GABAergic activation in the dorsal hippocampus in an acute pentylenetetrazol seizure model in adult rats Open Access

Weiss, Zoe Michel (2016)

Permanent URL: https://etd.library.emory.edu/concern/etds/zw12z615t?locale=en
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Abstract

The pattern of activation of GABAergic and parvalbumin (PV)-containing interneurons over time was investigated in the dentate gyrus and CA3 region of the dorsal hippocampus following pentylenetetrazol (PTZ)-induced seizures in adult rats. Sections though the dorsal hippocampus were immunostaining for c-fos, GAD67 and parvalbumin and colocalization analyzed using semi-quantitative cell counts. Overall, the expression of c-fos in the dentate gyrus and CA3 increased over time in the PTZ-treated animals. There was a significant difference between activation of GABAergic interneurons of PTZ-treated animals and controls, however, in both the dentate gyrus and CA3 GABAergic activation did not change over time. Activation of PV-containing interneurons was significantly greater in PTZ-treated animals compared to controls. However, the activation of PV-containing interneurons changed in an unexpected time-dependent manner. In the dentate gyrus, activation of PV-containing neurons was greatest at the earliest time point from the onset of behavioral seizures, and in the CA3 activation was greatest at the latest time point from the onset of behavioral seizures. At least 70% of activated neurons in the hippocampus did not express PV or GAD67, thus a majority of the activation during the induced seizures takes place in the glutamatergic neurons. These data suggest that in an acute PTZ model, targeted inhibition of the glutamatergic populations in the hippocampus would be more effective for limiting seizure propagation.

Table of Contents

Introduction…………………………………………………………………………………………………..…...1

Epilepsy and its Current Treatment………………………………………………….……….1

Optogenetics and Luminopsins………………………………………………………..………..2

The Hippocampus and Temporal Lobe Epilepsy……………………......……………….3

Pentylenetetrazol Epilepsy Model and Cellular Activation……...….……………….6

Methods……………………………………………………………………………………………………………..7

Animals……………………………………………………………………………………………………7

Seizure Induction and Perfusion………………………………………………………………..7

Immunocytochemistry……………………………………………………………………………...8

Imaging………………………………………..………………………………………………………..…9

Data Analysis…………………………………………………………………………………………..10

Results……………………………………………………………………………………………………….…..….11

PTZ induced seizures…………………………….………………………………………….…..…11

Seizure induced c-fos expression………………………………………………....……..…….11

Activation pattern in GABAergic interneurons………………….…………..…………..12

Activation pattern in parvalbumin-containing GABAergic interneurons..…...14

Discussion.……………………………………………………………………………………………….….…….16

References…………………………………………..………………………………………………………..……19

Figures and Tables…………………………………………………………………………………………........…..26

Table 1………………………………………………………………………………………..…………..26

Figure 1…………………………………...……………………………………………………………...26

Figure 2…………………………………………………………………………………………………..27

Figure 3…………………………………………………………………………………………………..28

Figure 4…………………………………………………………………………………………………..29

Figure 5…………………………………………………………………………………………………..30

Figure 6…………………………………………………………………………………………………..31

Figure 7…………………………………………………………………………………………………..32

Figure 8…………………………………………………………………………………………………..33

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