In Vivo and in Vitro Intracellular Recordings from Rat Midbrain Dopamine Neurons

1988 ◽  
Vol 537 (1 The Mesocorti) ◽  
pp. 51-76 ◽  
Author(s):  
ANTHONY A. GRACE
Keyword(s):  
Dopamine Neurons ◽  
Intracellular Recordings ◽  
Midbrain Dopamine ◽  
Midbrain Dopamine Neurons

scholarly journals Neuroprotective Potential of a Small Molecule RET Agonist in Cultured Dopamine Neurons and Hemiparkinsonian Rats

2021 ◽  
pp. 1-24
Author(s):  
Juho-Matti Renko ◽  
Arun Kumar Mahato ◽  
Tanel Visnapuu ◽  
Konsta Valkonen ◽  
Mati Karelson ◽  
...  
Keyword(s):  
Mapk Signaling ◽  
Dopamine Neurons ◽  
Dopamine Depletion ◽  
Wild Type ◽  
Disease Modifying Therapy ◽  
Immortalized Cells ◽  
Midbrain Dopamine ◽  
6 Hydroxydopamine

Background: Parkinson’s disease (PD) is a progressive neurological disorder where loss of dopamine neurons in the substantia nigra and dopamine depletion in the striatum cause characteristic motor symptoms. Currently, no treatment is able to halt the progression of PD. Glial cell line-derived neurotrophic factor (GDNF) rescues degenerating dopamine neurons both in vitro and in animal models of PD. When tested in PD patients, however, the outcomes from intracranial GDNF infusion paradigms have been inconclusive, mainly due to poor pharmacokinetic properties. Objective: We have developed drug-like small molecules, named BT compounds that activate signaling through GDNF’s receptor, the transmembrane receptor tyrosine kinase RET, both in vitro and in vivo and are able to penetrate through the blood-brain barrier. Here we evaluated the properties of BT44, a second generation RET agonist, in immortalized cells, dopamine neurons and rat 6-hydroxydopamine model of PD. Methods: We used biochemical, immunohistochemical and behavioral methods to evaluate the effects of BT44 on dopamine system in vitro and in vivo. Results: BT44 selectively activated RET and intracellular pro-survival AKT and MAPK signaling pathways in immortalized cells. In primary midbrain dopamine neurons cultured in serum-deprived conditions, BT44 promoted the survival of the neurons derived from wild-type, but not from RET knockout mice. BT44 also protected cultured wild-type dopamine neurons from MPP +-induced toxicity. In a rat 6-hydroxydopamine model of PD, BT44 reduced motor imbalance and could have protected dopaminergic fibers in the striatum. Conclusion: BT44 holds potential for further development into a novel, possibly disease-modifying therapy for PD.

scholarly journals In vivo functional diversity of midbrain dopamine neurons within identified axonal projections

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Navid Farassat ◽  
Kauê Machado Costa ◽  
Strahinja Stojanovic ◽  
Stefan Albert ◽  
Lora Kovacheva ◽  
...  
Keyword(s):  
Functional Diversity ◽  
Multiple Scales ◽  
Dopamine Neurons ◽  
Unit Recording ◽  
Axonal Projections ◽  
Intact Brain ◽  
Functional Topography ◽  
Midbrain Dopamine

Functional diversity of midbrain dopamine (DA) neurons ranges across multiple scales, from differences in intrinsic properties and connectivity to selective task engagement in behaving animals. Distinct in vitro biophysical features of DA neurons have been associated with different axonal projection targets. However, it is unknown how this translates to different firing patterns of projection-defined DA subpopulations in the intact brain. We combined retrograde tracing with single-unit recording and labelling in mouse brain to create an in vivo functional topography of the midbrain DA system. We identified differences in burst firing among DA neurons projecting to dorsolateral striatum. Bursting also differentiated DA neurons in the medial substantia nigra (SN) projecting either to dorsal or ventral striatum. We found differences in mean firing rates and pause durations among ventral tegmental area (VTA) DA neurons projecting to lateral or medial shell of nucleus accumbens. Our data establishes a high-resolution functional in vivo landscape of midbrain DA neurons.

Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo

Nature ◽  
2007 ◽  
Vol 448 (7149) ◽  
pp. 73-77 ◽  
Author(s):  
Päivi Lindholm ◽  
Merja H. Voutilainen ◽  
Juha Laurén ◽  
Johan Peränen ◽  
Veli-Matti Leppänen ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Dopamine Neurons ◽  
Midbrain Dopamine ◽  
Midbrain Dopamine Neurons

scholarly journals In Vivo Activation of Midbrain Dopamine Neurons via Sensitized, High-Affinity α6∗ Nicotinic Acetylcholine Receptors

Neuron ◽  
2008 ◽  
Vol 60 (1) ◽  
pp. 123-136 ◽  
Author(s):  
Ryan M. Drenan ◽  
Sharon R. Grady ◽  
Paul Whiteaker ◽  
Tristan McClure-Begley ◽  
Sheri McKinney ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Dopamine Neurons ◽  
Nicotinic Acetylcholine ◽  
High Affinity ◽  
Midbrain Dopamine ◽  
Midbrain Dopamine Neurons
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