scholarly journals Opposing contributions of GABAergic and glutamatergic ventral pallidal neurons to motivational behaviours

2019 ◽  
Author(s):  
Marcus Stephenson-Jones ◽  
Christian Bravo-Rivera ◽  
Sandra Ahrens ◽  
Alessandro Furlan ◽  
Carolina Fernandes-Henriques ◽  
...  
Keyword(s):  
Internal State ◽  
Behavioural Response ◽  
Ventral Pallidum ◽  
Approach And Avoidance ◽  
Reward Seeking ◽  
Two Populations ◽  
Control Behaviour ◽  
Motivational Conflict

ABSTRACTThe ventral pallidum (VP) is critical for invigorating reward seeking and is also involved in punishment avoidance, but how it contributes to such opposing behavioural actions remains unclear. Here we show that GABAergic and glutamatergic VP neurons selectively control behaviour in opposing motivational contexts. In vivo recording combined with optogenetics in mice revealed that these two populations oppositely encode positive and negative motivational value, are differentially modulated by animal’s internal state and determine the behavioural response during motivational conflict. Furthermore, GABAergic VP neurons are essential for movements towards reward in a positive motivational context, but suppress movements in an aversive context. In contrast, glutamatergic VP neurons are essential for movements to avoid a threat but suppress movements in an appetitive context. Our results indicate that GABAergic and glutamatergic VP neurons encode the drive for approach and avoidance, respectively, with the balance between their activities determining the type of motivational behaviour.

scholarly journals Coordinated prefrontal state transition leads extinction of reward-seeking behaviors

2020 ◽  
Author(s):  
Eleonora Russo ◽  
Tianyang Ma ◽  
Rainer Spanagel ◽  
Daniel Durstewitz ◽  
Hazem Toutounji ◽  
...  
Keyword(s):  
Single Unit ◽  
Internal State ◽  
Conditioned Reward ◽  
Conditioned Stimuli ◽  
Extinction Learning ◽  
Experimental Conditions ◽  
Reward Seeking ◽  
And Behavior ◽  
Unit Coordination

ABSTRACTExtinction learning suppresses conditioned reward responses and is thus fundamental to adapt to changing environmental demands and to control excessive reward seeking. The medial prefrontal cortex (mPFC) monitors and controls conditioned reward responses. Using in vivo multiple single-unit recordings of mPFC we studied the relationship between single-unit and population dynamics during different phases of an operant conditioning task. To examine the fine temporal relation between neural activity and behavior, we developed a model-based statistical analysis that captured behavioral idiosyncrasies. We found that single-unit responses to conditioned stimuli changed throughout the course of a session even under stable experimental conditions and consistent behavior. However, when behavioral responses to task contingencies had to be updated during the extinction phase, unit-specific modulations became coordinated across the whole population, pushing the network into a new stable attractor state. These results show that extinction learning is not associated with suppressed mPFC responses to conditioned stimuli, but is driven by single-unit coordination into population-wide transitions of the animal’s internal state.

scholarly journals Calcium functional imaging with high-resolution CT in the inner ear

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hisaya Tanioka ◽  
Sayaka Tanioka
Keyword(s):  
Internal State ◽  
Texture Synthesis ◽  
Biological Information ◽  
Endolymphatic Sac ◽  
Otolith Organs ◽  
Synthesis Algorithm ◽  
Utricular Macula ◽  
Positional Vertigo ◽  
Paroxysmal Positional Vertigo

AbstractAlthough the otolith and otolith organs correlate with vertigo and instability, there is no method to investigate them without harmful procedures. We will create the technique for 3D microanatomical images of them, and investigate the in vivo internal state and metabolisms. The otolith and otolith organs images were reconstructed from a texture synthesis algorithm under the skull volume rendering algorithm using a cutting-plane method. The utricular macula was elongated pea-shaped. The saccular macula was almost bud-shaped. The changes in the amount of CaCO3 in the maculae and the endolymphatic sac showed various morphologies, reflecting the balance status of each subject. Both shapes and volumes were not always constant depending on time. In Meniere’s disease (MD), the saccular macula was larger and the utricular macula was smaller. In benign paroxysmal positional vertigo (BPPV), the otolith increased in the utricular macula but did not change much in the saccular macula. The saccule, utricle, and endolymphatic sac were not constantly shaped according to their conditions. These created 3D microanatomical images can allow detailed observations of changes in physiological and biological information. This imaging technique will contribute to our understanding of pathology and calcium metabolism in the in vivo vestibulum.

scholarly journals Circuit-dependent striatal PKA and ERK signaling underlies rapid behavioral shift in mating reaction of male mice

2015 ◽  
Vol 112 (21) ◽  
pp. 6718-6723 ◽  
Author(s):  
Akihiro Goto ◽  
Ichiro Nakahara ◽  
Takashi Yamaguchi ◽  
Yuji Kamioka ◽  
Kenta Sumiyama ◽  
...  
Keyword(s):  
D2 Receptor ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Signaling Cascades ◽  
Male Mice ◽  
Indirect Pathway ◽  
Dynamic Activity ◽  
Reward Seeking ◽  
Electric Shocks

The selection of reward-seeking and aversive behaviors is controlled by two distinct D1 and D2 receptor-expressing striatal medium spiny neurons, namely the direct pathway MSNs (dMSNs) and the indirect pathway MSNs (iMSNs), but the dynamic modulation of signaling cascades of dMSNs and iMSNs in behaving animals remains largely elusive. We developed an in vivo methodology to monitor Förster resonance energy transfer (FRET) of the activities of PKA and ERK in either dMSNs or iMSNs by microendoscopy in freely moving mice. PKA and ERK were coordinately but oppositely regulated between dMSNs and iMSNs by rewarding cocaine administration and aversive electric shocks. Notably, the activities of PKA and ERK rapidly shifted when male mice became active or indifferent toward female mice during mating behavior. Importantly, manipulation of PKA cascades by the Designer Receptor recapitulated active and indifferent mating behaviors, indicating a causal linkage of a dynamic activity shift of PKA and ERK between dMSNs and iMSNs in action selection.

scholarly journals Design of a biochemical circuit motif for learning linear functions

2014 ◽  
Vol 11 (101) ◽  
pp. 20140902 ◽  
Author(s):  
Matthew R. Lakin ◽  
Amanda Minnich ◽  
Terran Lane ◽  
Darko Stefanovic
Keyword(s):  
Internal State ◽  
Linear Functions ◽  
Learning Performance ◽  
Adaptive Behaviour ◽  
Biological Processes ◽  
Biochemical System ◽  
Biochemical Systems ◽  
Robustness To Noise ◽  
Novel Design

Learning and adaptive behaviour are fundamental biological processes. A key goal in the field of bioengineering is to develop biochemical circuit architectures with the ability to adapt to dynamic chemical environments. Here, we present a novel design for a biomolecular circuit capable of supervised learning of linear functions, using a model based on chemical reactions catalysed by DNAzymes. To achieve this, we propose a novel mechanism of maintaining and modifying internal state in biochemical systems, thereby advancing the state of the art in biomolecular circuit architecture. We use simulations to demonstrate that the circuit is capable of learning behaviour and assess its asymptotic learning performance, scalability and robustness to noise. Such circuits show great potential for building autonomous in vivo nanomedical devices. While such a biochemical system can tell us a great deal about the fundamentals of learning in living systems and may have broad applications in biomedicine (e.g. autonomous and adaptive drugs), it also offers some intriguing challenges and surprising behaviours from a machine learning perspective.

scholarly journals Autoradiographic Study on the Origin and Fate of Small Lymphoid Cells in the Dog Bone Marrow: Effect of Femoral Artery Clamping during in Vivo Availability of H3-Thymidine

Blood ◽  
1964 ◽  
Vol 24 (3) ◽  
pp. 254-266 ◽  
Author(s):  
G. KEISER ◽  
H. COTTIER ◽  
N. ODARTCHENKO ◽  
V. P. BOND
Keyword(s):  
Bone Marrow ◽  
Femoral Artery ◽  
Blood Stream ◽  
Autoradiographic Study ◽  
Precursor Cells ◽  
Lymphoid Cells ◽  
The Other ◽  
Dog Bone ◽  
Two Populations

Abstract The origin and fate of small lymphoid cells in the dog bone marrow were studied autoradiographically by observing the effect of clamping of the femoral artery during in vivo availability of H3-thymidine. Heavily labeled small lymphoid cells appeared in the bone marrow of the clamped leg 3 hours after injection of the tracer and increased in number up to 6 days. The labeling indices of these cells, however, were significantly lower than those of control marrow. A possible interpretation is that dog bone marrow contains two populations of small lymphoid cells, one migrating into the marrow via the blood stream, the other originating from local precursor cells within the marrow. There was no evidence for a transformation of migrated small lymphoid cells into erythroblasts during the first 48 hours after injection of H3-thymidine.

