Midbrain substrates of audiogenic seizures in rats

Audiogenic seizures (AS) are a rodent model of generalized tonic-clonic seizures, induced in susceptible (S) animals by high intensity (110 dB) acoustic stimulation. Resistant (R) animals do not respond to the sound with any seizure-related behavior, but they display facial automatisms and grooming clusters. Genetic selection and neuroethology are the basic tools used in our laboratory to perform behavioral analysis of AS S and R animals. Based upon selective lesion and microinjection (GABA, clobazam, NMDA) studies of substantia nigra (SN), inferior colliculus (IC), superior colliculus (SC), and on specific knife cuts at midcollicular levels, we have suggested differential roles for these substrates in the origin and spreading of AS. The IC central nucleus is suggested to be the most critical area involved in the afferent pathway whose activation is necessary for AS origin. IC cortical nuclei seem to be the most important structures involved in the transduction of sensory to motor activity. SC, SN and other reticular subnuclei are suggested to be modulators or components of the efferent pathway. Although the midbrain is considered to be the only network necessary for acute AS origin, both emotion-linked acoustic memories and plastic changes linked to audiogenic kindling involve midbrain-forebrain connections. This paper reviews the behavioral manifestations of acute and chronic AS, our contribution to the knowledge of some AS neurobiological midbrain substrates and the suggested implications of midbrain-forebrain interactions typical of AS kindling.