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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

Perievent Time Histogram and z-scores of multiunit activity in the hippocampus during DS.MUA activity and z score of A) CA1 pyramidal cell layer and B) dentate granule cell layer in control animals. MUA activity and z score of C) CA1 pyramidal cell layer and D) dentate granule cell layer in pilocarpine-treated animals. The peak amplitude of DS was locked to time zero, depicted by the vertical dashed red line, in all perievent time histograms. Horizontal dashed red lines in z score plots indicate a z score of 3. No significant increase in MUA was seen in the CA1 pyramidal cell layer in either control or pilocarpine-treated animals. However, in both groups a significant increase in MUA, demonstrated by z-scores ≥3, was observed 5ms before and after DS.
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pone.0132630.g004: Perievent Time Histogram and z-scores of multiunit activity in the hippocampus during DS.MUA activity and z score of A) CA1 pyramidal cell layer and B) dentate granule cell layer in control animals. MUA activity and z score of C) CA1 pyramidal cell layer and D) dentate granule cell layer in pilocarpine-treated animals. The peak amplitude of DS was locked to time zero, depicted by the vertical dashed red line, in all perievent time histograms. Horizontal dashed red lines in z score plots indicate a z score of 3. No significant increase in MUA was seen in the CA1 pyramidal cell layer in either control or pilocarpine-treated animals. However, in both groups a significant increase in MUA, demonstrated by z-scores ≥3, was observed 5ms before and after DS.

Mentions: Multiunit activity in the CA1 pyramidal cell layer showed no change in activity, as accessed by z-score, across the time period analyzed in both control and pilocarpine-treated animals, suggesting CA1 pyramidal cells were not affected by DS (Fig 4A and 4C). However, in the dentate granule cell layer in the two control animals with DS and 8 of the 9 pilocarpine-treated animals with DS, multiunit activity increased 5 ms before (Control: z-score = 3.95 ± 0.18; Pilocarpine: z-score = 4.52 ± 0.47) and 5 ms after (Control: z-score = 3.40 ± 0.40; Pilocarpine: z-score = 4.85 ± 0.56) the peak amplitude of the dentate spike, suggesting an event related increase in granule cell layer activity (Fig 4B and 4D).


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)

Perievent Time Histogram and z-scores of multiunit activity in the hippocampus during DS.MUA activity and z score of A) CA1 pyramidal cell layer and B) dentate granule cell layer in control animals. MUA activity and z score of C) CA1 pyramidal cell layer and D) dentate granule cell layer in pilocarpine-treated animals. The peak amplitude of DS was locked to time zero, depicted by the vertical dashed red line, in all perievent time histograms. Horizontal dashed red lines in z score plots indicate a z score of 3. No significant increase in MUA was seen in the CA1 pyramidal cell layer in either control or pilocarpine-treated animals. However, in both groups a significant increase in MUA, demonstrated by z-scores ≥3, was observed 5ms before and after DS.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492740&req=5

pone.0132630.g004: Perievent Time Histogram and z-scores of multiunit activity in the hippocampus during DS.MUA activity and z score of A) CA1 pyramidal cell layer and B) dentate granule cell layer in control animals. MUA activity and z score of C) CA1 pyramidal cell layer and D) dentate granule cell layer in pilocarpine-treated animals. The peak amplitude of DS was locked to time zero, depicted by the vertical dashed red line, in all perievent time histograms. Horizontal dashed red lines in z score plots indicate a z score of 3. No significant increase in MUA was seen in the CA1 pyramidal cell layer in either control or pilocarpine-treated animals. However, in both groups a significant increase in MUA, demonstrated by z-scores ≥3, was observed 5ms before and after DS.
Mentions: Multiunit activity in the CA1 pyramidal cell layer showed no change in activity, as accessed by z-score, across the time period analyzed in both control and pilocarpine-treated animals, suggesting CA1 pyramidal cells were not affected by DS (Fig 4A and 4C). However, in the dentate granule cell layer in the two control animals with DS and 8 of the 9 pilocarpine-treated animals with DS, multiunit activity increased 5 ms before (Control: z-score = 3.95 ± 0.18; Pilocarpine: z-score = 4.52 ± 0.47) and 5 ms after (Control: z-score = 3.40 ± 0.40; Pilocarpine: z-score = 4.85 ± 0.56) the peak amplitude of the dentate spike, suggesting an event related increase in granule cell layer activity (Fig 4B and 4D).

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