scholarly journals Age-dependent emergence of neurophysiological and behavioral abnormalities in progranulin-deficient mice

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Dávid Nagy ◽  
Lauren Herl Martens ◽  
Liza Leventhal ◽  
Angela Chen ◽  
Craig Kelley ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Neurodegenerative Disorder ◽  
Neuronal Loss ◽  
Loss Of Function ◽  
Behavioral Alterations ◽  
Response Latencies ◽  
Reward Seeking ◽  
Behavioral Abnormalities ◽  
Age Dependent

Abstract Background Loss-of-function mutations in the progranulin gene cause frontotemporal dementia, a genetic, heterogeneous neurodegenerative disorder. Progranulin deficiency leads to extensive neuronal loss in the frontal and temporal lobes, altered synaptic connectivity, and behavioral alterations. Methods The chronological emergence of neurophysiological and behavioral phenotypes of Grn heterozygous and homozygous mice in the dorsomedial thalamic—medial prefrontal cortical pathway were evaluated by in vivo electrophysiology and reward-seeking/processing behavior, tested between ages 3 and 12.5 months. Results Electrophysiological recordings identified a clear age-dependent deficit in the thalamocortical circuit. Both heterozygous and homozygous mice exhibited impaired input-output relationships and paired-pulse depression, but evoked response latencies were only prolonged in heterozygotes. Furthermore, we demonstrate firstly an abnormal reward-seeking/processing behavior in the homozygous mice which correlates with previously reported neuroinflammation. Conclusion Our findings indicate that murine progranulin deficiency causes age-dependent neurophysiological and behavioral abnormalities thereby indicating their validity in modeling aspects of human frontotemporal dementia.

scholarly journals Only a small population of adult Sertoli cells actively proliferates in culture

Reproduction ◽  
2016 ◽  
Vol 152 (4) ◽  
pp. 271-281 ◽  
Author(s):  
Andrey Yu Kulibin ◽  
Ekaterina A Malolina
Keyword(s):  
Sertoli Cells ◽  
Collagen Matrix ◽  
Transitional Zone ◽  
Small Population ◽  
Seminiferous Tubules ◽  
Differentiated Cells ◽  
Low Levels ◽  
Two Populations

Adult mammalian Sertoli cells (SCs) have been considered to be quiescent terminal differentiated cells for many years, but recently, proliferation of adult SCs was demonstrated in vitro and in vivo. We further examined mouse SC behavior in culture and found that there are two populations of adult SCs. The first population is SCs from seminiferous tubules that hardly proliferate in vitro. The second population is small and consists of SCs with atypical nuclear morphology from the terminal segments of seminiferous tubules, a transitional zone (TZ). TZ SCs multiply in culture and form colonies, display mixture of mature and immature SC characteristics, and generate cord-like structures in a collagen matrix. The specific features of TZ SCs are ACTA2 expression in vitro and DMRT1 low levels in vivo and in vitro. Although the in vivo function of TZ SCs still remains unclear, this finding has significant implications for our understanding of SC differentiation and functioning in adult mammals.

scholarly journals Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic Response

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Pazit Y. Cohen ◽  
Raphael Breuer ◽  
Philip Zisman ◽  
Shulamit B. Wallach-Dayan
Keyword(s):  
Mouse Lung ◽  
Genetic Changes ◽  
Abnormal Accumulation ◽  
Inflammatory Milieu ◽  
The Impact ◽  
Mouse Lungs ◽  
Two Populations ◽  
Deficient Mice ◽  
Chip Analysis

Lung fibrosis is characterized by abnormal accumulation of fibroblasts in the interstitium of the alveolar space. Two populations of myofibroblasts, distinguished by Thy1 expression, are detected in human and murine lungs. Accumulation of Thy1-negative (Thy1−) myofibroblasts was shown in the lungs of humans with idiopathic pulmonary fibrosis (IPF) and of bleomycin-treated mice. We aimed to identify genetic changes in lung myofibroblasts following Thy1 crosslinking and assess the impact of specific lung myofibroblast Thy1-deficiency, in vivo, in bleomycin-injured mouse lungs. Thy1 increased in mouse lung lymphocytes following bleomycin injury but decreased in myofibroblasts when fibrosis was at the highest point (14 days), as assessed by immunohistochemistry. Using gene chip analysis, we detected that myofibroblast Thy1 crosslinking mediates downregulation of genes promoting cell proliferation, survival, and differentiation, and reduces production of extracellular matrix (ECM) components, while concurrently mediating the upregulation of genes known to foster inflammation and immunological functions. Chimeric Thy1-deficient mice with Thy1+lymphocytes and Thy1−myofibroblasts showed fibrosis similar to wild-type mice and an increased number of CD4/CD25 regulatory T cells, with a concomitant decrease in inflammation. Lung myofibroblasts downregulate Thy1 expression to increase their proliferation but to diminish the in vivo inflammatory milieu. Inflammation is not essential for evolution of fibrosis as was previously stated.

