NEURAL-NETWORK OF STRUCTURES IN WHICH GABA(B) RECEPTORS REGULATE ABSENCE SEIZURES IN THE LETHARGIC (LH LH) MOUSE MODEL/

In previous work we have shown that GABA, receptors are required for e xpression of absence seizures in the lethargic (lh/lh) mouse model; th at lh/lh mice have increased numbers of GABA(B) binding sites compared to nonepileptic littermates (designated +/+); and that the magnitude of the increased number of GABA(B) receptors in lh/lh mice correlated positively with the frequency of absence seizures. We performed this s tudy to delineate the neural network in which GABA(B) receptors regula te absence seizures in lh/lh mice. We designed three successive screen s which had to be passed by a candidate neuronal population before it could be considered a member of the neural network in which GABA(B) re ceptors regulate absence seizures, First, the neuronal populations in lh/lh mice had to have enriched GABA(B) binding sites compared to homo logous populations in matched nonepileptic controls; baclofen-displace able H-3-GABA binding was measured in autoradiograms for this screen, Second, the candidate populations had to generate spike-wave discharge s (SWDs) during absence seizures in lh/lh mice; bipolar recording elec trodes implanted into candidate neuronal structures were used in this screen, Third, the candidate populations had to demonstrate GABA(B) re ceptor-mediated regulation of absence seizures in lh/lh mice; microinj ections of a GABA(B) agonist [(-)-baclofen] and antagonist (CGP 35348) were used for this screen, In this study we found that anterior ventr al lateral thalamic nucleus (VLa), nucleus reticularis thalami (NRT), nucleus reuniens (RE) passed all three screens, and hence are members of the neural network in which GABA(B) receptors regulate absence seiz ures in lh/lh mice.