Muscarinic modulation of high frequency oscillations in pedunculopontine neurons
We previously reported that persistent application of the non-specific cholinergic agonist carbachol (CAR) increased the frequency of calcium channel-mediated oscillatory activity in pedunculopontine nucleus (PPN) neurons, which we identified as dependent on voltage-gated, high-threshold P/Q-type ch...
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todo:paper_16642295_v4NOV_n_p_Kezunovic2023-10-03T16:29:03Z Muscarinic modulation of high frequency oscillations in pedunculopontine neurons Kezunovic, N. Hyde, J. Goitia, B. Bisagno, V. Urbano, F.J. Garcia-Rill, E. 5'-[β-thio] diphosphate trilithium salt 5'-[γ-thio] triphosphate trilithium salt Calcium channels Carbachol G-proteins Gamma oscillations Muscarinic receptors acetylcholine atropine calcium channel carbachol cholinergic receptor guanine nucleotide binding protein muscarinic M2 receptor potassium channel voltage gated sodium channel animal cell animal experiment article brain stem calcium current cell density controlled study dendrite electroencephalogram female high frequency oscillation male membrane potential nerve cell nerve cell membrane potential nerve cell membrane steady potential neuromodulation nonhuman patch clamp technique pedunculopontine tegmental nucleus protein function rat substantia nigra pars compacta voltage clamp technique We previously reported that persistent application of the non-specific cholinergic agonist carbachol (CAR) increased the frequency of calcium channel-mediated oscillatory activity in pedunculopontine nucleus (PPN) neurons, which we identified as dependent on voltage-gated, high-threshold P/Q-type channels. Here, we tested the hypothesis that M2 muscarinic receptors and G-proteins associated with M2 receptors mediate the increase in oscillatory frequency in PPN neurons. We found, using depolarizing ramps, that patch clamped 9-12 day old rat PPN neurons (n = 189) reached their peak oscillatory activity around -20 mV membrane potential. Acute (short duration) application of CAR blocked the oscillatory activity through M2 muscarinic receptors, an effect blocked by atropine. However, persistent (long duration) application of CAR significantly increased the frequency of oscillatory activity in PPN neurons through M2 receptors [40 ± 1 Hz (with CAR) vs. 23 ± 1 Hz (without CAR); p < 0.001]. We then tested the effects of the G-protein antagonist guanosine 5'-[β-thio] diphosphate trilithium salt (GDP-β-S), and the G-protein agonist 5'-[γ-thio] triphosphate trilithium salt (GTP-γ-S). We found, using a three-step protocol in voltage-clamp mode, that the increase in the frequency of oscillations induced by M2 cholinergic receptors was linked to a voltage-dependent G-protein mechanism. In summary, these results suggest that persistent cholinergic input creates a permissive activation state in the PPN that allows high frequency P/Q-type calcium channel-mediated gamma oscillations to occur. © 2013 Kezunovic, Hyde, Goitia, Bisagno, Urbano and Garcia-Rill. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_16642295_v4NOV_n_p_Kezunovic |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
5'-[β-thio] diphosphate trilithium salt 5'-[γ-thio] triphosphate trilithium salt Calcium channels Carbachol G-proteins Gamma oscillations Muscarinic receptors acetylcholine atropine calcium channel carbachol cholinergic receptor guanine nucleotide binding protein muscarinic M2 receptor potassium channel voltage gated sodium channel animal cell animal experiment article brain stem calcium current cell density controlled study dendrite electroencephalogram female high frequency oscillation male membrane potential nerve cell nerve cell membrane potential nerve cell membrane steady potential neuromodulation nonhuman patch clamp technique pedunculopontine tegmental nucleus protein function rat substantia nigra pars compacta voltage clamp technique |
| spellingShingle |
5'-[β-thio] diphosphate trilithium salt 5'-[γ-thio] triphosphate trilithium salt Calcium channels Carbachol G-proteins Gamma oscillations Muscarinic receptors acetylcholine atropine calcium channel carbachol cholinergic receptor guanine nucleotide binding protein muscarinic M2 receptor potassium channel voltage gated sodium channel animal cell animal experiment article brain stem calcium current cell density controlled study dendrite electroencephalogram female high frequency oscillation male membrane potential nerve cell nerve cell membrane potential nerve cell membrane steady potential neuromodulation nonhuman patch clamp technique pedunculopontine tegmental nucleus protein function rat substantia nigra pars compacta voltage clamp technique Kezunovic, N. Hyde, J. Goitia, B. Bisagno, V. Urbano, F.J. Garcia-Rill, E. Muscarinic modulation of high frequency oscillations in pedunculopontine neurons |
| topic_facet |
5'-[β-thio] diphosphate trilithium salt 5'-[γ-thio] triphosphate trilithium salt Calcium channels Carbachol G-proteins Gamma oscillations Muscarinic receptors acetylcholine atropine calcium channel carbachol cholinergic receptor guanine nucleotide binding protein muscarinic M2 receptor potassium channel voltage gated sodium channel animal cell animal experiment article brain stem calcium current cell density controlled study dendrite electroencephalogram female high frequency oscillation male membrane potential nerve cell nerve cell membrane potential nerve cell membrane steady potential neuromodulation nonhuman patch clamp technique pedunculopontine tegmental nucleus protein function rat substantia nigra pars compacta voltage clamp technique |
| description |
We previously reported that persistent application of the non-specific cholinergic agonist carbachol (CAR) increased the frequency of calcium channel-mediated oscillatory activity in pedunculopontine nucleus (PPN) neurons, which we identified as dependent on voltage-gated, high-threshold P/Q-type channels. Here, we tested the hypothesis that M2 muscarinic receptors and G-proteins associated with M2 receptors mediate the increase in oscillatory frequency in PPN neurons. We found, using depolarizing ramps, that patch clamped 9-12 day old rat PPN neurons (n = 189) reached their peak oscillatory activity around -20 mV membrane potential. Acute (short duration) application of CAR blocked the oscillatory activity through M2 muscarinic receptors, an effect blocked by atropine. However, persistent (long duration) application of CAR significantly increased the frequency of oscillatory activity in PPN neurons through M2 receptors [40 ± 1 Hz (with CAR) vs. 23 ± 1 Hz (without CAR); p < 0.001]. We then tested the effects of the G-protein antagonist guanosine 5'-[β-thio] diphosphate trilithium salt (GDP-β-S), and the G-protein agonist 5'-[γ-thio] triphosphate trilithium salt (GTP-γ-S). We found, using a three-step protocol in voltage-clamp mode, that the increase in the frequency of oscillations induced by M2 cholinergic receptors was linked to a voltage-dependent G-protein mechanism. In summary, these results suggest that persistent cholinergic input creates a permissive activation state in the PPN that allows high frequency P/Q-type calcium channel-mediated gamma oscillations to occur. © 2013 Kezunovic, Hyde, Goitia, Bisagno, Urbano and Garcia-Rill. |
| format |
JOUR |
| author |
Kezunovic, N. Hyde, J. Goitia, B. Bisagno, V. Urbano, F.J. Garcia-Rill, E. |
| author_facet |
Kezunovic, N. Hyde, J. Goitia, B. Bisagno, V. Urbano, F.J. Garcia-Rill, E. |
| author_sort |
Kezunovic, N. |
| title |
Muscarinic modulation of high frequency oscillations in pedunculopontine neurons |
| title_short |
Muscarinic modulation of high frequency oscillations in pedunculopontine neurons |
| title_full |
Muscarinic modulation of high frequency oscillations in pedunculopontine neurons |
| title_fullStr |
Muscarinic modulation of high frequency oscillations in pedunculopontine neurons |
| title_full_unstemmed |
Muscarinic modulation of high frequency oscillations in pedunculopontine neurons |
| title_sort |
muscarinic modulation of high frequency oscillations in pedunculopontine neurons |
| url |
http://hdl.handle.net/20.500.12110/paper_16642295_v4NOV_n_p_Kezunovic |
| work_keys_str_mv |
AT kezunovicn muscarinicmodulationofhighfrequencyoscillationsinpedunculopontineneurons AT hydej muscarinicmodulationofhighfrequencyoscillationsinpedunculopontineneurons AT goitiab muscarinicmodulationofhighfrequencyoscillationsinpedunculopontineneurons AT bisagnov muscarinicmodulationofhighfrequencyoscillationsinpedunculopontineneurons AT urbanofj muscarinicmodulationofhighfrequencyoscillationsinpedunculopontineneurons AT garciarille muscarinicmodulationofhighfrequencyoscillationsinpedunculopontineneurons |
| _version_ |
1807316028844146688 |