Dopamine D3 and acetylcholine nicotinic receptor heteromerization in midbrain dopamine neurons: Relevance for neuroplasticity

What does this mean for our needed neuroplasticity? Should we be taking nicotine? Via smoking? Patches? Gum? eCigarettes? Whom the hell is going to answer that simple question? Our fucking failures of stroke associations can once again prove their fucking failures by not even knowing that answering this question could help survivors recover.
http://www.sciencedirect.com/science/article/pii/S0924977X17300482

• Leonardo Bontempi^, ,
• Paola Savoia,
• Federica Bono,
• Chiara Fiorentini,
• Cristina Missale

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http://dx.doi.org/10.1016/j.euroneuro.2017.01.015

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Abstract

Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer² (BRET²) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET² showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET² signal generated by D3R-GFP² and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine.

Keywords

• Nicotine;
• Heteromerization;
• Plasticity;
• Dopamine;
• D3 Receptor;
• Nicotinic receptor

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Corresponding author.

© 2017 Elsevier B.V. and ECNP. All rights reserved.

Mechanisms of Nicotinic Modulation of Glutamatergic Neuroplasticity in Humans

What does this mean for our needed neuroplasticity? Should we be taking nicotine? Via smoking? Patches? Gum? eCigarettes? Whom the hell is going to answer that simple question? Our fucking failures of stroke associations can once again prove their fucking failures by not even knowing that answering this question could help survivors recover.
http://cercor.oxfordjournals.org/content/early/2015/10/21/cercor.bhv252.abstract

1. Marcelo Di Marcello Valladão Lugon1,2,
2. Giorgi Batsikadze2,
3. Shane Fresnoza2,
4. Jessica Grundey2,
5. Min-Fang Kuo2,
6. Walter Paulus2,
7. Ester Miyuki Nakamura-Palacios1,† and
8. Michael A. Nitsche2,3,4,†

+ Author Affiliations

1. ¹Laboratory of Cognitive Sciences and Neuropsychopharmacology, Program of Post-Graduation in Physiological Sciences, Federal University of Espírito Santo, Vitória-ES, Brazil
2. ²Department of Clinical Neurophysiology, University Medical Center, Georg-August-University, Göttingen 37075, Germany
3. ³Leibniz Research Centre for Working Environment and Human Resources, Dortmund, Germany
4. ⁴Department of Neurology, University Medical Hospital Bergmannsheil, Bochum, Germany

1. Address correspondence to Dr Michael A. Nitsche, Leibniz Research Centre for Working Environment and Human Resources, Ardeystr. 67, 44139 Dortmund, Germany. Email: nitsche@ifado.de

1. ↵† Ester Miyuki Nakamura-Palacios and Michael A. Nitsche contributed equally to this study.

Abstract

The impact of nicotine (NIC) on plasticity is thought to be primarily determined via calcium channel properties of nicotinic receptor subtypes, and glutamatergic plasticity is likewise calcium-dependent. Therefore glutamatergic plasticity is likely modulated by the impact of nicotinic receptor-dependent neuronal calcium influx. We tested this hypothesis for transcranial direct current stimulation (tDCS)-induced long-term potentiation-like plasticity, which is abolished by NIC in nonsmokers. To reduce calcium influx under NIC, we blocked N-methyl-d-aspartate (NMDA) receptors. We applied anodal tDCS combined with 15 mg NIC patches and the NMDA-receptor antagonist dextromethorphan (DMO) in 3 different doses (50, 100, and 150 mg) or placebo medication. Corticospinal excitability was monitored by single-pulse transcranial magnetic stimulation-induced motor-evoked potential amplitudes after plasticity induction. NIC abolished anodal tDCS-induced motor cortex excitability enhancement, which was restituted under medium dosage of DMO. Low-dosage DMO did not affect the impact of NIC on tDCS-induced plasticity and high-dosage DMO abolished plasticity. For DMO alone, the low dosage had no effect, but medium and high dosages abolished tDCS-induced plasticity. These results enhance our knowledge about the proposed calcium-dependent impact of NIC on plasticity in humans and might be relevant for the development of novel nicotinic treatments for cognitive dysfunction.

Yale team finds nicotinic receptor essential for cognition — and mental health

Another reason to have a patch or eCig after your stroke. At least in my opinion and my opinion is worthless, no medical background.
I'm reading this in a paper on schizophrenia, I'm sure your stroke doctor has this on his/her reading list. 

Yale team finds nicotinic receptor essential for cognition — and mental health

One paragraph from there;
Acetycholine is released when we are awake — but not in deep sleep. These receptors allow prefrontal circuits to come “online” when we awaken, allowing us to perform complex mental tasks. This process is enhanced by caffeine in coffee, which increases acetylcholine release. As their name suggests, nicotinic alpha-7 receptors are also activated by nicotine, which may may help to explain why smoking can focus attention and calm behavior, functions of the prefrontal cortex.
Look at that Amy - Coffee