Projection-Specific Potentiation of Ventral Pallidal Glutamatergic Outputs after Abstinence from Cocaine
| Autor: | Yonatan M. Kupchik, Nimrod Bernat, Dorrit Inbar, Ava Gatterer, Kineret Inbar, Noa Nachshon, Liran A. Levi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Basal Forebrain Glutamic Acid Mice Transgenic Nucleus accumbens Biology Optogenetics Ventral pallidum 03 medical and health sciences Reward system Cocaine-Related Disorders Mice 0302 clinical medicine Reward Dopamine Recurrence Neural Pathways medicine Animals Research Articles Neurons Neuronal Plasticity General Neuroscience Long-term potentiation Conditioned place preference Substance Withdrawal Syndrome Ventral tegmental area Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure nervous system Female Erratum Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | J Neurosci |
| ISSN: | 1529-2401 |
| Popis: | The ventral pallidum (VP) is a central node in the reward system that is strongly implicated in reward and addiction. Although the majority of VP neurons are GABAergic and encode reward, recent studies revealed a novel glutamatergic neuronal population in the VP [VP neurons expressing the vesicular glutamate transporter 2 (VPVGluT2)], whose activation generates aversion. Withdrawal from drugs has been shown to induce drastic synaptic changes in neuronal populations associated with reward, such as the ventral tegmental area (VTA) or nucleus accumbens neurons, but less is known about cocaine-induced synaptic changes in neurons classically linked with aversion. Here, we demonstrate that VPVGluT2neurons contact different targets with different intensities, and that cocaine conditioned place preference (CPP) training followed by abstinence selectively potentiates their synapses on targets that encode aversion. Using whole-cell patch-clamp recordings combined with optogenetics in male and female transgenic mice, we show that VPVGluT2neurons preferentially contact aversion-related neurons, such as lateral habenula neurons and VTA GABAergic neurons, with minor input to reward-related neurons, such as VTA dopamine and VP GABA neurons. Moreover, after cocaine CPP and abstinence, the VPVGluT2input to the aversion-related structures is potentiated, whereas the input to the reward-related structures is depressed. Thus, cocaine CPP followed by abstinence may allow VPVGluT2neurons to recruit aversion-related targets more readily and therefore be part of the mechanism underlying the aversive symptoms seen after withdrawal.SIGNIFICANCE STATEMENTThe biggest problem in drug addiction is the high propensity to relapse. One central driver for relapse events is the negative aversive symptoms experienced by addicts during withdrawal. In this work, we propose a possible mechanism for the intensification of aversive feelings after withdrawal that involves the glutamatergic neurons of the ventral pallidum. We show not only that these neurons are most strongly connected to aversive targets, such as the lateral habenula, but also that, after abstinence, their synapses on aversive targets are strengthened, whereas the synapses on other rewarding targets are weakened. These data illustrate how after abstinence from cocaine, aversive pathways change in a manner that may contribute to relapse. |
| Databáze: | OpenAIRE |
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