scholarly journals High-yield methods for accurate two-alternative visual psychophysics in head-fixed mice

2016 ◽  
Author(s):  
Christopher P Burgess ◽  
Armin Lak ◽  
Nicholas A Steinmetz ◽  
Peter Zatka-Haas ◽  
Charu Bai Reddy ◽  
...  

Research in neuroscience relies increasingly on the mouse, a mammalian species that affords unparalleled genetic tractability and brain atlases. Here we introduce high-yield methods for probing mouse visual decisions. Mice are head-fixed, which facilitates repeatable visual stimulation, eye tracking, and brain access. They turn a steering wheel to make two-alternative choices, forced or unforced. Learning is rapid thanks to intuitive coupling of stimuli to wheel position. The mouse decisions deliver high-quality psychometric curves for detection and discrimination, and conform to the predictions of a simple probabilistic observer model. The task is readily paired with two-photon imaging of cortical activity. Optogenetic inactivation reveals that the task requires the visual cortex. Mice are motivated to perform the task by fluid reward or optogenetic stimulation of dopaminergic neurons. This stimulation elicits larger number of trials and faster learning. These methods provide a platform to accurately probe mouse vision and its neural basis.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoko Kato ◽  
Harumi Katsumata ◽  
Ayumu Inutsuka ◽  
Akihiro Yamanaka ◽  
Tatsushi Onaka ◽  
...  

AbstractMultiple sequential actions, performed during parental behaviors, are essential elements of reproduction in mammalian species. We showed that neurons expressing melanin concentrating hormone (MCH) in the lateral hypothalamic area (LHA) are more active in rodents of both sexes when exhibiting parental nursing behavior. Genetic ablation of the LHA-MCH neurons impaired maternal nursing. The post-birth survival rate was lower in pups born to female mice with congenitally ablated MCH neurons under control of tet-off system, exhibiting reduced crouching behavior. Virgin female and male mice with ablated MCH neurons were less interested in pups and maternal care. Chemogenetic and optogenetic stimulation of LHA-MCH neurons induced parental nursing in virgin female and male mice. LHA-MCH GABAergic neurons project fibres to the paraventricular hypothalamic nucleus (PVN) neurons. Optogenetic stimulation of PVN induces nursing crouching behavior along with increasing plasma oxytocin levels. The hypothalamic MCH neural relays play important functional roles in parental nursing behavior in female and male mice.


2016 ◽  
Vol 22 (2) ◽  
pp. 164-179 ◽  
Author(s):  
Maki S. Koyama ◽  
Adriana Di Martino ◽  
Francisco X. Castellanos ◽  
Erica J. Ho ◽  
Enitan Marcelle ◽  
...  

AbstractObjectives: Clinical neuroscience is increasingly turning to imaging the human brain for answers to a range of questions and challenges. To date, the majority of studies have focused on the neural basis of current psychiatric symptoms, which can facilitate the identification of neurobiological markers for diagnosis. However, the increasing availability and feasibility of using imaging modalities, such as diffusion imaging and resting-state fMRI, enable longitudinal mapping of brain development. This shift in the field is opening the possibility of identifying predictive markers of risk or prognosis, and also represents a critical missing element for efforts to promote personalized or individualized medicine in psychiatry (i.e., stratified psychiatry). Methods: The present work provides a selective review of potentially high-yield populations for longitudinal examination with MRI, based upon our understanding of risk from epidemiologic studies and initial MRI findings. Results: Our discussion is organized into three topic areas: (1) practical considerations for establishing temporal precedence in psychiatric research; (2) readiness of the field for conducting longitudinal MRI, particularly for neurodevelopmental questions; and (3) illustrations of high-yield populations and time windows for examination that can be used to rapidly generate meaningful and useful data. Particular emphasis is placed on the implementation of time-appropriate, developmentally informed longitudinal designs, capable of facilitating the identification of biomarkers predictive of risk and prognosis. Conclusions: Strategic longitudinal examination of the brain at-risk has the potential to bring the concepts of early intervention and prevention to psychiatry. (JINS, 2016, 22, 164–179)


2016 ◽  
Vol 115 (2) ◽  
pp. 1043-1062 ◽  
Author(s):  
Arani Roy ◽  
Jason J. Osik ◽  
Neil J. Ritter ◽  
Shen Wang ◽  
James T. Shaw ◽  
...  

