Impaired synaptic plasticity in the surround of perinatally acquired [correction of aquired] dysplasia in rat cerebral cortex.
Freeze-lesion induced neocortical dysplasias in rats mimic numerous aspects of human polymicrogyria and are used as a model for the study of developmental migration disorders. Since memory tests have demonstrated learning deficits in rodents with neocortical malformations, we investigated the expression and properties of long-term potentiation (LTP) in neocortical slices from adult freeze-lesioned and control rats. Field potentials, recorded in layer II/III at a distance of 2-3 mm lateral to perinatally induced microgyri, were strongly enhanced following theta-burst stimulation in layer VI (amplitude: 174 +/- 4%) compared to controls (110 +/- 2%). In contrast, in layer IV of the freeze-lesioned cortex LTP could not reliably be induced. Histochemical analysis, performed to elucidate the cellular basis of the impaired plasticity, revealed diminished amounts of the GABAA-receptor subunit gamma2 in the paramicrogyral zone, likely representing a diminished GABA-ergic filter, which is thought to prevent LTP induced in layer VI under normal conditions. Cytochrome-oxidase staining after electrophysiological examination disclosed that LTP in layer IV of the freeze-lesioned cortex could only be elicited, when stimulation was applied within a preserved barrel cortex. Our study provides evidence that focal cryolesions during cortical development cause an impaired synaptic plasticity that may underlie learning disabilities.
Peters
Oliver
O
Department of Psychiatry and Psychotherapy, Charité--University Medicine Berlin, Benjamin Franklin Campus, Eschenallee 3, D-14050 Berlin, Germany. oliver.peters@charite.de
Redecker
Christoph
C
Hagemann
Georg
G
Bruehl
Claus
C
Luhmann
Heiko J
HJ
Witte
Otto W
OW
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002540:Cerebral Cortex / Q000254:growth & development* / Q000473:pathology*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology*