scholarly journals Optogenetic interrogation of the role of striatal patches in habit formation and inhibition of striatal dopamine

2020 ◽  
Author(s):  
J.A. Nadel ◽  
S.S. Pawelko ◽  
J.R. Scott ◽  
R. McLaughlin ◽  
M. Fox ◽  
...  
Keyword(s):  
Habit Formation ◽  
Dorsal Striatum ◽  
Fast Scan Cyclic Voltammetry ◽  
Reward Seeking ◽  
Surrounding Matrix ◽  
Dopamine Signaling ◽  
Potential Interactions ◽  
Insight Into

AbstractHabits are inflexible behaviors that can be maladaptive in diseases including drug addiction. The striatum is integral to habit formation, and interspersed throughout the striatum are patches, or striosomes, which are characterized by unique gene expression relative to the surrounding matrix. Recent work has indicated that patches are necessary for habit formation, but how patches contribute to habits remains partially understood. Here, using optogenetics, we modulated striatal patches in Sepw1-NP67 mice during habit formation. We find that patch activation during operant training impairs habit formation, and conversely, that acute patch stimulation after reward devaluation can drive habitual reward seeking. Patch stimulation invigorates general locomotion but is not inherently rewarding. Finally, we use fast-scan cyclic voltammetry to demonstrate that patch stimulation suppresses dopamine release in dorsal striatum in vivo. Overall, this work provides novel insight into the role of the patch compartment in habit formation, and potential interactions with dopamine signaling.

scholarly journals Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
J. A. Nadel ◽  
S. S. Pawelko ◽  
J. R. Scott ◽  
R. McLaughlin ◽  
M. Fox ◽  
...  
Keyword(s):  
Dopamine Release ◽  
Habit Formation ◽  
Dorsal Striatum ◽  
Variable Interval ◽  
Interval Training ◽  
Substantia Nigra Pars Compacta ◽  
Fast Scan Cyclic Voltammetry ◽  
Surrounding Matrix ◽  
Dopamine Signaling ◽  
Habitual Responding

AbstractHabits are inflexible behaviors that develop after extensive repetition, and overreliance on habits is a hallmark of many pathological states. The striatum is involved in the transition from flexible to inflexible responding, and interspersed throughout the striatum are patches, or striosomes, which make up ~15% of the volume of the striatum relative to the surrounding matrix compartment. Previous studies have suggested that patches are necessary for normal habit formation, but it remains unknown exactly how patches contribute to habit formation and expression. Here, using optogenetics, we stimulated striatal patches in Sepw1-NP67 mice during variable interval training (VI60), which is used to establish habitual responding. We found that activation of patches at reward retrieval resulted in elevated responding during VI60 training by modifying the pattern of head entry and pressing. Further, this optogenetic manipulation reduced subsequent responding following reinforcer devaluation, suggesting modified habit formation. However, patch stimulation did not generally increase extinction rates during a subsequent extinction probe, but did result in a small ‘extinction burst’, further suggesting goal-directed behavior. On the other hand, this manipulation had no effect in omission trials, where mice had to withhold responses to obtain rewards. Finally, we utilized fast-scan cyclic voltammetry to investigate how patch activation modifies evoked striatal dopamine release and found that optogenetic activation of patch projections to the substantia nigra pars compacta (SNc) is sufficient to suppress dopamine release in the dorsal striatum. Overall, this work provides novel insight into the role of the patch compartment in habit formation, and provides a potential mechanism for how patches modify habitual behavior by exerting control over dopamine signaling.

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

scholarly journals In vivo evidence for the unique kinetics of evoked dopamine release in the patch and matrix compartments of the striatum

2021 ◽  
Author(s):  
Andrea Jaquins-Gerstl ◽  
Kathryn M. Nesbitt ◽  
Adrian C. Michael
Keyword(s):  
Dopamine Release ◽  
Spatial Organization ◽  
Dorsal Striatum ◽  
Immunohistochemical Analysis ◽  
Extensive Literature ◽  
Fast Scan Cyclic Voltammetry ◽  
Medial Dorsal ◽  
The Matrix ◽  
Slow Kinetic

AbstractThe neurochemical transmitter dopamine (DA) is implicated in a number of diseases states, including Parkinson’s disease, schizophrenia, and drug abuse. DA terminal fields in the dorsal striatum and core region of the nucleus accumbens in the rat brain are organized as heterogeneous domains exhibiting fast and slow kinetic of DA release. The rates of dopamine release are significantly and substantially faster in the fast domains relative to the slow domains. The striatum is composed of a mosaic of spatial compartments known as the striosomes (patches) and the matrix. Extensive literature exists on the spatial organization of the patch and matrix compartments and their functions. However, little is known about these compartments as they relate to fast and slow kinetic DA domains observed by fast scan cyclic voltammetry (FSCV). Thus, we combined high spatial resolution of FSCV with detailed immunohistochemical analysis of these architectural compartments (patch and matrix) using fluorescence microscopy. Our findings demonstrated a direct correlation between patch compartments with fast domain DA kinetics and matrix compartments to slow domain DA kinetics. We also investigated the kinetic domains in two very distinct sub-regions in the striatum, the lateral dorsal striatum (LDS) and the medial dorsal striatum (MDS). The lateral dorsal striatum as opposed to the medial dorsal striatum is mainly governed by fast kinetic DA domains. These finding are highly relevant as they may hold key promise in unraveling the fast and slow kinetic DA domains and their physiological significance. Graphical abstract

scholarly journals Dissemination of Rat Cytomegalovirus through Infected Granulocytes and Monocytes In Vitro and In Vivo

2003 ◽  
Vol 77 (20) ◽  
pp. 11274-11278 ◽  
Author(s):  
B. W. A. van der Strate ◽  
J. L. Hillebrands ◽  
S. S. Lycklama à Nijeholt ◽  
L. Beljaars ◽  
C. A. Bruggeman ◽  
...  
Keyword(s):  
Intravenous Injection ◽  
Systemic Infection ◽  
Insight Into

ABSTRACT The role of leukocytes in the in vivo dissemination of cytomegalovirus was studied in this experiment. Rat cytomegalovirus (RCMV) could be transferred to rat granulocytes and monocytes by cocultivation with RCMV-infected fibroblasts in vitro. Intravenous injection of purified infected granulocytes or monocytes resulted in a systemic infection in rats, indicating that our model is a powerful tool to gain further insight into CMV dissemination and the development of new antivirals.

A Novel Insight into the Role of Entry Tears in Type B Aortic Dissection: Pressure Measurements in an in Vitro Model

2017 ◽  
Vol 40 (10) ◽  
pp. 563-574 ◽  
Author(s):  
Stefania Marconi ◽  
Ettore Lanzarone ◽  
Hector De Beaufort ◽  
Michele Conti ◽  
Santi Trimarchi ◽  
...  
Keyword(s):  
False Lumen ◽  
Patient Characteristics ◽  
Acute Type ◽  
Type B ◽  
Type B Dissection ◽  
Vitro Model ◽  
Insight Into

Introduction Predicting aortic growth in acute type B dissection is fundamental in planning interventions. Several factors are considered to be growth predictors in the literature and, among them, size and location of entry tears have been recognized to particularly influence the false lumen pressure. In this study, we develop an in vitro setting to analyze the actual impact of size and location of the entry tears on false lumen pressure, in the absence of other confounding factors such as the deformability of the aortic wall. Methods We formalize some indexes that synthetically describe the false lumen pressure with respect to the true lumen pressure. Then, we experimentally derive their values in several configurations of the in vitro setting, and we look for trends in the indexes with respect to the size and location of entry tears. Results: Results show that the tears have a relevant impact on the false lumen pressure, but that their size and location alone are not enough to explain the phenomena observed in vivo. Conclusions To predict the behavior of acute type B dissection, we therefore recommend not limiting to size and location, as many effects may derive from the interactions between these parameters and other patient characteristics.

scholarly journals Modified Sawhorse Waveform for the Voltammetric Detection of Oxytocin

2022 ◽  
Author(s):  
Favian Liu ◽  
Negar Ghasem Ardabili ◽  
Izaiah Brown ◽  
Harmain Rafi ◽  
Clarice Cook ◽  
...  
Keyword(s):  
Brain Slices ◽  
Physiological Role ◽  
Peptide Hormone ◽  
Protective Effects ◽  
Fast Scan Cyclic Voltammetry ◽  
The Past ◽  
Voltammetric Detection ◽  
Carbon Fiber Microelectrodes

Abstract Carbon fiber microelectrodes (CFMEs) have been used to detect neurotransmitters and other biomolecules using fast-scan cyclic voltammetry (FSCV) for the past few decades. This technique measures neurotransmitters such as dopamine and, more recently, physiologically relevant neuropeptides. Oxytocin, a pleiotropic peptide hormone, is physiologically important for adaptation, development, reproduction, and social behavior. This neuropeptide functions as a stress-coping molecule, an anti-inflammatory agent, and serves as an antioxidant with protective effects especially during adversity or trauma. Here, we measure tyrosine using the Modified Sawhorse Waveform (MSW), enabling enhanced electrode sensitivity for the amino acid and oxytocin peptide. Applying the MSW, decreased surface fouling and enabled codetection with other monoamines. As oxytocin contains tyrosine, the MSW was also used to detect oxytocin. The sensitivity of oxytocin detection was found to be 3.99 ± 0.49 nA/µM, (n=5). Additionally, we demonstrate that applying the MSW on CFMEs allows for real time measurements of exogenously applied oxytocin on rat brain slices. These studies may serve as novel assays for oxytocin detection in a fast, sub-second timescale with possible implications for in vivo measurements and further understanding of the physiological role of oxytocin.

scholarly journals A selective effect of dopamine on information-seeking

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Valentina Vellani ◽  
Lianne P de Vries ◽  
Anne Gaule ◽  
Tali Sharot
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Information Seeking ◽  
Selective Effect ◽  
Reward Seeking ◽  
The Impact ◽  
The Brain ◽  
Insight Into ◽  
Primary Reward

Humans are motivated to seek information from their environment. How the brain motivates this behavior is unknown. One speculation is that the brain employs neuromodulatory systems implicated in primary reward-seeking, in particular dopamine, to instruct information-seeking. However, there has been no causal test for the role of dopamine in information-seeking. Here, we show that administration of a drug that enhances dopamine function (dihydroxy-L-phenylalanine; L-DOPA) reduces the impact of valence on information-seeking. Specifically, while participants under Placebo sought more information about potential gains than losses, under L-DOPA this difference was not observed. The results provide new insight into the neurobiology of information-seeking and generates the prediction that abnormal dopaminergic function (such as in Parkinson’s disease) will result in valence-dependent changes to information-seeking.

scholarly journals Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Brianna J. Klein ◽  
Suk Min Jang ◽  
Catherine Lachance ◽  
Wenyi Mi ◽  
Jie Lyu ◽  
...  
Keyword(s):  
Posttranslational Modification ◽  
Memory Impairment ◽  
Target Genes ◽  
Epigenetic Mark ◽  
Mechanistic Insight ◽  
Genomic Analyses ◽  
Insight Into

Abstract Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning and memory impairment, yet our understanding of this epigenetic mark remains insufficient. Here, we identify the native MORF complex as a histone H3K23-specific acetyltransferase and elucidate its mechanism of action. The acetyltransferase function of the catalytic MORF subunit is positively regulated by the DPF domain of MORF (MORFDPF). The crystal structure of MORFDPF in complex with crotonylated H3K14 peptide provides mechanistic insight into selectivity of this epigenetic reader and its ability to recognize both histone and DNA. ChIP data reveal the role of MORFDPF in MORF-dependent H3K23 acetylation of target genes. Mass spectrometry, biochemical and genomic analyses show co-existence of the H3K23ac and H3K14ac modifications in vitro and co-occupancy of the MORF complex, H3K23ac, and H3K14ac at specific loci in vivo. Our findings suggest a model in which interaction of MORFDPF with acylated H3K14 promotes acetylation of H3K23 by the native MORF complex to activate transcription.