Many circuits in the mammalian brain are organized in a topographic or columnar manner. These circuits could be activated—in ways that reveal circuit function or restore function after disease—by an artificial stimulation system that is capable of independently driving local groups of neurons. Here we present a simple custom microscope called ProjectorScope 1 that incorporates off-the-shelf parts and a liquid crystal display (LCD) projector to stimulate surface brain regions that express channelrhodopsin-2 (ChR2). In principle, local optogenetic stimulation of the brain surface with optical projection systems might not produce local activation of a highly interconnected network like the cortex, because of potential stimulation of axons of passage or extended dendritic trees. However, here we demonstrate that the combination of virally mediated ChR2 expression levels and the light intensity of ProjectorScope 1 is capable of producing local spatial activation with a resolution of ∼200–300 μm. We use the system to examine the role of cortical activity in the experience-dependent emergence of motion selectivity in immature ferret visual cortex. We find that optogenetic cortical activation alone—without visual stimulation—is sufficient to produce increases in motion selectivity, suggesting the presence of a sharpening mechanism that does not require precise spatiotemporal activation of the visual system. These results demonstrate that optogenetic stimulation can sculpt the developing brain.


2016 ◽  
Vol 201 (4) ◽  
pp. 239-252 ◽  
Author(s):  
Sonja E. Lobo ◽  
Luciano César P.C. Leonel ◽  
Carla M.F.C. Miranda ◽  
Talya M. Coelho ◽  
Guilherme A.S. Ferreira ◽  
...  

The placenta is a temporal, dynamic and diverse organ with important immunological features that facilitate embryonic and fetal development and survival, notwithstanding the fact that several aspects of its formation and function closely resemble tumor progression. Placentation in mammals is commonly used to characterize the evolution of species, including insights into human evolution. Although most placentas are discarded after birth, they are a high-yield source for the isolation of stem/progenitor cells and are rich in extracellular matrix (ECM), representing an important resource for regenerative medicine purposes. Interactions among cells, ECM and bioactive molecules regulate tissue and organ generation and comprise the foundation of tissue engineering. In the present article, differences among several mammalian species regarding the placental types and classifications, phenotypes and potency of placenta-derived stem/progenitor cells, placental ECM components and current placental ECM applications were reviewed to highlight their potential clinical and biomedical relevance.


2015 ◽  
Vol 1767 ◽  
pp. 65-74
Author(s):  
Pascal G. Lacroix ◽  
Isabelle Malfant

ABSTRACTRuthenium-nitrosyl (RuII(NO)) complexes are stable in the dark, but exhibit a unique photoreactivity which can lead either to a solid state isomerization from RuII(NO) to RuII(ON), or to a nitric oxide (NO·) release in solution. From our recent discovery of a high yield of isomerization (> 92%) in [RuII(py)4Cl(NO)](PF6)2, we have developed a computational strategy aimed at designing switchable nonlinear optical (NLO) material with high contrast (large difference in the on / off NLO response) in the solid state. Our synthetic targets are terpyridine based RuII chromophores in which various substituents can be introduced to adjust the NLO response which, at best, should be vanishing in the off state. Alternatively, these complexes can undergo a photo-induced NO· release in solution, a possibility which becomes increasingly appealing in relation to the discovery of the numerous biological roles of NO·, in the context of the emergence of the photodynamic therapy. A promising fluorene-terpyridine RuII(NO) complex was investigated, which could find an additional interest in relation to its capability for releasing NO· by a two-photon absorption process.


