Differential Contribution of Ca2+-Dependent Mechanisms to Hyperexcitability in Layer V Neurons of the Medial Entorhinal Cortex
Temporal lobe epilepsy is characterized by recurrent seizures in one or both temporal lobes of the brain; some in vitro models show that epileptiform discharges initiate in entorhinal layer V neurons and then spread into other areas of the temporal lobe. We previously found that, in the presence of...
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2017.00182/full |
| _version_ | 1819263227961278464 |
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| author | Eric C. Lin Crescent L. Combe Sonia Gasparini Sonia Gasparini |
| author_facet | Eric C. Lin Crescent L. Combe Sonia Gasparini Sonia Gasparini |
| author_sort | Eric C. Lin |
| collection | DOAJ |
| description | Temporal lobe epilepsy is characterized by recurrent seizures in one or both temporal lobes of the brain; some in vitro models show that epileptiform discharges initiate in entorhinal layer V neurons and then spread into other areas of the temporal lobe. We previously found that, in the presence of GABAA receptor antagonists, stimulation of afferent fibers, terminating both at proximal and distal dendritic locations, initiated hyperexcitable bursts in layer V medial entorhinal neurons. We investigated the differential contribution of Ca2+-dependent mechanisms to the plateaus underlying these bursts at proximal and distal synapses. We found that the NMDA glutamatergic antagonist D,L-2-amino-5-phosphonovaleric acid (APV; 50 μM) reduced both the area and duration of the bursts at both proximal and distal synapses by about half. The L-type Ca2+ channel blocker nimodipine (10 μM) and the R- and T-type Ca2+ channel blocker NiCl2 (200 μM) decreased the area of the bursts to a lesser extent; none of these effects appeared to be location-dependent. Remarkably, the perfusion of flufenamic acid (FFA; 100 μM), to block Ca2+-activated non-selective cation currents (ICAN) mediated by transient receptor potential (TRP) channels, had a location-dependent effect, by abolishing burst firing and switching the suprathreshold response to a single action potential (AP) for proximal stimulation, but only minimally affecting the bursts evoked by distal stimulation. A similar outcome was found when FFA was pressure-applied locally around the proximal dendrite of the recorded neurons and in the presence of a selective blocker of melastatin TRP (TRPM) channels, 9-phenanthrol (100 μM), whereas a selective blocker of canonical TRP (TRPC) channels, SKF 96365, did not affect the bursts. These results indicate that different mechanisms might contribute to the initiation of hyperexcitability in layer V neurons at proximal and distal synapses and could shed light on the initiation of epileptiform activity in the entorhinal cortex. |
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| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-23T20:10:15Z |
| publishDate | 2017-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-3efa3e735d904d19beb4ffe458e2322f2022-12-21T17:32:49ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022017-06-011110.3389/fncel.2017.00182250031Differential Contribution of Ca2+-Dependent Mechanisms to Hyperexcitability in Layer V Neurons of the Medial Entorhinal CortexEric C. Lin0Crescent L. Combe1Sonia Gasparini2Sonia Gasparini3Neuroscience Center of Excellence, Louisiana State University Health Sciences CenterNew Orleans, LA, United StatesNeuroscience Center of Excellence, Louisiana State University Health Sciences CenterNew Orleans, LA, United StatesNeuroscience Center of Excellence, Louisiana State University Health Sciences CenterNew Orleans, LA, United StatesDepartment of Cell Biology and Anatomy, Louisiana State University Health Sciences CenterNew Orleans, LA, United StatesTemporal lobe epilepsy is characterized by recurrent seizures in one or both temporal lobes of the brain; some in vitro models show that epileptiform discharges initiate in entorhinal layer V neurons and then spread into other areas of the temporal lobe. We previously found that, in the presence of GABAA receptor antagonists, stimulation of afferent fibers, terminating both at proximal and distal dendritic locations, initiated hyperexcitable bursts in layer V medial entorhinal neurons. We investigated the differential contribution of Ca2+-dependent mechanisms to the plateaus underlying these bursts at proximal and distal synapses. We found that the NMDA glutamatergic antagonist D,L-2-amino-5-phosphonovaleric acid (APV; 50 μM) reduced both the area and duration of the bursts at both proximal and distal synapses by about half. The L-type Ca2+ channel blocker nimodipine (10 μM) and the R- and T-type Ca2+ channel blocker NiCl2 (200 μM) decreased the area of the bursts to a lesser extent; none of these effects appeared to be location-dependent. Remarkably, the perfusion of flufenamic acid (FFA; 100 μM), to block Ca2+-activated non-selective cation currents (ICAN) mediated by transient receptor potential (TRP) channels, had a location-dependent effect, by abolishing burst firing and switching the suprathreshold response to a single action potential (AP) for proximal stimulation, but only minimally affecting the bursts evoked by distal stimulation. A similar outcome was found when FFA was pressure-applied locally around the proximal dendrite of the recorded neurons and in the presence of a selective blocker of melastatin TRP (TRPM) channels, 9-phenanthrol (100 μM), whereas a selective blocker of canonical TRP (TRPC) channels, SKF 96365, did not affect the bursts. These results indicate that different mechanisms might contribute to the initiation of hyperexcitability in layer V neurons at proximal and distal synapses and could shed light on the initiation of epileptiform activity in the entorhinal cortex.http://journal.frontiersin.org/article/10.3389/fncel.2017.00182/fullentorhinal cortexdendritesTRP channelsexcitatory transmissionpatch clamp electrophysiologyepileptogenesis |
| spellingShingle | Eric C. Lin Crescent L. Combe Sonia Gasparini Sonia Gasparini Differential Contribution of Ca2+-Dependent Mechanisms to Hyperexcitability in Layer V Neurons of the Medial Entorhinal Cortex Frontiers in Cellular Neuroscience entorhinal cortex dendrites TRP channels excitatory transmission patch clamp electrophysiology epileptogenesis |
| title | Differential Contribution of Ca2+-Dependent Mechanisms to Hyperexcitability in Layer V Neurons of the Medial Entorhinal Cortex |
| title_full | Differential Contribution of Ca2+-Dependent Mechanisms to Hyperexcitability in Layer V Neurons of the Medial Entorhinal Cortex |
| title_fullStr | Differential Contribution of Ca2+-Dependent Mechanisms to Hyperexcitability in Layer V Neurons of the Medial Entorhinal Cortex |
| title_full_unstemmed | Differential Contribution of Ca2+-Dependent Mechanisms to Hyperexcitability in Layer V Neurons of the Medial Entorhinal Cortex |
| title_short | Differential Contribution of Ca2+-Dependent Mechanisms to Hyperexcitability in Layer V Neurons of the Medial Entorhinal Cortex |
| title_sort | differential contribution of ca2 dependent mechanisms to hyperexcitability in layer v neurons of the medial entorhinal cortex |
| topic | entorhinal cortex dendrites TRP channels excitatory transmission patch clamp electrophysiology epileptogenesis |
| url | http://journal.frontiersin.org/article/10.3389/fncel.2017.00182/full |
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