scholarly journals Pupillometry as a reliable metric of auditory detection and discrimination across diverse stimulus paradigms in animal models

2020 ◽  
Author(s):  
Pilar Montes-Lourido ◽  
Manaswini Kar ◽  
Isha Kumbam ◽  
Srivatsun Sadagopan

AbstractEstimates of detection and discrimination thresholds are often used to explore broad perceptual similarities between human subjects and animal models. Pupillometry shows great promise as a non-invasive, easily-deployable method of comparing human and animal thresholds. Using pupillometry, previous studies in animal models have obtained threshold estimates to simple stimuli such as pure tones, but have not explored whether similar pupil responses can be evoked by complex stimuli, what other stimulus contingencies might affect stimulus-evoked pupil responses, and if pupil responses can be modulated by experience or short-term training. In this study, we used an auditory oddball paradigm to estimate detection and discrimination thresholds across a wide range of stimuli in guinea pigs. We demonstrate that pupillometry yields reliable detection and discrimination thresholds across a range of simple (tones) and complex (conspecific vocalizations) stimuli; that pupil responses can be robustly evoked using different stimulus contingencies (low-level acoustic changes, or higher level categorical changes); and that pupil responses are modulated by short-term training. These results lay the foundation for using pupillometry as a high-throughput method of estimating thresholds in large experimental cohorts, and unveil the full potential of using pupillometry to explore broad similarities between humans and animal models.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pilar Montes-Lourido ◽  
Manaswini Kar ◽  
Isha Kumbam ◽  
Srivatsun Sadagopan

AbstractEstimates of detection and discrimination thresholds are often used to explore broad perceptual similarities between human subjects and animal models. Pupillometry shows great promise as a non-invasive, easily-deployable method of comparing human and animal thresholds. Using pupillometry, previous studies in animal models have obtained threshold estimates to simple stimuli such as pure tones, but have not explored whether similar pupil responses can be evoked by complex stimuli, what other stimulus contingencies might affect stimulus-evoked pupil responses, and if pupil responses can be modulated by experience or short-term training. In this study, we used an auditory oddball paradigm to estimate detection and discrimination thresholds across a wide range of stimuli in guinea pigs. We demonstrate that pupillometry yields reliable detection and discrimination thresholds across a range of simple (tones) and complex (conspecific vocalizations) stimuli; that pupil responses can be robustly evoked using different stimulus contingencies (low-level acoustic changes, or higher level categorical changes); and that pupil responses are modulated by short-term training. These results lay the foundation for using pupillometry as a reliable method of estimating thresholds in large experimental cohorts, and unveil the full potential of using pupillometry to explore broad similarities between humans and animal models.


2021 ◽  
Vol 12 ◽  
Author(s):  
Elena Selezneva ◽  
Michael Brosch ◽  
Sanchit Rathi ◽  
T. Vighneshvel ◽  
Nicole Wetzel

Pupil dilation in response to unexpected stimuli has been well documented in human as well as in non-human primates; however, this phenomenon has not been systematically compared between the species. This analogy is also crucial for the role of non-human primates as an animal model to investigate neural mechanisms underlying the processing of unexpected stimuli and their evoked pupil dilation response. To assess this qualitatively, we used an auditory oddball paradigm in which we presented subjects a sequence of the same sounds followed by occasional deviants while we measured their evoked pupil dilation response (PDR). We used deviants (a frequency deviant, a pink noise burst, a monkey vocalization and a whistle sound) which differed in the spectral composition and in their ability to induce arousal from the standard. Most deviants elicited a significant pupil dilation in both species with decreased peak latency and increased peak amplitude in monkeys compared to humans. A temporal Principal Component Analysis (PCA) revealed two components underlying the PDRs in both species. The early component is likely associated to the parasympathetic nervous system and the late component to the sympathetic nervous system, respectively. Taken together, the present study demonstrates a qualitative similarity between PDRs to unexpected auditory stimuli in macaque and human subjects suggesting that macaques can be a suitable model for investigating the neuronal bases of pupil dilation. However, the quantitative differences in PDRs between species need to be investigated in further comparative studies.


2017 ◽  
Author(s):  
Richard E Rosch ◽  
Ryszard Auksztulewicz ◽  
Pui Duen Leung ◽  
Karl J Friston ◽  
Torsten Baldeweg

N-methyl-D-aspartate receptors (NMDARs) are expressed widely throughout the human cortex. Yet disturbances in NMDAR transmission - as implicated in patients with schizophrenia or pharmacologically induced - can cause a regionally specific set of electrophysiological effects. Here, we present a double-blind placebo-controlled study of the effects of the NMDAR blocker ketamine in human volunteers. We employ a marker of auditory learning and putative synaptic plasticity - the mismatch negativity - in a roving auditory oddball paradigm. Using recent advances in Bayesian modelling of group effects in dynamic causal modelling, we fit biophysically plausible network models of the auditory processing hierarchy to whole-scalp evoked response potential recordings. This allowed us to identify the regionally specific effects of ketamine in a distributed network of interacting cortical sources. Under placebo, our analysis replicated previous findings regarding the effects of stimulus repetition and deviance on connectivity within the auditory hierarchy. Crucially, we show that the effect of ketamine is best explained as a selective change in intrinsic inhibition, with a pronounced ketamine-induced reduction of inhibitory interneuron connectivity in frontal sources. These results are consistent with findings from invasive recordings in animal models exposed to NMDAR blockers, and provide evidence that inhibitory-interneuron specific NMDAR dysfunction may be sufficient to explain electrophysiological abnormalities of sensory learning induced by ketamine in human subjects.


PMLA ◽  
2009 ◽  
Vol 124 (2) ◽  
pp. 548-555 ◽  
Author(s):  
Kimberly W. Benston

Of all the beings that are, presumably the most difficult to think about are living creatures, because … they are in a certain way most closely akin to us, and … are at the same time separated from our ek-sistent essence by an abyss.—Heidegger, “Letter on Humanism”Heir to the divided aristotelian vision of nonhuman creatures as, alternately, mute foils (Politics 9; BK. 1, Sec. 2) and behavioral mirrors (Parts 138–39, bk. 2, sec. 4) of “man,” the properly “political” animal, animal studies has displayed uncertainty about how and where to draw species boundaries. Among the provinces of this field of inquiry, none is more defined by this tension than laboratory biomedical research, where physiological correspondences underwrite animal models of human maladies, while presupposed ontological distinctions justify the consignment of nonhuman animals to treatment considered improper for human subjects. Conventionally, those distinctions have centered on a cluster of intellectual capabilities—reasoning, speaking, intending, remembering—the dearth or deficiency of which abrogates the nonhuman's right to dissent and legitimates the human claim of priority. “Animal studies” in this sense, designating a wide range of investigative operations employing nonhuman animal bodies, posits material resemblance and metaphysical incompatibility between researcher and the object of research.


Author(s):  
R.W. Horne

The technique of surrounding virus particles with a neutralised electron dense stain was described at the Fourth International Congress on Electron Microscopy, Berlin 1958 (see Home & Brenner, 1960, p. 625). For many years the negative staining technique in one form or another, has been applied to a wide range of biological materials. However, the full potential of the method has only recently been explored following the development and applications of optical diffraction and computer image analytical techniques to electron micrographs (cf. De Hosier & Klug, 1968; Markham 1968; Crowther et al., 1970; Home & Markham, 1973; Klug & Berger, 1974; Crowther & Klug, 1975). These image processing procedures have allowed a more precise and quantitative approach to be made concerning the interpretation, measurement and reconstruction of repeating features in certain biological systems.


2016 ◽  
Vol 5 (11) ◽  
pp. 5110
Author(s):  
Sartaj Ahmad Allayie ◽  
Mushtaq Ahmed Parray* ◽  
Bilal Ahmad Bhat ◽  
S. Hemalatha

The use of traditional medicines holds a great promise as an easily available source as effective medicinal agents to cure a wide range of ailments among the people particularly in tropical developing countries like India. The present study investigates the qualitative and quantitative analysis of the major bioactive constituents of N. crenulata leaf extracts. The extractive values of aqueous, acetone and chloroform extracts were found to be 11.34, 4.24 and 6.06 respectively. Qualitative phytochemical analysis of these three solvent extracts confirm the presence of Alkaloids, Saponins, Flavonoids and Phenolic compounds in all the three extracts; however, these phytochemicals were more significant in aqueous extract. Quantitative analysis was carried out using TLC method by different solvent system. Amongst various solvent systems, Butanol: acetic acid: water (9: 0.9: 0.1 v/v/v) shows maximum resolution and number of spots produced at long UV (365 nm) and under iodine vapours. The TLC chromatograms constituted different coloured phytochemical compounds with different Rf values. It can be conveniently used to evaluate the quality of different area samples. This indicates that the leaves can be useful for treating different diseases because the therapeutic activity of a plant is due to the presence of particular class of compounds and thus can serve as potential sources of useful drugs in future.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1184
Author(s):  
Armin Mooranian ◽  
Thomas Foster ◽  
Corina M Ionescu ◽  
Daniel Walker ◽  
Melissa Jones ◽  
...  