2017 ◽  
Vol 49 ◽  
pp. 85-97
Author(s):  
Bo Pang ◽  
Xiang Xi Meng ◽  
Yang Long Hou ◽  
Hong Fang Sun ◽  
Qiu Shi Ren

The synthesis of anisotropic branched gold nanoparticles remines to be challenging as their arm number and arm length could hardly be controlled, greatly limited their biomedical application. We report the large-scale high-yield synthesis of PdCu@Au tripods, and, for the first time, their two-photon luminescence properties with quantitative characterization of the two-photon action cross section as well as quantum yield. By introducing nitrogen protection to the synthesis of the PdCu bimetallic cores, this approach eliminates the oxidative etching caused by oxygen in the air, providing a 2.5 times higher synthetic yield of 70.4 %, which enables the large-scale preparation of PdCu@Au at ca. 380 mg per batch. By the conformal coating of PdCu bimetallic cores, the PdCu@Au tripods are prepared with a purity of >90 % with average arm length 45.3 ± 5.6 nm that is ideal for biomedical applications. The PdCu@Au tripods demonstrate a much brighter two-photon luminescence than that from Au nanorods, with a 3.6 ± 0.9 times larger two-photon action cross section and comparable quantum yield. Our result also shows the two-photon luminescence property of PdCu@Au tripods could be tuned by their distinct localized surface plasmon resonance property and, in turn, the different amount of Au coating. This tunability could be explained by the recently-proposed two-step excitation mechanism of two-photon luminescence in Au nanoparticle. The folate-targeted in vitro two-photon luminescence imaging of MDA-MB-435 breast cancer cells were also demonstrated to show the great potential using PdCu@Au tripods as novel multi-functional platforms for cancer theranostics.


2018 ◽  
Author(s):  
Jackson J. Cone ◽  
Megan D. Scantlen ◽  
Mark H. Histed ◽  
John H.R. Maunsell

SummaryWhile recent work has revealed how different inhibitory interneurons influence cortical responses to sensory stimuli, little is known about how their activity contributes to sensory perception. Here, we optogenetically stimulated different genetically defined interneurons (parvalbumin (PV), somatostatin (SST), vasoactive intestinal peptide (VIP)) in visual cortex (V1) of mice working at threshold in contrast increment or decrement detection tasks. The visual stimulus was paired with optogenetic stimulation to assess how enhancing V1 inhibitory neuron activity synchronously during cortical responses altered task performance. PV or SST activation impaired, while VIP stimulation improved, contrast increment detection. Notably, PV or SST stimulation also impaired contrast decrement detection, when opsin-evoked inhibition would exaggerate stimulus-evoked decrements in firing rate, and thus might improve performance. The impairment produced by PV or SST stimulation persisted throughout many weeks of testing. In contrast mice learned to reliably detect VIP activation in the absence of natural visual stimulation. Thus, different inhibitory signals make distinct contributions to visual contrast perception.


2019 ◽  
Vol 6 (6) ◽  
pp. 181904 ◽  
Author(s):  
Friederike G. S. Zimmermann ◽  
Xiaoqian Yan ◽  
Bruno Rossion

Humans may be the only species able to rapidly and automatically recognize a familiar face identity in a crowd of unfamiliar faces, an important social skill. Here, by combining electroencephalography (EEG) and fast periodic visual stimulation (FPVS), we introduce an ecologically valid, objective and sensitive neural measure of this human individual face recognition function. Natural images of various unfamiliar faces are presented at a fast rate of 6 Hz, allowing one fixation per face, with variable natural images of a highly familiar face identity, a celebrity, appearing every seven images (0.86 Hz). Following a few minutes of stimulation, a high signal-to-noise ratio neural response reflecting the generalized discrimination of the familiar face identity from unfamiliar faces is observed over the occipito-temporal cortex at 0.86 Hz and harmonics. When face images are presented upside-down, the individual familiar face recognition response is negligible, being reduced by a factor of 5 over occipito-temporal regions. Differences in the magnitude of the individual face recognition response across different familiar face identities suggest that factors such as exposure, within-person variability and distinctiveness mediate this response. Our findings of a biological marker for fast and automatic recognition of individual familiar faces with ecological stimuli open an avenue for understanding this function, its development and neural basis in neurotypical individual brains along with its pathology. This should also have implications for the use of facial recognition measures in forensic science.


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