The loss of interneuron functional diversity in the piriform cortex after induction of experimental epilepsy.
Interneuronal functional diversity is thought to be an important factor in the control of neural network oscillations in many brain regions. Specifically, interneuron action potential firing patterns are thought to modulate brain rhythms. In neurological disorders such as epilepsy where brain rhythms are significantly disturbed interneuron function is largely unexplored. Thus the purpose of this study was to examine the functional diversity of piriform cortex interneurons (PC; an area of the brain that easily supports seizures) before and after kindling-induced epilepsy. Using cluster analysis, we found five control firing behaviors. These groups were termed: non-adapting very high frequency (NAvHF), adapting high frequency (AHF), adapting low frequency (ALF), strongly adapting low frequency (sALF), and weakly adapting low frequency (wALF). A morphological analysis showed these spiking patterns were not associated with any specific interneuronal morphology although we found that most of the cells displaying NAvHF firing pattern were multipolar. After kindling about 40% of interneuronal firing pattern changed, and neither the NAvHF nor the wALF phenotypes were found. We also found that in multipolar interneurons a long-lasting potassium current was increased. A qPCR analysis indicated Kv1.6 subtype was up-regulated after kindling. An immunocytochemical analysis showed that Kv1.6 protein expression on parvalbumin (multipolar) interneurons increased by greater than 400%. We also examined whether these changes could be due to the selective death of a subset of interneurons but found that there was no change in cell number. These data show an important loss of the functional diversity of interneurons in the PC. Our data suggest that under pathophysiological condition interneurons are plastic resulting in the attenuation of high frequency network oscillations in favor of low frequency network activity. This may be an important new mechanism by which network synchrony is disturbed in epileptic seizures.
Molecular Brain Research Group, Robarts Research Institute, Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada N6A 5K8.
Cezar
C
Gavrilovici
Emily
E
Pollock
Michelle
M
Everest
Michael O
MO
Poulter
D000818:Animals; D016000:Cluster Analysis; D004195:Disease Models, Animal; D004827:Epilepsy / Q000503:physiopathology*; D007150:Immunohistochemistry; D007395:Interneurons / Q000502:physiology*; D007696:Kindling, Neurologic; D008032:Limbic System / Q000503:physiopathology*; D008297:Male; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley