Loss of perikaryal parvalbumin immunoreactivity from surviving GABAergic neurons in the CA1 field of epileptic gerbils.
The Mongolian gerbil (Meriones unguiculatus) is known as a genetic model of epilepsy. Seizure behavior ranges from subtle events like arrest of motor activity and facial spasms to grand mal seizures followed by automatisms. Exploratory behavior in a stressful situation represents the most effective environment for provoking seizures in gerbils. Modifications of the inhibitory hippocampal circuits have been suggested as a cause of seizure susceptibility in the gerbil. This study presents a quantitative analysis of the hippocampal parvalbumin (PV)-immunoreactive and gamma-aminobutyric acid (GABA)-immunoreactive neurons in gerbils whose seizure sensitivity had been scored. PV is a cytosolic calcium-binding protein synthesized by a subpopulation of GABAergic neurons and thought to be responsible for the fast spiking capability of this subset of neurons. We show that the number of PV-immunoreactive neurons in the CA1 field of the gerbil hippocampus decreases in repeatedly seizing animals as compared to non-seizing controls. The lowest density of PV-immunoreactive neurons was observed 1 hour after the last generalized seizure. No changes in the density of GABA-immunoreactive neurons in field CA1 paralleled the obvious loss of perikaryal PV-immunoreactivity. The CA1 field represents the final output region to extrahippocampal brain areas, and its recruitment or not into seizure activity is crucial for the spreading of hippocampal discharges to the adjacent neocortex. A reduction of such a calcium-buffering system in the soma and dendrites may affect the spike characteristics of PV-containing GABAergic neurons and may alter their response to glutamatergic transmission. A reduced inhibitory control of pyramidal cells may ensue, facilitating neuronal excitability as a result.
Scotti
A L
AL
Institute of Anatomy, University of Basel, Switzerland.
Bollag
O
O
Kalt
G
G
Nitsch
C
C
D000818:Animals; D001143:Arousal / Q000502:physiology; D004827:Epilepsy / Q000378:metabolism* / Q000473:pathology; D004830:Epilepsy, Tonic-Clonic / Q000378:metabolism / Q000473:pathology; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007696:Kindling, Neurologic / Q000502:physiology; D008297:Male; D009207:Myoclonus / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid