scholarly journals Nucleus accumbens neurons encode initiation and vigor of reward approach behavior

2021 ◽  
Author(s):  
David Levcik ◽  
Adam H. Sugi ◽  
José A. Pochapski ◽  
Gabriel Baltazar ◽  
Laura N. Pulido ◽  
...  

AbstractThe nucleus accumbens (NAc) is considered an interface between motivation and action, with NAc neurons playing an important role in promoting reward approach. However, the encoding by NAc neurons that contribute to this role remains unknown. Here, we trained male rats to find rewards in an 8-arm radial maze. The activity of 62 neurons, mostly in the shell of the NAc, were recorded while rats ran towards each reward place. General linear model (GLM) analysis showed that variables related to the vigor of the locomotor approach, like speed and acceleration, and the fraction of the approach run completed were the best predictors of the firing rate for most NAc neurons. Nearly 23% of the recorded neurons, here named locomotion-off cells, were inhibited during the entire approach run, suggesting that reduction in firing of these neurons promotes initiation of locomotor approach. Another 24% of the neurons presented a peak of activity during acceleration followed by a valley during deceleration (peak-valley cells). Together, these neurons accounted for most of the speed and acceleration encoding identified in the GLM analysis. Cross-correlations between firing and speed indicated that the spikes of peak-valley cells were followed by increases in speed, suggesting that the activity of these neurons drives acceleration. In contrast, a further 19% of neurons presented a valley during acceleration followed by a peak just prior to or after reaching reward (valley-peak cells). These findings suggest that these three classes of NAc neurons control the initiation and vigor of the locomotor approach to reward.Significance StatementDeciphering the mechanisms by which the NAc controls the vigor of motivated behavior is critical to better understand and treat psychiatric conditions in which motivation is dysregulated. Manipulations of the NAc profoundly impair subjects’ ability to spontaneously approach reward-associated locations, preventing them from exerting effort to obtain reward. Here, we identify for the first time specific activity of NAc neurons in relation to spontaneous approach behavior. We discover three classes of neurons that could control initiation of movement and the speed vs. time trajectory during locomotor approach. These results suggest a prominent but heretofore unknown role for the NAc in regulating the kinematics of reward approach locomotion.

Appetite ◽  
2020 ◽  
Vol 153 ◽  
pp. 104739 ◽  
Author(s):  
Danusa Mar Arcego ◽  
Rachel Krolow ◽  
Carine Lampert ◽  
Ana Paula Toniazzo ◽  
Emily dos Santos Garcia ◽  
...  

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Bernadette O'Donovan ◽  
Adewale Adeluyi ◽  
Erin L Anderson ◽  
Robert D Cole ◽  
Jill R Turner ◽  
...  

Deficient motivation contributes to numerous psychiatric disorders, including withdrawal from drug use, depression, schizophrenia, and others. Nucleus accumbens (NAc) has been implicated in motivated behavior, but it remains unclear whether motivational drive is linked to discrete neurobiological mechanisms within the NAc. To examine this, we profiled cohorts of Sprague-Dawley rats in a test of motivation to consume sucrose. We found that substantial variability in willingness to exert effort for reward was not associated with operant responding under low-effort conditions or stress levels. Instead, effort-based motivation was mirrored by a divergent NAc shell transcriptome with differential regulation at potassium and dopamine signaling genes. Functionally, motivation was inversely related to excitability of NAc principal neurons. Furthermore, neuronal and behavioral outputs associated with low motivation were linked to faster inactivation of a voltage-gated potassium channel, Kv1.4. These results raise the prospect of targeting Kv1.4 gating in psychiatric conditions associated with motivational dysfunction.


2021 ◽  
Author(s):  
Alice Servonnet ◽  
Pierre-Paul Rompré ◽  
Anne-Noël Samaha

Reward-associated conditioned stimuli (CS) can acquire predictive value, evoking conditioned approach behaviors that prepare animals to engage with forthcoming rewards. Such CS can also acquire conditioned reinforcing value, becoming attractive and pursued. Through their predictive and conditioned reinforcing properties, CS can promote adaptive (e.g., locating food) but also maladaptive responses (e.g., drug use). Basolateral amygdala neurons projecting to the nucleus accumbens core (BLA→NAc core neurons) mediate the response to appetitive CS, but the extent to which this involves effects on the predictive and/or conditioned reinforcing properties of CS is unclear. Thus, we examined the effects of optogenetic stimulation of BLA→NAc core neurons on conditioned approach behavior and on the instrumental pursuit of a CS, the latter a measure of conditioned reinforcement. Water-restricted, adult male rats learned that a light-tone compound cue (CS) predicts water delivery. Pairing optogenetic stimulation of BLA→NAc core neurons with CS presentation potentiated conditioned approach behavior, and did so even under extinction conditions, when water was omitted. This suggests that BLA→NAc core neurons promote cue-induced expectation of rewards. Rats also received instrumental conditioning sessions during which they could lever press for CS presentations, without water delivery. Optogenetic stimulation of BLA→NAc core neurons either during these instrumental test sessions or during prior CS-water conditioning did not influence lever responding for the CS. This suggests that BLA→NAc core neurons do not influence the conditioned reinforcing effects of CS. We conclude that BLA→NAc core neurons promote cue-induced control over behavior by increasing cue-triggered anticipation of rewards, without influencing cue 'wanting'.


