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Status Epilepticus Induced Spontaneous Dentate Gyrus Spikes: In Vivo Current Source Density Analysis.

Flynn SP, Barriere S, Barrier S, Scott RC, Lenck-Santini PP, Holmes GL - PLoS ONE (2015)

Bottom Line: DS frequency was significantly increased in pilocarpine-treated animals compared to controls.DS were associated with an increase in multiunit activity in the granule cell layer, but no change in CA1.These results suggest that following SE there is an increase in DS activity, potentially arising from hyperexcitability along the hippocampal-entorhinal pathway or within the dentate gyrus itself.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, United States of America.

ABSTRACT
The dentate gyrus is considered to function as an inhibitory gate limiting excitatory input to the hippocampus. Following status epilepticus (SE), this gating function is reduced and granule cells become hyper-excitable. Dentate spikes (DS) are large amplitude potentials observed in the dentate gyrus (DG) of normal animals. DS are associated with membrane depolarization of granule cells, increased activity of hilar interneurons and suppression of CA3 and CA1 pyramidal cell firing. Therefore, DS could act as an anti-excitatory mechanism. Because of the altered gating function of the dentate gyrus following SE, we sought to investigate how DS are affected following pilocarpine-induced SE. Two weeks following lithium-pilocarpine SE induction, hippocampal EEG was recorded in male Sprague-Dawley rats with 16-channel silicon probes under urethane anesthesia. Probes were placed dorso-ventrally to encompass either CA1-CA3 or CA1-DG layers. Large amplitude spikes were detected from EEG recordings and subject to current source density analysis. Probe placement was verified histologically to evaluate the anatomical localization of current sinks and the origin of DS. In 9 of 11 pilocarpine-treated animals and two controls, DS were confirmed with large current sinks in the molecular layer of the dentate gyrus. DS frequency was significantly increased in pilocarpine-treated animals compared to controls. Additionally, in pilocarpine-treated animals, DS displayed current sinks in the outer, middle and/or inner molecular layers. However, there was no difference in the frequency of events when comparing between layers. This suggests that following SE, DS can be generated by input from medial and lateral entorhinal cortex, or within the dentate gyrus. DS were associated with an increase in multiunit activity in the granule cell layer, but no change in CA1. These results suggest that following SE there is an increase in DS activity, potentially arising from hyperexcitability along the hippocampal-entorhinal pathway or within the dentate gyrus itself.

No MeSH data available.


Related in: MedlinePlus

Waveform and CSD plots of identified spikes in control and pilocarpine-treated animals.In the top panel all individual events were overlaid and aligned to the peak spike amplitude. In the bottom panel an average of the EEG traces was shown overlaid on a CSD plot displaying current sinks (blue) and current sources (red). In both panels on the y-axis the anatomical location of each of the 16-laminar (100 μm spacing) EEG traces was shown. A) DS observed in control animals (n = 8 spikes), B) Pilocarpine-induced DS (n = 40), C) Non-Reversing spikes in the CA1-DG plane (n = 58), D) Population events with a reversal in CA1 SL-M (n = 35) E) Events recorded in the CA1-CA3 pane (n = 47). F) Frequency of all DS in control (black) and pilocarpine (grey) treated animals. Frequency of DS in pilocarpine-treated animals was further segregated based on location of current sink in the dentate molecular layer. No significant difference was observed between the frequencies of DS at each layer of the molecular layer. SO–stratum oriens, P–CA1 pyramidal cell layer, SR–stratum radiatum, SL-M–stratum lacunosum moleculare, OML–outer molecular layer of the dentate gyrus, MML–middle molecular layer of the dentate gyrus, IML–inner molecular layer of the dentate gyrus, GCL–granule cell layer, H–hilus, CA3 –CA3 pyramidal cell layer, AH–above hippocampus, ML–molecular layer, TH–thalamus.
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pone.0132630.g003: Waveform and CSD plots of identified spikes in control and pilocarpine-treated animals.In the top panel all individual events were overlaid and aligned to the peak spike amplitude. In the bottom panel an average of the EEG traces was shown overlaid on a CSD plot displaying current sinks (blue) and current sources (red). In both panels on the y-axis the anatomical location of each of the 16-laminar (100 μm spacing) EEG traces was shown. A) DS observed in control animals (n = 8 spikes), B) Pilocarpine-induced DS (n = 40), C) Non-Reversing spikes in the CA1-DG plane (n = 58), D) Population events with a reversal in CA1 SL-M (n = 35) E) Events recorded in the CA1-CA3 pane (n = 47). F) Frequency of all DS in control (black) and pilocarpine (grey) treated animals. Frequency of DS in pilocarpine-treated animals was further segregated based on location of current sink in the dentate molecular layer. No significant difference was observed between the frequencies of DS at each layer of the molecular layer. SO–stratum oriens, P–CA1 pyramidal cell layer, SR–stratum radiatum, SL-M–stratum lacunosum moleculare, OML–outer molecular layer of the dentate gyrus, MML–middle molecular layer of the dentate gyrus, IML–inner molecular layer of the dentate gyrus, GCL–granule cell layer, H–hilus, CA3 –CA3 pyramidal cell layer, AH–above hippocampus, ML–molecular layer, TH–thalamus.

Mentions: Recordings in the hippocampal formation with 16-channel silicon probes were performed in control (n = 3) and pilocarpine-treated (n = 11) animals and analyzed for large amplitude population events. Events were classified based on 1) the orientation of the probe within the hippocampus; and 2) the anatomical location of the major current sink. In control animals, large amplitude (1343.9 ± 88.3 μV) spikes were observed when probes were placed along the dorsal-ventral axis containing CA1 and the dentate gyrus. These events were identical to previously described DS with a positive going potential within the dentate gyrus as well as a phase reversal and current sink in the molecular layer of the dentate gyrus (Fig 3A).


Status Epilepticus Induced Spontaneous Dentate Gyrus Spikes: In Vivo Current Source Density Analysis.

Flynn SP, Barriere S, Barrier S, Scott RC, Lenck-Santini PP, Holmes GL - PLoS ONE (2015)

Waveform and CSD plots of identified spikes in control and pilocarpine-treated animals.In the top panel all individual events were overlaid and aligned to the peak spike amplitude. In the bottom panel an average of the EEG traces was shown overlaid on a CSD plot displaying current sinks (blue) and current sources (red). In both panels on the y-axis the anatomical location of each of the 16-laminar (100 μm spacing) EEG traces was shown. A) DS observed in control animals (n = 8 spikes), B) Pilocarpine-induced DS (n = 40), C) Non-Reversing spikes in the CA1-DG plane (n = 58), D) Population events with a reversal in CA1 SL-M (n = 35) E) Events recorded in the CA1-CA3 pane (n = 47). F) Frequency of all DS in control (black) and pilocarpine (grey) treated animals. Frequency of DS in pilocarpine-treated animals was further segregated based on location of current sink in the dentate molecular layer. No significant difference was observed between the frequencies of DS at each layer of the molecular layer. SO–stratum oriens, P–CA1 pyramidal cell layer, SR–stratum radiatum, SL-M–stratum lacunosum moleculare, OML–outer molecular layer of the dentate gyrus, MML–middle molecular layer of the dentate gyrus, IML–inner molecular layer of the dentate gyrus, GCL–granule cell layer, H–hilus, CA3 –CA3 pyramidal cell layer, AH–above hippocampus, ML–molecular layer, TH–thalamus.
© Copyright Policy
Related In: Results  -  Collection

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pone.0132630.g003: Waveform and CSD plots of identified spikes in control and pilocarpine-treated animals.In the top panel all individual events were overlaid and aligned to the peak spike amplitude. In the bottom panel an average of the EEG traces was shown overlaid on a CSD plot displaying current sinks (blue) and current sources (red). In both panels on the y-axis the anatomical location of each of the 16-laminar (100 μm spacing) EEG traces was shown. A) DS observed in control animals (n = 8 spikes), B) Pilocarpine-induced DS (n = 40), C) Non-Reversing spikes in the CA1-DG plane (n = 58), D) Population events with a reversal in CA1 SL-M (n = 35) E) Events recorded in the CA1-CA3 pane (n = 47). F) Frequency of all DS in control (black) and pilocarpine (grey) treated animals. Frequency of DS in pilocarpine-treated animals was further segregated based on location of current sink in the dentate molecular layer. No significant difference was observed between the frequencies of DS at each layer of the molecular layer. SO–stratum oriens, P–CA1 pyramidal cell layer, SR–stratum radiatum, SL-M–stratum lacunosum moleculare, OML–outer molecular layer of the dentate gyrus, MML–middle molecular layer of the dentate gyrus, IML–inner molecular layer of the dentate gyrus, GCL–granule cell layer, H–hilus, CA3 –CA3 pyramidal cell layer, AH–above hippocampus, ML–molecular layer, TH–thalamus.
Mentions: Recordings in the hippocampal formation with 16-channel silicon probes were performed in control (n = 3) and pilocarpine-treated (n = 11) animals and analyzed for large amplitude population events. Events were classified based on 1) the orientation of the probe within the hippocampus; and 2) the anatomical location of the major current sink. In control animals, large amplitude (1343.9 ± 88.3 μV) spikes were observed when probes were placed along the dorsal-ventral axis containing CA1 and the dentate gyrus. These events were identical to previously described DS with a positive going potential within the dentate gyrus as well as a phase reversal and current sink in the molecular layer of the dentate gyrus (Fig 3A).

Bottom Line: DS frequency was significantly increased in pilocarpine-treated animals compared to controls.DS were associated with an increase in multiunit activity in the granule cell layer, but no change in CA1.These results suggest that following SE there is an increase in DS activity, potentially arising from hyperexcitability along the hippocampal-entorhinal pathway or within the dentate gyrus itself.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, United States of America.

ABSTRACT
The dentate gyrus is considered to function as an inhibitory gate limiting excitatory input to the hippocampus. Following status epilepticus (SE), this gating function is reduced and granule cells become hyper-excitable. Dentate spikes (DS) are large amplitude potentials observed in the dentate gyrus (DG) of normal animals. DS are associated with membrane depolarization of granule cells, increased activity of hilar interneurons and suppression of CA3 and CA1 pyramidal cell firing. Therefore, DS could act as an anti-excitatory mechanism. Because of the altered gating function of the dentate gyrus following SE, we sought to investigate how DS are affected following pilocarpine-induced SE. Two weeks following lithium-pilocarpine SE induction, hippocampal EEG was recorded in male Sprague-Dawley rats with 16-channel silicon probes under urethane anesthesia. Probes were placed dorso-ventrally to encompass either CA1-CA3 or CA1-DG layers. Large amplitude spikes were detected from EEG recordings and subject to current source density analysis. Probe placement was verified histologically to evaluate the anatomical localization of current sinks and the origin of DS. In 9 of 11 pilocarpine-treated animals and two controls, DS were confirmed with large current sinks in the molecular layer of the dentate gyrus. DS frequency was significantly increased in pilocarpine-treated animals compared to controls. Additionally, in pilocarpine-treated animals, DS displayed current sinks in the outer, middle and/or inner molecular layers. However, there was no difference in the frequency of events when comparing between layers. This suggests that following SE, DS can be generated by input from medial and lateral entorhinal cortex, or within the dentate gyrus. DS were associated with an increase in multiunit activity in the granule cell layer, but no change in CA1. These results suggest that following SE there is an increase in DS activity, potentially arising from hyperexcitability along the hippocampal-entorhinal pathway or within the dentate gyrus itself.

No MeSH data available.


Related in: MedlinePlus