Local dopamine production in the dorsal striatum restores goal-directed behavior in dopamine-deficient mice.

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.

Download Full-text

Viral restoration of dopamine signaling to the dorsal striatum restores instrumental conditioning to dopamine-deficient mice

Psychopharmacology ◽

10.1007/s00213-006-0579-9 ◽

2006 ◽

Vol 191 (3) ◽

pp. 567-578 ◽

Cited By ~ 48

Author(s):

Siobhan Robinson ◽

Aundrea J. Rainwater ◽

Thomas S. Hnasko ◽

Richard D. Palmiter

Keyword(s):

Instrumental Conditioning ◽

Dorsal Striatum ◽

Dopamine Signaling ◽

Deficient Mice

Download Full-text

Habitual versus Goal-directed Action Control in Parkinson Disease

Journal of Cognitive Neuroscience ◽

10.1162/jocn.2010.21514 ◽

2011 ◽

Vol 23 (5) ◽

pp. 1218-1229 ◽

Cited By ~ 67

Author(s):

Sanne de Wit ◽

Roger A. Barker ◽

Anthony D. Dickinson ◽

Roshan Cools

Keyword(s):

Parkinson Disease ◽

Disease Severity ◽

Habit Formation ◽

Dorsal Striatum ◽

Dopamine Depletion ◽

Conflict Task ◽

Stimulus Response ◽

Directed Action ◽

Goal Directed Behavior ◽

Direct Investigation

This study presents the first direct investigation of the hypothesis that dopamine depletion of the dorsal striatum in mild Parkinson disease leads to impaired stimulus–response habit formation, thereby rendering behavior slow and effortful. However, using an instrumental conflict task, we show that patients are able to rely on direct stimulus–response associations when a goal-directed strategy causes response conflict, suggesting that habit formation is not impaired. If anything our results suggest a disease severity–dependent deficit in goal-directed behavior. These results are discussed in the context of Parkinson disease and the neurobiology of habitual and goal-directed behavior.

Download Full-text

Dopamine receptor 1 neurons in the dorsal striatum regulate food anticipatory circadian activity rhythms in mice

eLife ◽

10.7554/elife.03781 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 58

Author(s):

Christian M Gallardo ◽

Martin Darvas ◽

Mia Oviatt ◽

Chris H Chang ◽

Mateusz Michalik ◽

...

Keyword(s):

Dopamine D2 Receptor ◽

D2 Receptor ◽

Dorsal Striatum ◽

D1 Receptor ◽

Circadian Oscillators ◽

Food Anticipatory Activity ◽

Dopamine Signaling ◽

Anticipatory Activity ◽

Dopamine Receptor 1 ◽

Deficient Mice

Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive. In this study, we show that mice lacking the dopamine D1 receptor (D1R KO mice) manifest greatly reduced FAA, whereas mice lacking the dopamine D2 receptor have normal FAA. To determine where dopamine exerts its effect, we limited expression of dopamine signaling to the dorsal striatum of dopamine-deficient mice; these mice developed FAA. Within the dorsal striatum, the daily rhythm of clock gene period2 expression was markedly suppressed in D1R KO mice. Pharmacological activation of D1R at the same time daily was sufficient to establish anticipatory activity in wild-type mice. These results demonstrate that dopamine signaling to D1R-expressing neurons in the dorsal striatum plays an important role in manifestation of FAA, possibly by synchronizing circadian oscillators that modulate motivational processes and behavioral output.

