Muscarinic acetylcholine receptor activation prevents disinhibition-mediated LTP in the Hippocampus
Disinhibition-mediated long-term potentiation (LTP) in the CA1 region of the hippocampus involves GABAergic synaptic plasticity at feedforward inhibitory inputs, resulting in the reduced shunting of glutamatergic excitatory currents. The GABAergic plasticity which underlies disinhibition-mediated LT...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-02-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncel.2013.00016/full |
| _version_ | 1819154658510241792 |
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| author | Petri eTakkala Melanie A Woodin |
| author_facet | Petri eTakkala Melanie A Woodin |
| author_sort | Petri eTakkala |
| collection | DOAJ |
| description | Disinhibition-mediated long-term potentiation (LTP) in the CA1 region of the hippocampus involves GABAergic synaptic plasticity at feedforward inhibitory inputs, resulting in the reduced shunting of glutamatergic excitatory currents. The GABAergic plasticity which underlies disinhibition-mediated LTP results from a Ca2+-dependent decrease in the activity of the K+-Cl- cotransporter (KCC2), depolarizing the reversal potential for GABAA receptor-mediated currents (EGABA), thereby attenuating inhibition. Muscarinic acetylcholine receptor (mAChR) activation has previously been shown to regulate classic glutamatergic LTP, modulate intracellular [Ca2+] and signaling, and facilitate the excitability of GABAergic interneurons in the CA1. Based on these effects, and the ability of mAChR activation to regulate CA1 pyramidal neuron KCC2 expression, we proposed that mAChR activation would modulate disinhibition-mediated LTP. To test this prediction, we made whole cell recordings from CA1 pyramidal neurons in hippocampal slices. Disinhibition-mediated LTP was induced using a spike timing-dependent plasticity (STDP) protocol, which involved coincident presynaptic stimulation and postsynaptic current injection (at 5 Hz for 60 seconds). We found that mAChR activation via carbachol (CCh) prevented the induction of disinhibition-mediated LTP. Moreover, in the presence of CCh, EGABA failed to depolarize following plasticity induction. Lastly, we recorded the paired-pulse ratio (PPR) during the induction of disinhibition-mediated LTP and found that in the presence of CCh, plasticity induction induced a significant paired-pulse depression. This suggests that presynaptic mAChR activation may prevent the postsynaptic expression of disinhibition-mediated LTP. |
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| format | Article |
| id | doaj.art-897b4a8913604cb3b15fbe147b894884 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-22T15:24:35Z |
| publishDate | 2013-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-897b4a8913604cb3b15fbe147b8948842022-12-21T18:21:31ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022013-02-01710.3389/fncel.2013.0001641627Muscarinic acetylcholine receptor activation prevents disinhibition-mediated LTP in the HippocampusPetri eTakkala0Melanie A Woodin1University of TorontoUniversity of TorontoDisinhibition-mediated long-term potentiation (LTP) in the CA1 region of the hippocampus involves GABAergic synaptic plasticity at feedforward inhibitory inputs, resulting in the reduced shunting of glutamatergic excitatory currents. The GABAergic plasticity which underlies disinhibition-mediated LTP results from a Ca2+-dependent decrease in the activity of the K+-Cl- cotransporter (KCC2), depolarizing the reversal potential for GABAA receptor-mediated currents (EGABA), thereby attenuating inhibition. Muscarinic acetylcholine receptor (mAChR) activation has previously been shown to regulate classic glutamatergic LTP, modulate intracellular [Ca2+] and signaling, and facilitate the excitability of GABAergic interneurons in the CA1. Based on these effects, and the ability of mAChR activation to regulate CA1 pyramidal neuron KCC2 expression, we proposed that mAChR activation would modulate disinhibition-mediated LTP. To test this prediction, we made whole cell recordings from CA1 pyramidal neurons in hippocampal slices. Disinhibition-mediated LTP was induced using a spike timing-dependent plasticity (STDP) protocol, which involved coincident presynaptic stimulation and postsynaptic current injection (at 5 Hz for 60 seconds). We found that mAChR activation via carbachol (CCh) prevented the induction of disinhibition-mediated LTP. Moreover, in the presence of CCh, EGABA failed to depolarize following plasticity induction. Lastly, we recorded the paired-pulse ratio (PPR) during the induction of disinhibition-mediated LTP and found that in the presence of CCh, plasticity induction induced a significant paired-pulse depression. This suggests that presynaptic mAChR activation may prevent the postsynaptic expression of disinhibition-mediated LTP.http://journal.frontiersin.org/Journal/10.3389/fncel.2013.00016/fullAcetylcholineHippocampusLTPSTDPNeuromodulationCA1 |
| spellingShingle | Petri eTakkala Melanie A Woodin Muscarinic acetylcholine receptor activation prevents disinhibition-mediated LTP in the Hippocampus Frontiers in Cellular Neuroscience Acetylcholine Hippocampus LTP STDP Neuromodulation CA1 |
| title | Muscarinic acetylcholine receptor activation prevents disinhibition-mediated LTP in the Hippocampus |
| title_full | Muscarinic acetylcholine receptor activation prevents disinhibition-mediated LTP in the Hippocampus |
| title_fullStr | Muscarinic acetylcholine receptor activation prevents disinhibition-mediated LTP in the Hippocampus |
| title_full_unstemmed | Muscarinic acetylcholine receptor activation prevents disinhibition-mediated LTP in the Hippocampus |
| title_short | Muscarinic acetylcholine receptor activation prevents disinhibition-mediated LTP in the Hippocampus |
| title_sort | muscarinic acetylcholine receptor activation prevents disinhibition mediated ltp in the hippocampus |
| topic | Acetylcholine Hippocampus LTP STDP Neuromodulation CA1 |
| url | http://journal.frontiersin.org/Journal/10.3389/fncel.2013.00016/full |
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