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.

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.

Modulation of Somatodendritic Dopamine Release by Endogenous H2O2: Susceptibility in Substantia Nigra But Resistance in VTA

2002 ◽  
Vol 87 (2) ◽  
pp. 1155-1158 ◽  
Author(s):  
Billy T. Chen ◽  
Marat V. Avshalumov ◽  
Margaret E. Rice
Keyword(s):  
Nucleus Accumbens ◽  
Substantia Nigra ◽  
Dopamine Release ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
Substantia Nigra Pars Compacta ◽  
Fast Scan Cyclic Voltammetry ◽  
Carbon Fiber Microelectrodes ◽  
Da Release ◽  
Striking Contrast

We showed previously that dopamine (DA) release in dorsal striatum is inhibited by endogenously generated hydrogen peroxide (H2O2). Here, we examined whether endogenous H2O2 can also modulate somatodendritic DA release in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), with companion measurements in DA terminal regions. Evoked DA release was monitored in brain slices using carbon-fiber microelectrodes with fast-scan cyclic voltammetry. Exogenous H2O2decreased DA release by 50–60% in SNc and VTA but only by 35% in nucleus accumbens. Whether endogenous H2O2 also modulated somatodendritic release was examined using the glutathione peroxidase inhibitor, mercaptosuccinate (MCS), which should increase stimulation-evoked H2O2levels. In the presence of MCS, DA release was suppressed by 30–40% in SNc as well as in dorsal striatum and nucleus accumbens. In striking contrast, DA release in the VTA was unaffected by MCS. These data are consistent with stronger H2O2 regulation or lower H2O2 generation in VTA than in the other regions. Importantly, oxidative stress has been linked causally to Parkinson's disease, in which DA cells in SNc degenerate, but VTA cells are spared. The present data suggest that differences in oxidant regulation or generation between SNc and VTA could contribute to this.

scholarly journals The tectonigral pathway regulates appetitive locomotion in predatory hunting in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Meizhu Huang ◽  
Dapeng Li ◽  
Xinyu Cheng ◽  
Qing Pei ◽  
Zhiyong Xie ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Superior Colliculus ◽  
Dopamine Release ◽  
Dorsal Striatum ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Neuronal Circuitry ◽  
Locomotion Speed ◽  
Brain Circuit ◽  
Goal Directed Behavior

AbstractAppetitive locomotion is essential for animals to approach rewards, such as food and prey. The neuronal circuitry controlling appetitive locomotion is unclear. In a goal-directed behavior—predatory hunting, we show an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to enhance appetitive locomotion in mice. This tectonigral pathway transmits locomotion-speed signals to dopamine neurons and triggers dopamine release in the dorsal striatum. Synaptic inactivation of this pathway impairs appetitive locomotion but not defensive locomotion. Conversely, activation of this pathway increases the speed and frequency of approach during predatory hunting, an effect that depends on the activities of SNc dopamine neurons. Together, these data reveal that the SC regulates locomotion-speed signals to SNc dopamine neurons to enhance appetitive locomotion in mice.

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 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.

scholarly journals Plasticity in striatal dopamine release is governed by release-independent depression and the dopamine transporter

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Mark D. Condon ◽  
Nicola J. Platt ◽  
Yan-Feng Zhang ◽  
Bradley M. Roberts ◽  
Michael A. Clements ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
Dopaminergic Neurons ◽  
Action Potentials ◽  
Dopamine Release ◽  
Ex Vivo ◽  
Dorsal Striatum ◽  
Short Term ◽  
Fast Scan Cyclic Voltammetry ◽  
Short Term Plasticity ◽  
Initial Release

Abstract Mesostriatal dopaminergic neurons possess extensively branched axonal arbours. Whether action potentials are converted to dopamine output in the striatum will be influenced dynamically and critically by axonal properties and mechanisms that are poorly understood. Here, we address the roles for mechanisms governing release probability and axonal activity in determining short‐term plasticity of dopamine release, using fast‐scan cyclic voltammetry in the ex vivo mouse striatum. We show that brief short‐term facilitation and longer short term depression are only weakly dependent on the level of initial release, i.e. are release insensitive. Rather, short-term plasticity is strongly determined by mechanisms which govern axonal activation, including K+‐gated excitability and the dopamine transporter, particularly in the dorsal striatum. We identify the dopamine transporter as a master regulator of dopamine short‐term plasticity, governing the balance between release‐dependent and independent mechanisms that also show region‐specific gating.

scholarly journals Age-dependent effects of protein restriction on dopamine release

2020 ◽  
Vol 46 (2) ◽  
pp. 394-403
Author(s):  
Fabien Naneix ◽  
Kate Z. Peters ◽  
Andrew M. J. Young ◽  
James E. McCutcheon
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Release ◽  
Physiological State ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
Protein Restriction ◽  
Fast Scan Cyclic Voltammetry ◽  
Health And Development ◽  
Late Maturation ◽  
The Impact

