The effect of long-term diethylstilbestrol treatment or hyperprolactinemia on the response of the tuberoinfundibular dopamine neurons to elevated prolactin

Parkinson’s disease (PD) is one of the common long-term degenerative disorders that primarily affect motor systems. Gastrointestinal (GI) symptoms are common in individuals with PD and often present before motor symptoms. It has been found that gut dysbiosis to PD pathology is related to the severity of motor and non-motor symptoms in PD. Probiotics have been reported to have the ability to improve the symptoms related to constipation in PD patients. However, the evidence from preclinical or clinical research to verify the beneficial effects of probiotics for the motor functions in PD is still limited. An experimental PD animal model could be helpful in exploring the potential therapeutic strategy using probiotics. In the current study, we examined whether daily and long-term administration of probiotics has neuroprotective effects on nigrostriatal dopamine neurons and whether it can further alleviate the motor dysfunctions in PD mice. Transgenic MitoPark PD mice were chosen for this study and the effects of daily probiotic treatment on gait, beam balance, motor coordination, and the degeneration levels of dopaminergic neurons were identified. From the results, compared with the sham treatment group, we found that the daily administration of probiotics significantly reduced the motor impairments in gait pattern, balance function, and motor coordination. Immunohistochemically, a tyrosine hydroxylase (TH)-positive cell in the substantia nigra was significantly preserved in the probiotic-treated PD mice. These results showed that long-term administration of probiotics has neuroprotective effects on dopamine neurons and further attenuates the deterioration of motor dysfunctions in MitoPark PD mice. Our data further highlighted the promising possibility of the potential use of probiotics, which could be the relevant approach for further application on human PD subjects.

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A Possible Role of Midbrain Dopamine Neurons in Short- and Long-Term Adaptation of Saccades to Position-Reward Mapping

Journal of Neurophysiology ◽

10.1152/jn.00238.2004 ◽

2004 ◽

Vol 92 (4) ◽

pp. 2520-2529 ◽

Cited By ~ 47

Author(s):

Yoriko Takikawa ◽

Reiko Kawagoe ◽

Okihide Hikosaka

Keyword(s):

Visual Cues ◽

Early Stage ◽

Intermediate Stage ◽

Saccade Latency ◽

Dopamine Neurons ◽

Neuronal Responses ◽

Sensory Stimuli ◽

Reward Delivery ◽

Midbrain Dopamine

Dopamine (DA) neurons respond to sensory stimuli that predict reward. To understand how DA neurons acquire such ability, we trained monkeys on a one-direction-rewarded version of memory-guided saccade task (1DR) only when we recorded from single DA neurons. In 1DR, position-reward mapping was changed across blocks of trials. In the early stage of training of 1DR, DA neurons responded to reward delivery; in the later stages, they responded predominantly to the visual cue that predicted reward or no reward (reward predictor) differentially. We found that such a shift of activity from reward to reward predictor also occurred within a block of trials after position-reward mapping was altered. A main effect of long-term training was to accelerate the within-block reward-to-predictor shift of DA neuronal responses. The within-block shift appeared first in the intermediate stage, but was slow, and DA neurons often responded to the cue that indicated reward in the preceding block. In the advanced stage, the reward-to-predictor shift occurred quickly such that the DA neurons' responses to visual cues faithfully matched the current position-reward mapping. Changes in the DA neuronal responses co-varied with the reward-predictive differentiation of saccade latency both in short-term (within-block) and long-term adaptation. DA neurons' response to the fixation point also underwent long-term changes until it occurred predominantly in the first trial within a block. This might trigger a switch between the learned sets. These results suggest that midbrain DA neurons play an essential role in adapting oculomotor behavior to frequent switches in position-reward mapping.

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D2 Dopamine Receptor Activation Facilitates Endocannabinoid-Mediated Long-Term Synaptic Depression of GABAergic Synaptic Transmission in Midbrain Dopamine Neurons via cAMP-Protein Kinase A Signaling

Journal of Neuroscience ◽

10.1523/jneurosci.4035-08.2008 ◽

2008 ◽

Vol 28 (52) ◽

pp. 14018-14030 ◽

Cited By ~ 80

Author(s):

B. Pan ◽

C. J. Hillard ◽

Q.-s. Liu

Keyword(s):

Protein Kinase ◽

Protein Kinase A ◽

Receptor Activation ◽

Dopamine Neurons ◽

D2 Dopamine Receptor ◽

Midbrain Dopamine ◽

Gabaergic Synaptic Transmission ◽

Kinase A ◽

Midbrain Dopamine Neurons

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Differential expression of long-term potentiation among identified inhibitory inputs to dopamine neurons

Journal of Neurophysiology ◽

10.1152/jn.00270.2017 ◽

2017 ◽

Vol 118 (4) ◽

pp. 1998-2008 ◽

Cited By ~ 6

Author(s):

DeNard V. Simmons ◽

Alyssa K. Petko ◽

Carlos A. Paladini

Keyword(s):

Nucleus Accumbens ◽

Adenylyl Cyclase ◽

Ventral Tegmental Area ◽

Cyclic Gmp ◽

Long Term Potentiation ◽

Dopamine Neurons ◽

Gaba Neurons ◽

Tegmental Nucleus ◽

Term Potentiation

The in vivo firing pattern of ventral tegmental area (VTA) dopamine neurons is controlled by GABA afferents originating primarily from the nucleus accumbens (NAc), rostromedial tegmental nucleus (RMTg), and local GABA neurons within the VTA. Although different forms of plasticity have been observed from GABA inputs to VTA dopamine neurons, one dependent on cyclic GMP synthesis and the other on adenylyl cyclase activation, it is unknown whether plasticity is differentially expressed in each. Using an optogenetic strategy, we show that identified inhibitory postsynaptic currents (IPSCs) from local VTA GABA neurons and NAc afferents exhibit a cyclic GMP-dependent long-term potentiation (LTP) that is capable of inhibiting the firing activity of dopamine neurons. However, this form of LTP was not induced from RMTg afferents. Only an adenylyl cyclase-mediated increase in IPSCs was exhibited by all three inputs. Thus discrete plasticity mechanisms recruit overlapping but different subsets of GABA inputs to VTA dopamine neurons. NEW & NOTEWORTHY We describe a mapping of plasticity expression, mediated by different mechanisms, among three distinct GABA afferents to ventral tegmental area (VTA) dopamine neurons: the rostromedial tegmental nucleus, the nucleus accumbens, and the local GABA neurons within the VTA known to synapse on VTA dopamine neurons. This work is the first demonstration that discrete plasticity mechanisms recruit overlapping but different subsets of GABA inputs to VTA dopamine neurons.

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Brain Grafting as a Treatment for Parkinson's Disease

Neurosurgery ◽

10.1227/00006123-198702000-00026 ◽

1987 ◽

Vol 20 (2) ◽

pp. 335-342 ◽

Cited By ~ 21

Author(s):

Mark J. Perlow

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Manifestations ◽

Dopamine Neurons ◽

Clinical Aspects ◽

Pathological Changes ◽

Pharmacological Treatments ◽

The Central Nervous System ◽

The Brain

Abstract Parkinson's disease is an illness with neuropathological and neuroanatomical abnormalities in many areas of the central nervous system. Some clinical manifestations of this illness are correlated with pathological changes in the substantia nigra and with a loss of dopamine in the nigra and striatum. The most effective pharmacological treatments have used agents that either replace the lost dopamine or act as agonists on dopamine receptors. Recent studies in animal models of Parkinson's disease demonstrate that the loss of dopamine and many clinical manifestations of dopamine reduction can be reversed by transplantation of fetal dopamine-containing cells to specific dopamine-depleted areas of the brain. Long term viability of these transplants has also been demonstrated. The author suggests that the transplantation of dopamine neurons, even across species barriers, is a reasonable consideration for the treatment of human Parkinson's disease. This article reviews in detail the results of recent experiments and how the experience in these models might be utilized in determining a transplantation strategy for the treatment of specific clinical aspects of this illness.

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Dopamine, behavior, and addiction

Journal of Biomedical Science ◽

10.1186/s12929-021-00779-7 ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Roy A. Wise ◽

Chloe J. Jordan

Keyword(s):

Dopaminergic Neurons ◽

Long Term Potentiation ◽

Burst Firing ◽

Dopamine Neurons ◽

Dopamine System ◽

Learned Behavior ◽

Sensory Inputs ◽

Addictive Drugs ◽

Term Potentiation

AbstractAddictive drugs are habit-forming. Addiction is a learned behavior; repeated exposure to addictive drugs can stamp in learning. Dopamine-depleted or dopamine-deleted animals have only unlearned reflexes; they lack learned seeking and learned avoidance. Burst-firing of dopamine neurons enables learning—long-term potentiation (LTP)—of search and avoidance responses. It sets the stage for learning that occurs between glutamatergic sensory inputs and GABAergic motor-related outputs of the striatum; this learning establishes the ability to search and avoid. Independent of burst-firing, the rate of single-spiking—or “pacemaker firing”—of dopaminergic neurons mediates motivational arousal. Motivational arousal increases during need states and its level determines the responsiveness of the animal to established predictive stimuli. Addictive drugs, while usually not serving as an external stimulus, have varying abilities to activate the dopamine system; the comparative abilities of different addictive drugs to facilitate LTP is something that might be studied in the future.

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Firing patterns of serotonin neurons underlying cognitive flexibility

10.1101/059758 ◽

2016 ◽

Cited By ~ 3

Author(s):

Sara Matias ◽

Eran Lottem ◽

Guillaume P. Dugué ◽

Zachary F. Mainen

Keyword(s):

Cognitive Flexibility ◽

Causal Structure ◽

Dopamine Neurons ◽

Prediction Errors ◽

Firing Patterns ◽

Learning Rates ◽

Serotonin Neurons ◽

Endogenous Role ◽

Flexible Adaptation

Serotonin is implicated in mood and affective disorders1,2 but growing evidence suggests that its core endogenous role may be to promote flexible adaptation to changes in the causal structure of the environment3–8. This stems from two functions of endogenous serotonin activation: inhibiting learned responses that are not currently adaptive9,10 and driving plasticity to reconfigure them1113. These mirror dual functions of dopamine in invigorating reward-related responses and promoting plasticity that reinforces new ones16,17. However, while dopamine neurons are known to be activated by reward prediction errors18,19, consistent with theories of reinforcement learning, the reported firing patterns of serotonin neurons21–23 do not accord with any existing theories1,24,25. Here, we used long-term photometric recordings in mice to study a genetically-defined population of dorsal raphe serotonin neurons whose activity we could link to normal reversal learning. We found that these neurons are activated by both positive and negative prediction errors, thus reporting the kind of surprise signal proposed to promote learning in conditions of uncertainty26,27. Furthermore, by comparing cue responses of serotonin and dopamine neurons we found differences in learning rates that could explain the importance of serotonin in inhibiting perseverative responding. Together, these findings show how the firing patterns of serotonin neurons support a role in cognitive flexibility and suggest a revised model of dopamine-serotonin opponency with potential clinical implications.

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