scholarly journals Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons

Science ◽  
2015 ◽  
Vol 350 (6256) ◽  
pp. 102-106 ◽  
Author(s):  
Jae-Ick Kim ◽  
Subhashree Ganesan ◽  
Sarah X. Luo ◽  
Yu-Wei Wu ◽  
Esther Park ◽  
...  
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Dopaminergic Neurons ◽  
Dopamine Neurons ◽  
Inhibitory Neurotransmitter ◽  
Midbrain Dopaminergic Neurons ◽  
Evolutionarily Conserved ◽  
Gaba Synthesis ◽  
Midbrain Dopamine ◽  
Midbrain Dopamine Neurons

Midbrain dopamine neurons are an essential component of the basal ganglia circuitry, playing key roles in the control of fine movement and reward. Recently, it has been demonstrated that γ-aminobutyric acid (GABA), the chief inhibitory neurotransmitter, is co-released by dopamine neurons. Here, we show that GABA co-release in dopamine neurons does not use the conventional GABA-synthesizing enzymes, glutamate decarboxylases GAD65 and GAD67. Our experiments reveal an evolutionarily conserved GABA synthesis pathway mediated by aldehyde dehydrogenase 1a1 (ALDH1a1). Moreover, GABA co-release is modulated by ethanol (EtOH) at concentrations seen in blood alcohol after binge drinking, and diminished ALDH1a1 leads to enhanced alcohol consumption and preference. These findings provide insights into the functional role of GABA co-release in midbrain dopamine neurons, which may be essential for reward-based behavior and addiction.

Midbrain dopaminergic innervation of the hippocampus is sufficient to modulate formation of aversive memories

2021 ◽  
Vol 118 (40) ◽  
pp. e2111069118
Author(s):  
Theodoros Tsetsenis ◽  
Julia K. Badyna ◽  
Julianne A. Wilson ◽  
Xiaowen Zhang ◽  
Elizabeth N. Krizman ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Dorsal Hippocampus ◽  
Memory Formation ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Aversive Learning ◽  
Contextual Fear ◽  
Dopaminergic Transmission ◽  
Midbrain Dopaminergic Neurons ◽  
Midbrain Dopamine

Aversive memories are important for survival, and dopaminergic signaling in the hippocampus has been implicated in aversive learning. However, the source and mode of action of hippocampal dopamine remain controversial. Here, we utilize anterograde and retrograde viral tracing methods to label midbrain dopaminergic projections to the dorsal hippocampus. We identify a population of midbrain dopaminergic neurons near the border of the substantia nigra pars compacta and the lateral ventral tegmental area that sends direct projections to the dorsal hippocampus. Using optogenetic manipulations and mutant mice to control dopamine transmission in the hippocampus, we show that midbrain dopamine potently modulates aversive memory formation during encoding of contextual fear. Moreover, we demonstrate that dopaminergic transmission in the dorsal CA1 is required for the acquisition of contextual fear memories, and that this acquisition is sustained in the absence of catecholamine release from noradrenergic terminals. Our findings identify a cluster of midbrain dopamine neurons that innervate the hippocampus and show that the midbrain dopamine neuromodulation in the dorsal hippocampus is sufficient to maintain aversive memory formation.

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

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 Midbrain dopamine neurons sustain inhibitory transmission using plasma membrane uptake of GABA, not synthesis

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Nicolas X Tritsch ◽  
Won-Jong Oh ◽  
Chenghua Gu ◽  
Bernardo L Sabatini
Keyword(s):  
Dopaminergic Neurons ◽  
De Novo ◽  
Dopamine Neurons ◽  
Gaba Uptake ◽  
Projection Neurons ◽  
Dependent Manner ◽  
Gaba Transporters ◽  
Midbrain Dopamine ◽  
Nigrostriatal Dopamine Neurons ◽  
Midbrain Dopamine Neurons

Synaptic transmission between midbrain dopamine neurons and target neurons in the striatum is essential for the selection and reinforcement of movements. Recent evidence indicates that nigrostriatal dopamine neurons inhibit striatal projection neurons by releasing a neurotransmitter that activates GABAA receptors. Here, we demonstrate that this phenomenon extends to mesolimbic afferents, and confirm that the released neurotransmitter is GABA. However, the GABA synthetic enzymes GAD65 and GAD67 are not detected in midbrain dopamine neurons. Instead, these cells express the membrane GABA transporters mGAT1 (Slc6a1) and mGAT4 (Slc6a11) and inhibition of these transporters prevents GABA co-release. These findings therefore indicate that GABA co-release is a general feature of midbrain dopaminergic neurons that relies on GABA uptake from the extracellular milieu as opposed to de novo synthesis. This atypical mechanism may confer dopaminergic neurons the flexibility to differentially control GABAergic transmission in a target-dependent manner across their extensive axonal arbors.

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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