AbstractDespite the essential role of protein intake for health and development, very little is known about the impact of protein restriction on neurobiological functions, especially at different stages of the lifespan. The dopamine system is a central actor in the integration of food-related processes and is influenced by physiological state and food-related signals. Moreover, it is highly sensitive to dietary effects during early life periods such as adolescence due to its late maturation. In the present study, we investigated the impact of protein restriction either during adolescence or adulthood on the function of the mesolimbic (nucleus accumbens) and nigrostriatal (dorsal striatum) dopamine pathways using fast-scan cyclic voltammetry in rat brain slices. In the nucleus accumbens, protein restriction in adults increased dopamine release in response to low and high frequency trains of stimulation (1–20 Hz). By contrast, protein restriction during adolescence decreased nucleus accumbens dopamine release. In the dorsal striatum, protein restriction at adulthood has no impact on dopamine release but the same diet during adolescence induced a frequency-dependent increase in stimulated dopamine release. Taken together, our results highlight the sensitivity of the different dopamine pathways to the effect of protein restriction, as well as their vulnerability to deleterious diet effects at different life stages.

scholarly journals Striatonigrostriatal Circuit Architecture for Disinhibition of Dopamine Signaling

2021 ◽  
Author(s):  
Priscilla Ambrosi ◽  
Talia N Lerner
Keyword(s):  
Basal Ganglia ◽  
Dopamine Release ◽  
Habit Formation ◽  
Open Loop ◽  
Closed Loops ◽  
Parallel Circuit ◽  
Parallel Loops ◽  
Dopamine Signaling ◽  
Goal Directed Behavior ◽  
Dorsomedial Striatum

The basal ganglia operate largely in closed parallel loops, including an associative circuit for goal-directed behavior originating from the dorsomedial striatum (DMS) and a somatosensory circuit important for habit formation originating from the dorsolateral striatum (DLS). An exception to this parallel circuit organization has been proposed to explain how information might be transferred between striatal subregions, for example from DMS to DLS during habit formation. The "ascending spiral hypothesis" proposes that DMS disinhibits dopamine signaling in DLS through a tri-synaptic, open-loop striato-nigro-striatal circuit. Here, we used transsynaptic and intersectional genetic tools to investigate both closed- and open-loop striato-nigro-striatal circuits. We found strong evidence for closed loops, which would allow striatal subregions to regulate their own dopamine release. We also found evidence for functional synapses in open loops. However, these synapses were unable to modulate tonic dopamine neuron firing, questioning the prominence of their role in mediating crosstalk between striatal subregions.

scholarly journals Plasticity in striatal dopamine release is governed by release-independent depression and the dopamine transporter

2018 ◽  
Author(s):  
Mark D. Condon ◽  
Nicola J. Platt ◽  
Yan-Feng Zhang ◽  
Bradley M. Roberts ◽  
Michael A. Clements ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
Dopamine Release ◽  
Ex Vivo ◽  
Dorsal Striatum ◽  
List Type ◽  
Short Term ◽  
Fast Scan Cyclic Voltammetry ◽  
Short Term Plasticity ◽  
Initial Release ◽  
Axonal Excitability

AbstractMesostriatal DA neurons possess extensively branched axonal arbours. Whether action potentials are converted to DA output in striatum will be influenced dynamically and critically by axonal properties and mechanisms that are poorly understood. We addressed the roles for mechanisms governing release probability and axonal activity in determining short-term plasticity of DA release, using fast-scan cyclic voltammetry in ex vivo mouse striatum. Brief short-term facilitation (STF) and longer short-term depression (STD) were only weakly dependent on the level of initial release, i.e. were release-insensitive. Rather, short-term plasticity was strongly determined by mechanisms which governed axonal activation, including K+-gated excitability and the dopamine transporter (DAT), particularly in dorsal striatum. We identify the DAT as a master regulator of DA short-term plasticity, governing the balance between release-dependent and independent mechanisms that also show region-specific gating.Key FindingsShort-term plasticity in dopamine release is only weakly governed by initial releaseShort-term depression is strongly dependent on axonal excitability and activationThe dopamine transporter controls short-term plasticity and drives short-term depressionDopamine transporters govern the balance between release-dependent and -independent mechanisms

scholarly journals Age dependent effects of protein restriction on dopamine release

2020 ◽  
Author(s):  
Fabien Naneix ◽  
Kate Z. Peters ◽  
Andrew M. J. Young ◽  
James E. McCutcheon
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Release ◽  
Physiological State ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
Protein Restriction ◽  
Fast Scan Cyclic Voltammetry ◽  
Health And Development ◽  
Late Maturation ◽  
The Impact

ABSTRACTDespite the essential role of protein intake for health and development, very little is known about the impact of protein restriction on neurobiological functions, especially at different stages of the lifespan. The dopamine system is a central actor in the integration of food-related processes and is influenced by physiological state and food-related signals. Moreover, it is highly sensitive to dietary effects during early life periods such as adolescence due to its late maturation. In the present study, we investigated the impact of protein restriction either during adolescence or adulthood on the function of the mesolimbic (nucleus accumbens) and nigrostriatal (dorsal striatum) dopamine pathways using fast-scan cyclic voltammetry in rat brain slices. In the nucleus accumbens, protein restriction in adults increased dopamine release in response to low and high frequency trains of stimulation (1-20 Hz). By contrast, protein restriction performed at adolescence decreased nucleus accumbens dopamine release. In the dorsal striatum, protein restriction has no impact on dopamine release when performed at adulthood but in adolescent rats we observed frequency-dependent increases in stimulated dopamine release. Taken together, our results highlight the sensitivity of the different dopamine pathways to the effect of protein restriction, as well as their vulnerability to deleterious diet effects at different life stages.

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