Final Report Summary - MESSI (Mesocorticolimbic System: functional anatomy, drug-evoked synaptic plasticity & behavioral correlates of Synaptic Inhibition)
Our project has identified several inhibitory circuits of the mesolimbic reward system.
The first is a long range projections for inhibitroy GABA neurons from the ventral tegmental area to the nucleus accumbens. The cells are activated by a salient stimulus regardless of it valence, which leads to a strong suppression of the cholinergic tone, owing to their selective projection onto these accumbal interneurons.
The second major inhibitory population are local GABA interneurons that inhibit dopamine (DA) neurons. The DA neurons then project to the dorsal part of the medial shell of the accumbens. Our work has also identified these GABA neurons are the target of opioids, which then leads to disinihbition of the DA neurons.
The project has also provided evidence of drug-evoked synaptic plasticity of inhibitory transmission. which was expressed by changes of the presynaptic release properties.
Taken together, all three aims of the project were addressed, open the doors for future studies based on our proposed circuit model of addiction that now also integrates inhibitory transmission.
The first is a long range projections for inhibitroy GABA neurons from the ventral tegmental area to the nucleus accumbens. The cells are activated by a salient stimulus regardless of it valence, which leads to a strong suppression of the cholinergic tone, owing to their selective projection onto these accumbal interneurons.
The second major inhibitory population are local GABA interneurons that inhibit dopamine (DA) neurons. The DA neurons then project to the dorsal part of the medial shell of the accumbens. Our work has also identified these GABA neurons are the target of opioids, which then leads to disinihbition of the DA neurons.
The project has also provided evidence of drug-evoked synaptic plasticity of inhibitory transmission. which was expressed by changes of the presynaptic release properties.
Taken together, all three aims of the project were addressed, open the doors for future studies based on our proposed circuit model of addiction that now also integrates inhibitory transmission.