Download Full-text

Hippocampus and subregions of the dorsal striatum respond differently to a behavioral strategy change on a spatial navigation task

Journal of Neurophysiology ◽

10.1152/jn.00189.2015 ◽

2015 ◽

Vol 114 (3) ◽

pp. 1399-1416 ◽

Cited By ~ 25

Author(s):

Paul S. Regier ◽

Seiichiro Amemiya ◽

A. David Redish

Keyword(s):

Dorsal Striatum ◽

Relevant Information ◽

Behavioral Strategy ◽

Spatial Choice ◽

Ca1 Region ◽

Repetitive Tasks ◽

Reward Delivery ◽

Initial Learning ◽

Strategy Change ◽

Goal Directed Behavior

Goal-directed and habit-based behaviors are driven by multiple but dissociable decision making systems involving several different brain areas, including the hippocampus and dorsal striatum. On repetitive tasks, behavior transitions from goal directed to habit based with experience. Hippocampus has been implicated in initial learning and dorsal striatum in automating behavior, but recent studies suggest that subregions within the dorsal striatum have distinct roles in mediating habit-based and goal-directed behavior. We compared neural activity in the CA1 region of hippocampus with anterior dorsolateral and posterior dorsomedial striatum in rats on a spatial choice task, in which subjects experienced reward delivery changes that forced them to adjust their behavioral strategy. Our results confirm the importance of the hippocampus in evaluating predictive steps during goal-directed behavior, while separate circuits in the basal ganglia integrated relevant information during automation of actions and recognized when new behaviors were needed to continue obtaining rewards.

Download Full-text

Dopamine D2Receptor-Deficient Mice Exhibit Decreased Dopamine Transporter Function but No Changes in Dopamine Release in Dorsal Striatum

Journal of Neurochemistry ◽

10.1046/j.1471-4159.1999.0720148.x ◽

1999 ◽

Vol 72 (1) ◽

pp. 148-156 ◽

Cited By ~ 152

Author(s):

Shelly D. Dickinson ◽

Jilla Sabeti ◽

Gaynor A. Larson ◽

Karen Giardina ◽

Marcelo Rubinstein ◽

...

Keyword(s):

Dopamine Transporter ◽

Dopamine Release ◽

Dorsal Striatum ◽

Deficient Mice

Download Full-text

Unveiling the neural correlates of habit in the dorsal striatum

10.1101/2021.04.03.438314 ◽

2021 ◽

Author(s):

Youna Vandaele ◽

Patricia H Janak

Keyword(s):

Lever Press ◽

Dorsal Striatum ◽

Neural Correlates ◽

Discrete Trials ◽

Habitual Behavior ◽

Improved Performance ◽

Reward Availability ◽

Goal Directed Behavior ◽

Sustained Inhibition ◽

Spiking Activity

We have recently reported sustained inhibition in the dorsomedial striatum (DMS) and sustained excitation in the dorsolateral striatum (DLS) during execution of a lever press sequence in a discrete-trials task promoting habit. This sustained dorsostriatal activity was present early on, and did not clearly change in step with improved performance over ten training sessions. Early onset of sequence-related neural activity could have resulted from rapid habitual learning promoted by presentation of lever cues, predicting reward availability and delivery. To test this hypothesis, we compared DLS and DMS spiking activity in the discrete trials habit-promoting task with two task variants that promote goal-directed behavior. Comparison of the three tasks revealed that mean neuronal spiking activity was generally sustained across the lever press sequence in the task promoting habit and characterized by overall excitation in DLS and inhibition in DMS relative to baseline. In contrast, mean activity differences in DLS and DMS were much less prominent, and most changes occurred transiently around individual lever presses, in the tasks promoting goal-directed behavior. These results indicate that sequence delineation cues, such as the lever cues in these studies, promote habitual behavior and that this habitual behavior is encoded in the striatum by cue-triggered sustained DLS excitation and DMS inhibition that likely reflects cue-elicited behavioral chunking.

Download Full-text

Restoration of Dopamine Signaling to the Dorsal Striatum Is Sufficient for Aspects of Active Maternal Behavior in Female Mice

Endocrinology ◽

10.1210/en.2013-1257 ◽

2013 ◽

Vol 154 (11) ◽

pp. 4316-4327 ◽

Cited By ~ 26

Author(s):

Charles W. Henschen ◽

Richard D. Palmiter ◽

Martin Darvas

Keyword(s):

