Nicotine aversion is mediated by GABAergic interpeduncular nucleus inputs to laterodorsal tegmentum
| Autor: | Daniel S. McGehee, Katie Long, Jordan G. McCall, Fili Bogdanic, Ream Al-Hasani, Daniel F. Gill, Shannon L. Wolfman, Michael R. Bruchas |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Nicotine Interpeduncular nucleus Tegmentum Mesencephali Interpeduncular Nucleus Science Gene Expression General Physics and Astronomy Optogenetics Article General Biochemistry Genetics and Molecular Biology Stereotaxic Techniques Mice 03 medical and health sciences 0302 clinical medicine Channelrhodopsins Reward Neural Pathways Avoidance Learning medicine Animals Transgenes GABAergic Neurons Axon lcsh:Science Habenula Multidisciplinary Chemistry General Chemistry Electrodes Implanted 3. Good health Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Synapses Stereotaxic technique Synaptic plasticity Excitatory postsynaptic potential GABAergic lcsh:Q Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-11 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Nicotine use can lead to dependence through complex processes that are regulated by both its rewarding and aversive effects. Recent studies show that aversive nicotine doses activate excitatory inputs to the interpeduncular nucleus (IPN) from the medial habenula (MHb), but the downstream targets of the IPN that mediate aversion are unknown. Here we show that IPN projections to the laterodorsal tegmentum (LDTg) are GABAergic using optogenetics in tissue slices from mouse brain. Selective stimulation of these IPN axon terminals in LDTg in vivo elicits avoidance behavior, suggesting that these projections contribute to aversion. Nicotine modulates these synapses in a concentration-dependent manner, with strong enhancement only seen at higher concentrations that elicit aversive responses in behavioral tests. Optogenetic inhibition of the IPN–LDTg connection blocks nicotine conditioned place aversion, suggesting that the IPN–LDTg connection is a critical part of the circuitry that mediates the aversive effects of nicotine. Despite its known effects in brain reward centers, nicotine can be aversive in high doses. Here, the authors show that nicotine aversion depends on low-affinity nicotinic acetylcholine receptors expressed on projections from the interpeduncular nucleus to the laterodorsal tegmentum. |
| Databáze: | OpenAIRE |
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