Author(s):  
Aline Byrnes ◽  
Elsa E. Ramos ◽  
Minoru Suzuki ◽  
E.D. Mayfield

Renal hypertrophy was induced in 100 g male rats by the injection of 250 mg folic acid (FA) dissolved in 0.3 M NaHCO3/kg body weight (i.v.). Preliminary studies of the biochemical alterations in ribonucleic acid (RNA) metabolism of the renal tissue have been reported recently (1). They are: RNA content and concentration, orotic acid-c14 incorporation into RNA and acid soluble nucleotide pool, intracellular localization of the newly synthesized RNA, and the specific activity of enzymes of the de novo pyrimidine biosynthesis pathway. The present report describes the light and electron microscopic observations in these animals. For light microscopy, kidney slices were fixed in formalin, embedded, sectioned, and stained with H & E and PAS.


1990 ◽  
Vol 63 (02) ◽  
pp. 286-290 ◽  
Author(s):  
Christina Beurling-Harbury ◽  
Pehr B Harbury

SummaryActin is the major ATP and ADP binding protein in platelets, 0.9–1.3 nmol/108 cells, 50–70% in the unpolymerized state. The goal of these experiments was to develop a method for extracting all protein-bound ATP and ADP from undisturbed platelets in plasma. Extraction of actin-bound ADP is routine while extraction of actin-bound ATP from platelets in buffer has been unsuccessful. Prior to extraction the platelets were exposed to 14-C adenine, to label the metabolic and actin pools of ATP and ADP. The specific activity was determined from the actin-bound ADP in the 43% ethanol precipitate. Sequential ethanol and perchlorate extractions of platelet rich plasma, and the derived supernatants and precipitates were performed. ATP concentrations were determined with the luciferase assay, and radioactive nucleotides separated by TLC. A total of 1.18 nmol/108 cells of protein-bound ATP and ADP was recovered, 52% ATP (0.61 nmol). The recovery of protein-bound ADP was increased from 0.3 to 0.57 nmol/108 cells. This approach for the first time successfully recovered protein bound ATP and ADP from platelets in a concentration expected for actin.


1964 ◽  
Vol 47 (1) ◽  
pp. 51-57 ◽  
Author(s):  
K.-O. Mosebach ◽  
W. Dirscherl

ABSTRACT The initial distribution of radioactive C was studied in the cell fractions of the liver, kidney, testes and thigh muscles after intraperitoneal injection of testosterone-4-14C into 40 day old male rats. To make this possible, the absolute and specific activity values (μc/mg C) were determined. After both ten and twenty minutes the cytoplasm fractions possessed the highest activity values, the only exception being the specific activity of the liver cytoplasm ten minutes after injection when the microsomes of the liver showed a higher activity. After 20 min the mitochondria possessed the highest specific activity values among the corpuscular fractions. The specific activity values in the microsomes of all four organs studied were lower 20 min after the time of injection than after 10 min, a fact, which is suspected to be the result of the initial formation of conjugates in the microsomes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saleem Farooq ◽  
Ruqeya Nazir ◽  
Shabir Ahmad Ganai ◽  
Bashir Ahmad Ganai

AbstractAs an approach to the exploration of cold-active enzymes, in this study, we isolated a cold-active protease produced by psychrotrophic bacteria from glacial soils of Thajwas Glacier, Himalayas. The isolated strain BO1, identified as Bacillus pumilus, grew well within a temperature range of 4–30 °C. After its qualitative and quantitative screening, the cold-active protease (Apr-BO1) was purified. The Apr-BO1 had a molecular mass of 38 kDa and showed maximum (37.02 U/mg) specific activity at 20 °C, with casein as substrate. It was stable and active between the temperature range of 5–35 °C and pH 6.0–12.0, with an optimum temperature of 20 °C at pH 9.0. The Apr-BO1 had low Km value of 1.0 mg/ml and Vmax 10.0 µmol/ml/min. Moreover, it displayed better tolerance to organic solvents, surfactants, metal ions and reducing agents than most alkaline proteases. The results exhibited that it effectively removed the stains even in a cold wash and could be considered a decent detergent additive. Furthermore, through protein modelling, the structure of this protease was generated from template, subtilisin E of Bacillus subtilis (PDB ID: 3WHI), and different methods checked its quality. For the first time, this study reported the protein sequence for psychrotrophic Apr-BO1 and brought forth its novelty among other cold-active proteases.


Author(s):  
Wenjin Xu ◽  
Qingxiao Hong ◽  
Zi Lin ◽  
Hong Ma ◽  
Weisheng Chen ◽  
...  
Keyword(s):  

2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.


2015 ◽  
Vol 26 (3) ◽  
pp. 495-505 ◽  
Author(s):  
Meredith O. Sweeney ◽  
Agnieszka Collins ◽  
Shae B. Padrick ◽  
Bruce L. Goode

Branched actin filament networks in cells are assembled through the combined activities of Arp2/3 complex and different WASP/WAVE proteins. Here we used TIRF and electron microscopy to directly compare for the first time the assembly kinetics and architectures of actin filament networks produced by Arp2/3 complex and dimerized VCA regions of WAVE1, WAVE2, or N-WASP. WAVE1 produced strikingly different networks from WAVE2 or N-WASP, which comprised unexpectedly short filaments. Further analysis showed that the WAVE1-specific activity stemmed from an inhibitory effect on filament elongation both in the presence and absence of Arp2/3 complex, which was observed even at low stoichiometries of WAVE1 to actin monomers, precluding an effect from monomer sequestration. Using a series of VCA chimeras, we mapped the elongation inhibitory effects of WAVE1 to its WH2 (“V”) domain. Further, mutating a single conserved lysine residue potently disrupted WAVE1's inhibitory effects. Taken together, our results show that WAVE1 has unique activities independent of Arp2/3 complex that can govern both the growth rates and architectures of actin filament networks. Such activities may underlie previously observed differences between the cellular functions of WAVE1 and WAVE2.


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