Introduction: Recent studies in our laboratory have shown that some bile acids, such as chenodeoxycholic acid (CDCA), can exert cellular protective effects when encapsulated with viable β-cells via anti-inflammatory and anti-oxidative stress mechanisms. However, to explore their full potential, formulating such bile acids (that are intrinsically lipophilic) can be challenging, particularly if larger doses are required for optimal pharmacological effects. One promising approach is the development of nano gels. Accordingly, this study aimed to examine biological effects of various concentrations of CDCA using various solubilising nano gel systems on encapsulated β-cells. Methods: Using our established cellular encapsulation system, the Ionic Gelation Vibrational Jet Flow technology, a wide range of CDCA β-cell capsules were produced and examined for morphological, biological, and inflammatory profiles. Results and Conclusion: Capsules’ morphology and topographic characteristics remained similar, regardless of CDCA or nano gel concentrations. The best pharmacological, anti-inflammatory, and cellular respiration, metabolism, and energy production effects were observed at high CDCA and nano gel concentrations, suggesting dose-dependent cellular protective and positive effects of CDCA when incorporated with high loading nano gel.


Minerals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 347
Author(s):  
Carsten Laukamp ◽  
Andrew Rodger ◽  
Monica LeGras ◽  
Heta Lampinen ◽  
Ian C. Lau ◽  
...  

Reflectance spectroscopy allows cost-effective and rapid mineral characterisation, addressing mineral exploration and mining challenges. Shortwave (SWIR), mid (MIR) and thermal (TIR) infrared reflectance spectra are collected in a wide range of environments and scales, with instrumentation ranging from spaceborne, airborne, field and drill core sensors to IR microscopy. However, interpretation of reflectance spectra is, due to the abundance of potential vibrational modes in mineral assemblages, non-trivial and requires a thorough understanding of the potential factors contributing to the reflectance spectra. In order to close the gap between understanding mineral-diagnostic absorption features and efficient interpretation of reflectance spectra, an up-to-date overview of major vibrational modes of rock-forming minerals in the SWIR, MIR and TIR is provided. A series of scripts are proposed that allow the extraction of the relative intensity or wavelength position of single absorption and other mineral-diagnostic features. Binary discrimination diagrams can assist in rapidly evaluating mineral assemblages, and relative abundance and chemical composition of key vector minerals, in hydrothermal ore deposits. The aim of this contribution is to make geologically relevant information more easily extractable from reflectance spectra, enabling the mineral resources and geoscience communities to realise the full potential of hyperspectral sensing technologies.


Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 673
Author(s):  
Alexandra L. Whittaker ◽  
Yifan Liu ◽  
Timothy H. Barker

The Mouse Grimace Scale (MGS) was developed 10 years ago as a method for assessing pain through the characterisation of changes in five facial features or action units. The strength of the technique is that it is proposed to be a measure of spontaneous or non-evoked pain. The time is opportune to map all of the research into the MGS, with a particular focus on the methods used and the technique’s utility across a range of mouse models. A comprehensive scoping review of the academic literature was performed. A total of 48 articles met our inclusion criteria and were included in this review. The MGS has been employed mainly in the evaluation of acute pain, particularly in the pain and neuroscience research fields. There has, however, been use of the technique in a wide range of fields, and based on limited study it does appear to have utility for pain assessment across a spectrum of animal models. Use of the method allows the detection of pain of a longer duration, up to a month post initial insult. There has been less use of the technique using real-time methods and this is an area in need of further research.


1997 ◽  
Vol 3 (S2) ◽  
pp. 81-82
Author(s):  
M.P. Goheen ◽  
M.S. Bartlett ◽  
M.M. Shaw ◽  
S.R. Meshnick ◽  
J.W. Smith

Pneumocystis carinii pneumonia (PCP) occurs at some time in most patients with acquired immunodeficiency syndrome (AIDS). Trimethoprim/sulfamethoxazole or pentamidine isothionate are the traditional modes of therapy for treatment and prophylaxis of PCP. Unfortunately these drugs are associated with a significant incidence of adverse side effects particularly in patients with AIDS. Toxicity and a growing concern that P. carinii strains are becoming resistant to these compounds is providing the impetus for the search for additional drugs to combat P. carinii. Atovaquone, developed as an antimalarial agent, has activity against a wide range of other organisms, including Toxoplasma sp. and P. carinii, with a lower incidence of adverse reactions during clinical trials. Atovaquone inhibits mitochondrial respiration in P. falciparum and P. carinii. In this study transmission electron microscopy (TEM) was used to observe the effects of atovaquone on P. carinii organisms in short term spinner flask culture.Spinner flask cultures of human embryonic lung cells were inoculated with P. carinii from infected rat lung.


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