scholarly journals Up-And-Down γ-Synuclein Transcription in Dopamine Neurons Translates Into Changes in Dopamine Neurotransmission and Behavioral Performance in Mice

2022 ◽  
Author(s):  
Rubén Pavia-Collado ◽  
Raquel Rodríguez-Aller ◽  
Diana Alarcón-Arís ◽  
Lluís Miquel-Rio ◽  
Esther Ruiz-Bronchal ◽  
...  
Keyword(s):  
Antisense Oligonucleotide ◽  
Water Maze ◽  
Viral Vector ◽  
Dopamine Neurons ◽  
Motor Deficits ◽  
Novel Object Recognition ◽  
Behavioral Performance ◽  
Limited Information ◽  
Midbrain Dopamine

The synuclein family consists of α-, β-, and γ-Synuclein (α-Syn, β-Syn, and γ-Syn), expressed in the neurons and concentrated in synaptic terminals. While α-Syn is at the center of interest due to its implication in the pathogenesis of Parkinson’s disease (PD) and other synucleinopathies, limited information exists on the other members. The current study aimed at investigating the biological role of γ-Syn controlling the midbrain dopamine (DA) function. We generated two different mouse models with i) γ-Syn overexpression induced by an adeno-associated viral vector and ii) γ-Syn knockdown induced by a ligand-conjugated antisense oligonucleotide, to modify the endogenous γ-Syn transcription levels in midbrain DA neurons. The progressive overexpression of γ-Syn decreased DA neurotransmission in the nigrostriatal and mesocortical pathways. In parallel, mice evoked motor deficits in the rotarod and impaired cognitive performance as assessed by novel object recognition, passive avoidance, and Morris water maze tests. Conversely, acute γ-Syn knockdown selectively in DA neurons facilitated forebrain DA neurotransmission. Importantly, modifications in γ-Syn expression did not induce the loss of DA neurons or changes in α-Syn expression. Collectively, our data strongly suggest that DA re-lease/re-uptake processes in the nigrostriatal and mesocortical pathways are partially dependent on SNc/VTA γ-Syn transcription levels, and are linked to modulation of DA transporter function, similar to α-Syn.

The Role of Vitamin D3 in the Development and Neuroprotection of Midbrain Dopamine Neurons

2016 ◽  
pp. 273-297 ◽  
Author(s):  
Rowan P. Orme ◽  
Charlotte Middleditch ◽  
Lauren Waite ◽  
Rosemary A. Fricker
Keyword(s):  
Vitamin D3 ◽  
Dopamine Neurons ◽  
Midbrain Dopamine ◽  
Midbrain Dopamine Neurons

scholarly journals A role of midbrain dopamine neurons in negative punishment

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S193
Author(s):  
Constance Peng ◽  
Philip Jean-Richard Dit Bressel ◽  
Gavan Mcnally
Keyword(s):  
Dopamine Neurons ◽  
Midbrain Dopamine ◽  
Midbrain Dopamine Neurons

scholarly journals Instantiation of incentive value and movement invigoration by distinct midbrain dopamine circuits

2017 ◽  
Author(s):  
Benjamin T. Saunders ◽  
Jocelyn M. Richard ◽  
Elyssa B. Margolis ◽  
Patricia H. Janak
Keyword(s):  
Dopamine Neuron ◽  
Dopamine Neurons ◽  
Neuron Activity ◽  
Temporal Association ◽  
Conditioned Stimuli ◽  
Incentive Value ◽  
Pavlovian Learning ◽  
Midbrain Dopamine ◽  
Dopamine Circuits

Environmental cues, through Pavlovian learning, become conditioned stimuli that guide animals towards the acquisition of “rewards” (i.e., food) that are necessary for survival. Here, we test the fundamental role of midbrain dopamine neurons in conferring predictive or motivational properties to cues, independent of external rewards. We demonstrate that phasic optogenetic excitation of dopamine neurons throughout the midbrain, when presented in temporal association with discrete sensory cues, is sufficient to instantiate those cues as conditioned stimuli that subsequently both evoke dopamine neuron activity on their own, and elicit cue-locked conditioned behaviors. Critically, we identify highly parcellated behavioral functions for dopamine neuron subpopulations projecting to discrete regions of striatum, revealing dissociable mesostriatal systems for the generation of incentive value and movement invigoration. These results show that dopamine neurons orchestrate Pavlovian conditioning via functionally heterogeneous, circuit-specific motivational signals to shape cue-controlled behavior.

scholarly journals Dopamine neuron-derived IGF-1 controls dopamine neuron firing, skill learning, and exploration

2019 ◽  
Vol 116 (9) ◽  
pp. 3817-3826 ◽  
Author(s):  
Alessandro Pristerà ◽  
Craig Blomeley ◽  
Emanuel Lopes ◽  
Sarah Threlfell ◽  
Elisa Merlini ◽  
...  
Keyword(s):  
Cognitive Processes ◽  
Skill Learning ◽  
Dopamine Neuron ◽  
Dopamine Neurons ◽  
Neuron Firing ◽  
Adult Mice ◽  
Conditional Deletion ◽  
Dopamine Content ◽  
Midbrain Dopamine

Midbrain dopamine neurons, which can be regulated by neuropeptides and hormones, play a fundamental role in controlling cognitive processes, reward mechanisms, and motor functions. The hormonal actions of insulin-like growth factor 1 (IGF-1) produced by the liver have been well described, but the role of neuronally derived IGF-1 remains largely unexplored. We discovered that dopamine neurons secrete IGF-1 from the cell bodies following depolarization, and that IGF-1 controls release of dopamine in the ventral midbrain. In addition, conditional deletion of dopamine neuron-derived IGF-1 in adult mice leads to decrease of dopamine content in the striatum and deficits in dopamine neuron firing and causes reduced spontaneous locomotion and impairments in explorative and learning behaviors. These data identify that dopamine neuron-derived IGF-1 acts as a regulator of dopamine neurons and regulates dopamine-mediated behaviors.

