Behavioral and EEG effects of GABAergic manipulation of the nigro-tectal pathway in the Wistar audiogenic rat (WAR) strain II: an EEG wavelet analysis and retrograde neuronal tracer approach.
The role of the substantia nigra pars reticulata (SNPr) and superior colliculus (SC) network in rat strains susceptible to audiogenic seizures still remain underexplored in epileptology. In a previous study from our laboratory, the GABAergic drugs bicuculline (BIC) and muscimol (MUS) were microinjected into the deep layers of either the anterior SC (aSC) or the posterior SC (pSC) in animals of the Wistar audiogenic rat (WAR) strain submitted to acoustic stimulation, in which simultaneous electroencephalographic (EEG) recording of the aSC, pSC, SNPr and striatum was performed. Only MUS microinjected into the pSC blocked audiogenic seizures. In the present study, we expanded upon these previous results using the retrograde tracer Fluorogold (FG) microinjected into the aSC and pSC in conjunction with quantitative EEG analysis (wavelet transform), in the search for mechanisms associated with the susceptibility of this inbred strain to acoustic stimulation. Our hypothesis was that the WAR strain would have different connectivity between specific subareas of the superior colliculus and the SNPr when compared with resistant Wistar animals and that these connections would lead to altered behavior of this network during audiogenic seizures. Wavelet analysis showed that the only treatment with an anticonvulsant effect was MUS microinjected into the pSC region, and this treatment induced a sustained oscillation in the theta band only in the SNPr and in the pSC. These data suggest that in WAR animals, there are at least two subcortical loops and that the one involved in audiogenic seizure susceptibility appears to be the pSC-SNPr circuit. We also found that WARs presented an increase in the number of FG+ projections from the posterior SNPr to both the aSC and pSC (primarily to the pSC), with both acting as proconvulsant nuclei when compared with Wistar rats. We concluded that these two different subcortical loops within the basal ganglia are probably a consequence of the WAR genetic background.
Neuroscience and Behavioral Sciences Department, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Franco
F
Rossetti
Marcelo Cairrão Araújo
MC
Rodrigues
Simone S
SS
Marroni
Artur
A
Fernandes
Maira Licia
ML
Foresti
Rodrigo N
RN
Romcy-Pereira
Dráulio Barros
DB
de Araújo
Norberto
N
Garcia-Cairasco
D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D058256:Brain Waves / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects; D020195:Epilepsy, Reflex / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D018682:GABA Agents / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology / Q000627:therapeutic use; D009434:Neural Pathways / Q000502:physiology; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D013266:Stilbamidines; D013378:Substantia Nigra / Q000502:physiology*; D013477:Superior Colliculi / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D018682:GABA Agents; D013266:Stilbamidines; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline