Glutamatergic signaling by mesolimbic dopamine neurons in the nucleus accumbens.
Recent evidence suggests the intriguing possibility that midbrain dopaminergic (DAergic) neurons may use fast glutamatergic transmission to communicate with their postsynaptic targets. Because of technical limitations, direct demonstration of the existence of this signaling mechanism has been limited to experiments using cell culture preparations that often alter neuronal function including neurotransmitter phenotype. Consequently, it remains uncertain whether glutamatergic signaling between DAergic neurons and their postsynaptic targets exists under physiological conditions. Here, using an optogenetic approach, we provide the first conclusive demonstration that mesolimbic DAergic neurons in mice release glutamate and elicit excitatory postsynaptic responses in projection neurons of the nucleus accumbens. In addition, we describe the properties of the postsynaptic glutamatergic responses of these neurons during experimentally evoked burst firing of DAergic axons that reproduce the reward-related phasic population activity of the mesolimbic projection. These observations indicate that, in addition to DAergic mechanisms, mesolimbic reward signaling may involve glutamatergic transmission.
Tecuapetla
Fatuel
F
Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey 07102, USA.
Patel
Jyoti C
JC
Xenias
Harry
H
English
Daniel
D
Tadros
Ibrahim
I
Shah
Fulva
F
Berlin
Joshua
J
Deisseroth
Karl
K
Rice
Margaret E
ME
Tepper
James M
JM
Koos
Tibor
T
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018014:Gene Transfer Techniques; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000166:cytology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010775:Photic Stimulation / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D015259:Dopamine Agents; D008164:Luminescent Proteins; D026941:Sodium Channel Blockers; D018698:Glutamic Acid; D013779:Tetrodotoxin; D004298:Dopamine