Evidence for a modulatory role of Ih on the firing of a subgroup of midbrain dopamine neurons

Neuroreport ◽  
2001 ◽  
Vol 12 (2) ◽  
pp. 255-258 ◽  
Author(s):  
Vincent Seutin ◽  
Laurent Massotte ◽  
Michel-François Renette ◽  
Albert Dresse
Keyword(s):  
Dopamine Neurons ◽  
Midbrain Dopamine ◽  
Midbrain Dopamine Neurons

scholarly journals Basal forebrain mediates prosocial behavior via disinhibition of midbrain dopamine neurons

2021 ◽  
Vol 118 (7) ◽  
pp. e2019295118
Author(s):  
Jun Wang ◽  
Jie Li ◽  
Qian Yang ◽  
Ya-Kai Xie ◽  
Ya-Lan Wen ◽  
...  
Keyword(s):  
Social Interaction ◽  
Prosocial Behavior ◽  
Basal Forebrain ◽  
Social Preference ◽  
Dopamine Neurons ◽  
Inhibitory Neurons ◽  
Axon Terminals ◽  
Midbrain Dopamine ◽  
Da Release

Sociability is fundamental for our daily life and is compromised in major neuropsychiatric disorders. However, the neuronal circuit mechanisms underlying prosocial behavior are still elusive. Here we identify a causal role of the basal forebrain (BF) in the control of prosocial behavior via inhibitory projections that disinhibit the midbrain ventral tegmental area (VTA) dopamine (DA) neurons. Specifically, BF somatostatin-positive (SST) inhibitory neurons were robustly activated during social interaction. Optogenetic inhibition of these neurons in BF or their axon terminals in the VTA largely abolished social preference. Electrophysiological examinations further revealed that SST neurons predominantly targeted VTA GABA neurons rather than DA neurons. Consistently, optical inhibition of SST neuron axon terminals in the VTA decreased DA release in the nucleus accumbens during social interaction, confirming a disinhibitory action. These data reveal a previously unappreciated function of the BF in prosocial behavior through a disinhibitory circuitry connected to the brain’s reward system.

scholarly journals Hyperpolarization-Activated Cation Current (Ih) Is an Ethanol Target in Midbrain Dopamine Neurons of Mice

2006 ◽  
Vol 95 (2) ◽  
pp. 619-626 ◽  
Author(s):  
Takashi Okamoto ◽  
Mark T. Harnett ◽  
Hitoshi Morikawa
Keyword(s):  
Firing Frequency ◽  
Dopamine Neurons ◽  
Pacemaker Activity ◽  
Activation Kinetics ◽  
Dopaminergic Transmission ◽  
Cation Current ◽  
Midbrain Dopamine ◽  
Maximum Conductance

Ethanol stimulates the firing activity of midbrain dopamine (DA) neurons, leading to enhanced dopaminergic transmission in the mesolimbic system. This effect is thought to underlie the behavioral reinforcement of alcohol intake. Ethanol has been shown to directly enhance the intrinsic pacemaker activity of DA neurons, yet the cellular mechanism mediating this excitation remains poorly understood. The hyperpolarization-activated cation current, Ih, is known to contribute to the pacemaker firing of DA neurons. To determine the role of Ih in ethanol excitation of DA neurons, we performed patch-clamp recordings in acutely prepared mouse midbrain slices. Superfusion of ethanol increased the spontaneous firing frequency of DA neurons in a reversible fashion. Treatment with ZD7288, a blocker of Ih, irreversibly depressed basal firing frequency and significantly attenuated the stimulatory effect of ethanol on firing. Furthermore, ethanol reversibly augmented Ih amplitude and accelerated its activation kinetics. This effect of ethanol was accompanied by a shift in the voltage dependence of Ih activation to more depolarized potentials and an increase in the maximum Ih conductance. Cyclic AMP mediated the depolarizing shift in Ih activation but not the increase in the maximum conductance. Finally, repeated ethanol treatment in vivo induced downregulation of Ih density in DA neurons and an accompanying reduction in the magnitude of ethanol stimulation of firing. These results suggest an important role of Ih in the reinforcing actions of ethanol and in the neuroadaptations underlying escalation of alcohol consumption associated with alcoholism.

The potential role of cholecystokinin in schizophrenia: review and update

1993 ◽  
Vol 8 (2) ◽  
pp. 67-78 ◽  
Author(s):  
R Payeur ◽  
MK Nixon ◽  
M Bourin ◽  
J Bradwejn ◽  
JM Legrand
Keyword(s):  
Clinical Trials ◽  
Potential Role ◽  
Dopamine Neurons ◽  
Receptor Subtype ◽  
Potential Treatment ◽  
Specific Receptor ◽  
Cholecystokinin Antagonists ◽  
Midbrain Dopamine ◽  
Midbrain Dopamine Neurons

SummaryThe role of the neuropeptide cholecystokinin in schizophrenia has been widely explored because of its modulating action on midbrain dopamine neurons. The recent discovery of more specific receptor subtype cholecystokinin antagonists should be considered as potential treatment for schizophrenia with fewer side effects. This paper reviews cholecystokinin/dopamine interactions in animal and human studies. Clinical trials with cholecystokinin agonists and antagonists in schizophrenia are updated.

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