Nucleus Accumbens ◽

Maternal Behavior ◽

Dorsal Striatum ◽

Separate Group ◽

Grooming Behavior ◽

Female Mice ◽

Pup Retrieval ◽

Dopamine Signaling ◽

Motivated Behaviors ◽

Goal Directed Behavior

Striatal dopamine (DA) is important for motivated behaviors, including maternal behavior. Recent evidence linking the dorsal striatum with goal-directed behavior suggests that DA signaling in the dorsal striatum, not just the nucleus accumbens, could be involved in maternal behavior. To investigate this question, we tested the maternal behavior of mice with DA genetically restricted to the dorsal striatum. These mice had a mild deficit in pup retrieval but had normal licking/grooming and nursing behavior; consequently, pups were weaned successfully. We also tested a separate group of mice with severely depleted DA in all striatal areas. They had severe deficits in pup retrieval and licking/grooming behavior, whereas nursing behavior was left intact; again, pups survived to weaning at normal rates. We conclude that DA signaling in the striatum is a part of the circuitry mediating maternal behavior and is specifically relevant for active, but not passive, maternal behaviors. In addition, DA in the dorsal striatum is sufficient to allow for active maternal behavior.

Download Full-text

The SC-SNc pathway boosts appetitive locomotion in predatory hunting

10.1101/2020.11.23.395004 ◽

2020 ◽

Author(s):

Meizhu Huang ◽

Dapeng Li ◽

Qing Pei ◽

Zhiyong Xie ◽

Huating Gu ◽

...

Keyword(s):

Substantia Nigra ◽

Superior Colliculus ◽

Dopamine Release ◽

Dorsal Striatum ◽

Dopamine Neurons ◽

Substantia Nigra Pars Compacta ◽

Locomotion Speed ◽

Brain Circuit ◽

Goal Directed Behavior ◽

The Brain

ABSTRACTAppetitive locomotion is essential for organisms to approach rewards, such as food and prey. How the brain controls appetitive locomotion is poorly understood. In a naturalistic goal-directed behavior—predatory hunting, we demonstrate an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to boost appetitive locomotion. The SC-SNc pathway transmitted locomotion-speed signals to dopamine neurons and triggered dopamine release in the dorsal striatum. Activation of this pathway increased the speed and frequency of approach during predatory hunting, an effect that depended on the activities of SNc dopamine neurons. Conversely, synaptic inactivation of this pathway impaired appetitive locomotion but not defensive or exploratory locomotion. Together, these data revealed the SC as an important source to provide locomotion-related signals to SNc dopamine neurons to boost appetitive locomotion.

Download Full-text

Comparison of localization of metallothionein in tissues of metallothionein-deficient mice

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141585 ◽

1995 ◽

Vol 53 ◽

pp. 1042-1043

Author(s):

H. Nishimura ◽

R Nishimura ◽

D.L. Adelson ◽

A.E. Michaelska ◽

K.H.A. Choo ◽

...

Keyword(s):

Metal Binding ◽

Immunohistochemical Staining ◽

Squamous Epithelium ◽

Rabbit Antiserum ◽

Slight Modification ◽

Positive Control ◽

Heavy Metal Binding ◽

Critical Organ ◽

Metal Binding Protein ◽

Deficient Mice

Metallothionein (MT), a cysteine-rich heavy metal binding protein, has several isoforms designated from I to IV. Its major isoforms, I and II, can be induced by heavy metals like cadmium (Cd) and, are present in various organs of man and animals. Rodent testes are a critical organ to Cd and it is still a controversial matter whether MT exists in the testis although it is clear that MT is not induced by Cd in this tissue. MT-IV mRNA was found to localize within tongue squamous epithelium. Whether MT-III is present mainly glial cells or neurons has become a debatable topic. In the present study, we have utilized MT-I and II gene targeted mice and compared MT localization in various tissues from both MT-deficient mice and C57Black/6J mice (C57BL) which were used as an MT-positive control. For MT immunostaining, we have used rabbit antiserum against rat MT-I known to cross-react with mammalian MT-I and II and human MT-III. Immunohistochemical staining was conducted by the method described in the previous paper with a slight modification after the tissues were fixed in HistoChoice and embedded in paraffin.

Download Full-text