scholarly journals Characterization of striatal dopamine projections across striatal subregions in behavioral flexibility

2021 ◽  
Author(s):  
R.K. van der Merwe ◽  
J.A. Nadel ◽  
D. Copes-Finke ◽  
S. Pawelko ◽  
J.S. Scott ◽  
...  
Keyword(s):  
Dopamine Release ◽  
Dynamic Environment ◽  
Behavioral Flexibility ◽  
Reversal Task ◽  
Causative Mechanism ◽  
Extended Training ◽  
Contingency Reversal ◽  
Striatal Function ◽  
Dorsomedial Striatum

AbstractBehavioral flexibility is key to survival in a dynamic environment. While flexible, goal-directed behaviors are initially dependent on dorsomedial striatum, they become dependent on lateral striatum with extended training as behaviors become inflexible. Similarly, dopamine release shifts from ventromedial to lateral striatum across learning, and impairment of lateral dopamine release disrupts habitual, inflexible responding. This raises the possibility that lateral dopamine release is a causative mechanism in establishing inflexible behaviors late in training, though this has not been directly tested. Here, we utilized optogenetics to activate dopamine terminals in dorsal medial (DMS), dorsal lateral (DLS), and ventral (NAc) striatum in DATcre mice to determine how specific dopamine subpopulations impact behavioral flexibility. Mice performed a reversal task in which they self-stimulated DMS, DLS, or NAc dopamine terminals by pressing one of two levers before action-outcome lever contingencies were reversed. Consistent with presumed ventromedial/lateral striatal function, we found that mice self-stimulating ventromedial dopamine terminals rapidly reversed lever preference following contingency reversal, while mice self-stimulating dopamine terminals in DLS showed impaired reversal learning. These impairments were characterized by more regressive errors and reliance on lose-stay strategies following reversal, suggesting reward insensitivity and overreliance on previously learned actions. This study supports a model of striatal function in which dorsomedial dopamine facilitates goal-directed responding, and dorsolateral dopamine release is a key mechanism in supporting the transition toward inflexible behaviors.

scholarly journals Prepubertal ovariectomy alters dorsomedial striatum indirect pathway neuron excitability and explore/exploit balance in female mice

2021 ◽  
Author(s):  
Kristen Delevich ◽  
Christopher D. Hall ◽  
Linda Wilbrecht
Keyword(s):  
Behavioral Flexibility ◽  
Intrinsic Excitability ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Reversal Task ◽  
Female Mice ◽  
Sham Surgery ◽  
Hormonal Modulation ◽  
Choice Policy ◽  
Dorsomedial Striatum

Decision-making circuits are modulated across life stages (e.g. juvenile, adolescent, or adult)—as well as on the shorter timescale of reproductive cycles in females—to meet changing environmental and physiological demands. Ovarian hormonal modulation of relevant neural circuits is a potential mechanism by which behavioral flexibility is regulated in females. Here we examined the influence of prepubertal ovariectomy (pOVX) versus sham surgery on performance in an odor-based multiple choice reversal task. We observed that pOVX females made different types of errors during reversal learning compared to sham surgery controls. Using reinforcement learning models fit to trial-by-trial behavior, we found that pOVX females exhibited lower inverse temperature parameter (β) compared to sham females. These findings suggest that OVX females solve the reversal task using a more exploratory choice policy, whereas sham females use a more exploitative policy prioritizing estimated high value options. To seek a neural correlate of this behavioral difference, we performed whole-cell patch clamp recordings within the dorsomedial striatum (DMS), a region implicated in regulating action selection and explore/exploit choice policy. We found that the intrinsic excitability of dopamine receptor type 2 (D2R) expressing indirect pathway spiny projection neurons (iSPNs) was significantly higher in pOVX females compared to both unmanipulated and sham surgery females. Finally, to test whether mimicking this increase in iSPN excitability could recapitulate the pattern of reversal task behavior observed in pOVX females, we chemogenetically activated DMS D2R(+) neurons within intact female mice. We found that chemogenetic activation increased exploratory choice during reversal, similar to the pattern we observed in pOVX females. Together, these data suggest that pubertal status may influence explore/exploit balance in females via the modulation of iSPN intrinsic excitability within the DMS.

Striatal low-threshold spiking interneurons locally gate dopamine during learning

2020 ◽  
Author(s):  
Elizabeth N. Holly ◽  
M. Felicia Davatolhagh ◽  
Rodrigo A. España ◽  
Marc V. Fuccillo
Keyword(s):  
Cyclic Voltammetry ◽  
Dopamine Release ◽  
Striatal Dopamine ◽  
Operant Learning ◽  
Fast Scan Cyclic Voltammetry ◽  
Directed Learning ◽  
Low Threshold ◽  
Dorsomedial Striatum

Low-threshold spiking interneurons (LTSIs) in the dorsomedial striatum are potent modulators of goal-directed learning. Here, we uncover a novel function for LTSIs in locally and directly gating striatal dopamine, using in vitro fast scan cyclic voltammetry as well as in vivo GRAB-DA sensor imaging and pharmacology during operant learning. We demonstrate that LTSIs, acting via GABAB signaling, attenuate dopamine release, thereby serving as local coordinators of striatal plasticity.

scholarly journals Further Characterization of Dopamine Release by Permeabilized PC 12 Cells

1987 ◽  
Vol 49 (3) ◽  
pp. 764-770 ◽  
Author(s):  
Gudrun Ahnert-Hilger ◽  
Manfred Gratzl
Keyword(s):  
Dopamine Release ◽  
Pc 12 Cells

scholarly journals Differential dopamine release by psychosis-generating and non-psychosis-generating addictive substances in the nucleus accumbens and dorsomedial striatum

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Klara Danielsson ◽  
Rosita Stomberg ◽  
Louise Adermark ◽  
Mia Ericson ◽  
Bo Söderpalm
Keyword(s):  
Drug Abuse ◽  
Nucleus Accumbens ◽  
Dopamine Release ◽  
Negative Symptoms ◽  
Positive Symptoms ◽  
Differential Effects ◽  
Double Probe ◽  
Dorsomedial Striatum ◽  
Da Release

AbstractSchizophrenia is associated with three main categories of symptoms; positive, negative and cognitive. Of these, only the positive symptoms respond well to treatment with antipsychotics. Due to the lack of effect of antipsychotics on negative symptoms, it has been suggested that while the positive symptoms are related to a hyperdopaminergic state in associative striatum, the negative symptoms may be a result of a reduced dopamine (DA) activity in the nucleus accumbens (nAc). Drug abuse is common in schizophrenia, supposedly alleviating negative symptomatology. Some, but not all, drugs aggravate psychosis, tentatively due to differential effects on DA activity in striatal regions. Here this hypothesis was tested in rats by using a double-probe microdialysis technique to simultaneously assess DA release in the nAc and associative striatum (dorsomedial striatum; DMS) following administration of the psychosis-generating substances amphetamine (0.5 mg/kg), cocaine (15 mg/kg) and Δ9-tetrahydrocannabinol (THC, 3 mg/kg), and the generally non-psychosis-generating substances ethanol (2.5 g/kg), nicotine (0.36 mg/kg) and morphine (5 mg/kg). The data show that amphetamine and cocaine produce identical DA elevations both in the nAc and DMS, whereas nicotine increases DA in nAc only. Ethanol and morphine both increased DMS DA, but weaker and in a qualitatively different way than in nAc, suggesting that the manner in which DA is increased might be important to the triggering of psychosis. THC elevated DA in neither region, indicating that the pro-psychotic effects of THC are not related to DA release. We conclude that psychosis-generating substances affect striatal DA release differently than non-psychosis-generating substances.

scholarly journals Testing Late Bronze Age mobility in southern Sweden in the light of a new multi-proxy strontium isotope baseline of Scania

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250279
Author(s):  
Pernille Ladegaard-Pedersen ◽  
Serena Sabatini ◽  
Robert Frei ◽  
Kristian Kristiansen ◽  
Karin Margarita Frei
Keyword(s):  
Surface Water ◽  
Material Culture ◽  
Bronze Age ◽  
Human Mobility ◽  
Dynamic Environment ◽  
Strontium Isotope ◽  
Late Bronze Age ◽  
Long Distance ◽  
The North

The Bronze Age of Sweden’s southernmost region, Scania, is complex and intriguing. One could say that Scania represented in many ways a gateway for people, ideas and material culture connecting continental Europe with Sweden. Shedding light on the dynamics of human mobility in this region requires an in depth understanding of the local archaeological contexts across time. In this study, we present new archaeological human data from the Late Bronze Age Simris II site, located in an area of Scania showing a dynamic environment throughout the Late Bronze Age, thus likely involving various forms of mobility. Because the characterization of solid strontium isotope baselines is vital for delineating human mobility in prehistory using the strontium isotope methodology, we introduce the first environmentally based multi-proxy (surface water-, plant- and soil leachates) strontium isotope baselines for sub-regions of Scania. Our results show, that the highly complex and spatially scattered lithologies characterising Scania does not allow for a spatially meaningful, geology-based grouping of multi-proxy data that could be beneficial for provenance studies. Instead, we propose sub-regional baselines for areas that don’t necessarily fully correspond and reflect the immediate distribution of bedrock lithologies. Rather than working with a Scania-wide multi-proxy baseline, which we define as 87Sr/86Sr = 0.7133 ± 0.0059 (n = 102, 2σ), we propose sub-regional, multi-proxy baselines as follows: Area 1, farthest to the north, by 87Sr/86Sr = 0.7184 ± 0.0061 (n = 16, 2σ); Area 2, comprising the mid and western part of Scania, with 87Sr/86Sr = 0.7140 ± 0.0043 (n = 48, 2σ); Area 3–4, roughly corresponding to a NW-SE trending zone dominated by horst-graben tectonics across Scania, plus the carbonate dominated south western part of Scania with 87Sr/86Sr = 0.7110 ± 0.0030 (n = 39, 2σ). Our results also reflect that the complexity of the geology of Scania requires systematic, high density, statistically sound sampling of multiple proxies to adequately constrain the baseline ranges, particularly of those areas dominated by Precambrian lithologies. The averaging effect of biosphere Sr in surface water might be beneficial for the characterization of baselines in such terranes. Our sub-regional, area-specific baselines allow for a first comparison of different baseline construction strategies (single-proxy versus multi-proxy; Scania-wide versus sub-regional). From the Late Bronze Age Simris II site, we identified six individuals that could be analysed for Sr isotopes, to allow for an interpretation of their provenance using the newly established, environmental strontium isotope baselines. All but one signature agrees with the local baselines, including the 87Sr/86Sr value we measured for a young individual buried in a house urn, typically interpreted as evidence for long distance contacts. The results are somewhat unexpected and provides new aspects into the complexity of Scandinavian Bronze Age societies.

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