scholarly journals Greater striatopallidal adaptive coding during cue-reward learning and food reward habituation predict future weight gain

2017 ◽  
Author(s):  
Kyle Stanley Burger
Keyword(s):  
Weight Gain ◽  
Food Reward ◽  
Animal Experiments ◽  
Reward Learning ◽  
Ventral Pallidum ◽  
Palatable Food ◽  
Growth Curve Models ◽  
Simultaneous Decrease ◽  
Dopamine Signaling

Animal experiments indicate that after repeated pairings of palatable food receipt and cues that predict palatable food receipt, dopamine signaling increases in response to predictive cues, but decreases in response to food receipt. Using functional MRI and mixed effects growth curve models with 35 females (M age=15.5±0.9; M BMI=24.5±5.4) we documented an increase in BOLD response in the caudate (r=.42) during exposure to cues predicting impending milkshake receipt over repeated exposures, demonstrating a direct measure of in vivo cue-reward learning in humans. Further, we observed a simultaneous decrease in putamen (r=-.33) and ventral pallidum (r=-.45) response during milkshake receipt that occurred over repeated exposures, putatively reflecting food reward habitation. We then tested whether cue-reward learning and habituation slopes predicted future weight over 2-year follow-up. Those who exhibited the greatest escalation in ventral pallidum responsivity to cues and the greatest decrease in caudate response to milkshake receipt showed significantly larger increases in BMI (r=.39 and -.69 respectively). Interestingly, cue-reward learning propensity and food reward habituation were not correlated, implying that these factors may constitute qualitatively distinct vulnerability pathways to excess weight gain. These two individual difference factors may provide insight as to why certain people have shown obesity onset in response to the current obesogenic environment in western cultures, whereas others have not.

scholarly journals SOX-2 Mediated Conversion of Astrocyte to Neuron

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Brady Tucker ◽  
Wei Wu ◽  
Xiao-Ming Xu
Keyword(s):  
Functional Recovery ◽  
Axonal Regeneration ◽  
Spontaneous Recovery ◽  
Treatment Groups ◽  
Behavioral Studies ◽  
Significant Difference ◽  
Contusion Injury ◽  
One Step ◽  
Two Populations

Background: Axonal regeneration following SCI is crucial if individuals are to avoid permanent neurological damage. A plausible solution to circumvent neuronal death/ axonal degeneration may be in the conversion of ubiquitously distributed astrocytes into neurons. Previous research has shown that the neuronal transcription factor SOX-2 has the potential to convert mature glial cells into neuroblasts (iANBs). Furthermore, iANBs possess the capability to differentiate into functional neurons. Our study employs an in vivo mouse model to demonstrate the functional recovery that SOX-2 mediated conversion of astrocytes to neurons may pose following SCI.    Methods: Our study utilized two populations of mice. The first population received thoracic T10 contusion injuries while the second population received cervical C5 dorsal hemi-sections. Mice were subsequently blindly categorized into groups A, B, and C (treatment groups) depending on which injection they would be receiving: LV-hNG2-GFP, LV-hNG2-SOX2, or LV-p75-2. Following injection, behavioral studies including Hargreaves, roto-rod, grid walk, BMS (contusion mice) and pellet retrieval (DH mice) were performed to assess functional recovery at 2 week intervals.  Results: The astrocyte conversion to neuron project spans more than 16 weeks. Here we present data obtained in the first eight weeks which includes behavioral analyses of contusion injury mice. Currently grid walk, BMS, and Hargreaves testing show similar trends in spontaneous recovery however no significant difference is observed between the independent injection groups. On the contrary roto-rod analyses showed injection group C had a significantly lower latency to fall time in comparison to groups A and B six weeks post injection (wpi).  Conclusion: The treatments are hypothesized to not take effect until approximately 8 wpi thus we expect subsequent behavioral testing to reveal significant differences between treatment groups, ultimately taking one step closer towards therapeutic intervention following traumatic SCI.  

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