scholarly journals Understanding the Role of Shape and Composition of Star-Shaped Polymers and their Ability to Both Bind and Prevent Bacteria Attachment on Oral Relevant Surfaces

2019 ◽  
Vol 10 (4) ◽  
pp. 56 ◽  
Author(s):  
Hamid Mortazavian ◽  
Guillaume A. Picquet ◽  
Jānis Lejnieks ◽  
Lynette A. Zaidel ◽  
Carl P. Myers ◽  
...  
Keyword(s):  
Bacterial Adhesion ◽  
Oral Care ◽  
Oral Bacteria ◽  
New Material ◽  
Polymer Shape ◽  
Dental Applications ◽  
Insight Into ◽  
Structural Aspects

In this study, we have prepared a series of 4- and 6-arm star-shaped polymers with varying molecular weight and hydrophobicity in order to provide insight into the role and relationship that shape and composition have on the binding and protecting of oral relevant surfaces (hydroxyapatite, HAP) from bacteria colonization. Star-shaped acrylic acid polymers were prepared by free-radical polymerization in the presence of chain transfer agents with thiol groups, and their binding to the HAP surfaces and subsequent bacteria repulsion was measured. We observed that binding was dependent on both polymer shape and hydrophobicity (star vs. linear), but their relative efficacy to reduce oral bacteria attachment from surfaces was dependent on their hydrophobicity only. We further measured the macroscopic effects of these materials to modify the mucin-coated HAP surfaces through contact angle experiments; the degree of angle change was dependent on the relative hydrophobicity of the materials suggesting future in vivo efficacy. The results from this study highlight that star-shaped polymers represent a new material platform for the development of dental applications to control bacterial adhesion which can lead to tooth decay, with various compositional and structural aspects of materials being vital to effectively design oral care products.

scholarly journals Sensitization of Rapid Dopamine Signaling in the Nucleus Accumbens Core and Shell After Repeated Cocaine in Rats

2010 ◽  
Vol 104 (2) ◽  
pp. 922-931 ◽  
Author(s):  
Nii A. Addy ◽  
David P. Daberkow ◽  
Jeremy N. Ford ◽  
Paul A. Garris ◽  
R. Mark Wightman
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Release ◽  
Cocaine Exposure ◽  
Sprague Dawley ◽  
Nucleus Accumbens Core ◽  
Fast Scan Cyclic Voltammetry ◽  
Uptake Inhibition ◽  
Sprague Dawley Rats ◽  
Dopamine Signaling

Repeated cocaine exposure and withdrawal leads to long-term changes, including behavioral and dopamine sensitization to an acute cocaine challenge, that are most pronounced after long withdrawal periods. However, the changes in dopamine neurotransmission after short withdrawal periods are less well defined. To study dopamine neurotransmission after 1-day withdrawal, we used fast-scan cyclic voltammetry (FSCV) to determine whether repeated cocaine alters rapid dopamine release and uptake in the nucleus accumbens (NAc) core and shell. FSCV was performed in urethane anesthetized male Sprague-Dawley rats that had previously received one or seven daily injections of saline or cocaine (15 mg/kg, ip). In response to acute cocaine, subjects showed increased dopamine overflow that resulted from both increased dopamine release and slowed dopamine uptake. One-day cocaine pre-exposure, however, did not alter dopaminergic responses to a subsequent cocaine challenge. In contrast, 7-day cocaine-treated subjects showed a potentiated rapid dopamine response in both the core and shell after an acute cocaine challenge. In addition, kinetic analysis during the cocaine challenge showed a greater increase in apparent Km of 7-day cocaine exposed subjects. Together, the data provide the first in vivo demonstration of rapid dopamine sensitization in the NAc core and shell after a short withdrawal period. In addition, the data clearly delineate cocaine's release and uptake effects and suggest that the observed sensitization results from greater uptake inhibition in cocaine pre-exposed subjects.

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