Direct and indirect control of orexin/hypocretin neurons by glycine receptors.
Hypothalamic hypocretin/orexin (hcrt/orx) neurons promote arousal and reward seeking, while reduction in their activity has been linked to narcolepsy, obesity and depression. However, the mechanisms influencing the activity of hcrt/orx networks in situ are not fully understood. Here we show that gly...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1826306785443577856 |
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| author | Karnani, M Venner, A Jensen, LT Fugger, L Burdakov, D |
| author_facet | Karnani, M Venner, A Jensen, LT Fugger, L Burdakov, D |
| author_sort | Karnani, M |
| collection | OXFORD |
| description | Hypothalamic hypocretin/orexin (hcrt/orx) neurons promote arousal and reward seeking, while reduction in their activity has been linked to narcolepsy, obesity and depression. However, the mechanisms influencing the activity of hcrt/orx networks in situ are not fully understood. Here we show that glycine, a neurotransmitter best known for its actions in the brainstem and spinal cord, elicits dose dependent postsynaptic Cl⁻ currents in hcrt/orx cells in acute mouse brain slices. The effect was blocked by the glycine receptor (GLyR) antagonist strychnine and mimicked by the GlyR agonist alanine. Postsynaptic GlyRs on hcrt/orx cells remained functional during both early postnatal and adult periods, and gramicidin-perforated patch-clamp recordings revealed that they progressively switch from excitatory to inhibitory during the first two postnatal weeks. The pharmacological profile of the glycine response suggested that developed hcrt/orx neurons contain α/β-heteromeric GlyRs that lack α2-subunits, whereas α2-subunits, whereas α2-subunits are present in early postnatal hcrt/orx neurons. All postsynaptic currents (PSCs) in developed hcrt/orx cells were blocked by inhibitors of GABA and glutamate receptors, with no evidence of GlyR-mediated PSCs. However, the frequency but not amplitude of miniature PSCs was reduced by strychnine and increased by glycine in ~50% of hcrt/orx neurons. Together, these results provide the first evidence for functional GlyRs in identified hcrt/orx circuits and suggest that the activity of developed hcrt/orx cells is regulated by two GlyR pools: inhibitory extrasynaptic GlyRs located on all hcrt/orx cells and excitatory GlyRs located on presynaptic terminals contacting some hcrt/orx cells. |
| first_indexed | 2024-03-07T06:53:11Z |
| format | Journal article |
| id | oxford-uuid:fd37f410-c477-49b4-a415-01ea3debdd3e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:53:11Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:fd37f410-c477-49b4-a415-01ea3debdd3e2022-03-27T13:27:17ZDirect and indirect control of orexin/hypocretin neurons by glycine receptors.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fd37f410-c477-49b4-a415-01ea3debdd3eEnglishSymplectic Elements at Oxford2011Karnani, MVenner, AJensen, LTFugger, LBurdakov, DHypothalamic hypocretin/orexin (hcrt/orx) neurons promote arousal and reward seeking, while reduction in their activity has been linked to narcolepsy, obesity and depression. However, the mechanisms influencing the activity of hcrt/orx networks in situ are not fully understood. Here we show that glycine, a neurotransmitter best known for its actions in the brainstem and spinal cord, elicits dose dependent postsynaptic Cl⁻ currents in hcrt/orx cells in acute mouse brain slices. The effect was blocked by the glycine receptor (GLyR) antagonist strychnine and mimicked by the GlyR agonist alanine. Postsynaptic GlyRs on hcrt/orx cells remained functional during both early postnatal and adult periods, and gramicidin-perforated patch-clamp recordings revealed that they progressively switch from excitatory to inhibitory during the first two postnatal weeks. The pharmacological profile of the glycine response suggested that developed hcrt/orx neurons contain α/β-heteromeric GlyRs that lack α2-subunits, whereas α2-subunits, whereas α2-subunits are present in early postnatal hcrt/orx neurons. All postsynaptic currents (PSCs) in developed hcrt/orx cells were blocked by inhibitors of GABA and glutamate receptors, with no evidence of GlyR-mediated PSCs. However, the frequency but not amplitude of miniature PSCs was reduced by strychnine and increased by glycine in ~50% of hcrt/orx neurons. Together, these results provide the first evidence for functional GlyRs in identified hcrt/orx circuits and suggest that the activity of developed hcrt/orx cells is regulated by two GlyR pools: inhibitory extrasynaptic GlyRs located on all hcrt/orx cells and excitatory GlyRs located on presynaptic terminals contacting some hcrt/orx cells. |
| spellingShingle | Karnani, M Venner, A Jensen, LT Fugger, L Burdakov, D Direct and indirect control of orexin/hypocretin neurons by glycine receptors. |
| title | Direct and indirect control of orexin/hypocretin neurons by glycine receptors. |
| title_full | Direct and indirect control of orexin/hypocretin neurons by glycine receptors. |
| title_fullStr | Direct and indirect control of orexin/hypocretin neurons by glycine receptors. |
| title_full_unstemmed | Direct and indirect control of orexin/hypocretin neurons by glycine receptors. |
| title_short | Direct and indirect control of orexin/hypocretin neurons by glycine receptors. |
| title_sort | direct and indirect control of orexin hypocretin neurons by glycine receptors |
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