding the similarities in standards applied by different nations to animal research, and where the differences might lie, is crucial. Cultural differences and societal values will also contribute to these similarities and differences between countries and continents. Our overview is not comprehensive for all species, but rather focuses on non-human primate (NHP) research, involving New World marmosets and Old World macaques, conducted in countries where NHPs are involved in neuroimaging research. Here, an overview of the ethics and regulations is provided to help assess welfare standards amongst primate research institutions. A comparative examination of these standards was conducted to provide a basis for establishing a common set of standards for animal welfare. These criteria may serve to develop international guidelines, which can be managed by an International Animal Welfare and Use Committee (IAWUC). Internationally, scientists have a moral responsibility to ensure excellent care and welfare of their animals, which in turn, influences the quality of their research. When working with animal models, maintaining a high quality of care (“culture of care”) and welfare is essential. The transparent promotion of this level of care and welfare, along with the results of the research and its impact, may reduce public concerns associated with animal experiments in neuroscience research.
Recent studies suggest that neurons in sensorimotor circuits involved in perceptual decision-making also play a role in decision confidence. In these studies, confidence is often considered to be an ...optimal readout of the probability that a decision is correct. However, the information leading to decision accuracy and the report of confidence often covaried, leaving open the possibility that there are actually two dissociable signal types in the brain: signals that correlate with decision accuracy (optimal confidence) and signals that correlate with subjects’ behavioral reports of confidence (subjective confidence). We recorded neuronal activity from a sensorimotor decision area, the superior colliculus (SC) of monkeys, while they performed two different tasks. In our first task, decision accuracy and confidence covaried, as in previous studies. In our second task, we implemented a motion discrimination task with stimuli that were matched for decision accuracy but produced different levels of confidence, as reflected by behavioral reports. We used a multivariate decoder to predict monkeys’ choices from neuronal population activity. As in previous studies on perceptual decision-making mechanisms, we found that neuronal decoding performance increased as decision accuracy increased. However, when decision accuracy was matched, performance of the decoder was similar between high and low subjective confidence conditions. These results show that the SC likely signals optimal decision confidence similar to previously reported cortical mechanisms, but is unlikely to play a critical role in subjective confidence. The results also motivate future investigations to determine where in the brain signals related to subjective confidence reside.
Minthostachys verticillata (Griseb.) Epling (Lamiaceae), known as Peperina is a medicinal native plant, with a traditional use as a digestive, antispasmodic and antidiarrheic.
Despite its folkloric ...use, no scientific evaluation of this plant related to the gastrointestinal inflammatory process has been carried out to date. The present study aims to assess the effects of M. verticillata on gastrointestinal system in experimental models.
M. verticillata (250 and 500 mg/kg) was orally tested in a colitis model induced by acetic acid. Colon weight/length ratio, oxidative stress (oxidized and reduced glutathione), histological changes using Alcian blue and hematoxylin & eosin staining and expression of IL1β, TNFα, iNOS, COX-2 were evaluated. The effect of the extract in three additional in vivo models were studied: intestinal motility and diarrhea induced by ricin oil, and visceral pain induced by intracolonic administration of capsaicin. Finally, the activity on concentration response curves of acetylcholine, calcium chloride, potassium and serotonin were achieved in isolated rat jejunum.
In the colitis model, M. verticillata induced a significant reduction in the colon weight/length ratio, oxidative stress and expression levels of IL-1β, iNOS and COX-2. Also, the extract diminished the severity of microscopic tissue damage and showed protective effect on goblet cells. Intestinal motility, diarrhea, visceral pain-related behaviors and referred hyperalgesia were significantly reduced when the animals were treated with the extract. Furthermore, in isolated jejunum, M. verticillata significantly reduced the contraction induced by serotonin and acetylcholine. Likewise, the extract non-competitively inhibited the response-concentration induced by CaCl2 and inhibited both low and high K+-induced contractions.
This is the first study to validate traditional use of M. verticillata for digestive disorders and demonstrated that its aqueous extract could represent a promising strategy in targeting the multifactorial pathophysiology of inflammatory bowel disease.
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Abstract There has been a dramatic increase in the identification of non-canonical translation and a significant expansion of the protein-coding genome. Among the strategies used to identify ...unannotated small Open Reading Frames (smORFs) that encode microproteins, Ribosome profiling (Ribo-Seq) is the gold standard for the annotation of novel coding sequences by reporting on smORF translation. In Ribo-Seq, ribosome-protected footprints (RPFs) that map to multiple genomic sites are removed since they cannot be unambiguously assigned to a specific genomic location. Furthermore, RPFs necessarily result in short (25-34 nucleotides) reads, increasing the chance of multi-mapping alignments, such that smORFs residing in these regions cannot be identified by Ribo-Seq. Moreover, it has been challenging to identify protein evidence for Ribo-Seq. To solve this, we developed Rp3, a pipeline that integrates proteogenomics and Ribosome profiling to provide unambiguous evidence for a subset of microproteins missed by current Ribo-Seq pipelines. Here, we show that Rp3 maximizes proteomics detection and confidence of microprotein-encoding smORFs.
The Raf family includes three members, of which B-Raf is frequently mutated in melanoma and other tumors. We show that Raf-1 and A-Raf require Hsp90 for stability, whereas B-Raf does not. In ...contrast, mutated, activated B-Raf binds to an Hsp90-cdc37 complex, which is required for its stability and function. Exposure of melanoma cells and tumors to the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in the degradation of mutant B-Raf, inhibition of mitogen-activated protein kinase activation and cell proliferation, induction of apoptosis, and antitumor activity. These data suggest that activated mutated B-Raf proteins are incompetent for folding in the absence of Hsp90, thus suggesting that the chaperone is required for the clonal evolution of melanomas and other tumors that depend on this mutation. Hsp90 inhibition represents a therapeutic strategy for the treatment of melanoma.
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