| The moderate severity strain of genetically epilepsy-prone rats (GEPR-3s) stereotypically exhibit generalized clonic audiogenic seizures (AGS). Repeated AGS induction (AGS kindling) induces facial and forelimb (F& F) clonus immediately following generalized clonus. I evaluated AGS neuronal network mechanisms in GEPR-3s by examining effects of focal microinjection and neuronal firing patterns in nuclei previously implicated in AGS. Microinjection of a competitive NMDA receptor antagonist, DL-2-Amino-7-phosphonoheptanoic acid (AP7) into inferior colliculus (ICc), deep layers of superior colliculus (DLSC), periaqueductal grey (PAG) or caudal pontine reticular formation (cPRF) blocked AGS, supporting these sites as requisite components of the AGS neuronal network in GEPR-3s. AP7 microinjected into amygdala (AMG) blocked AGS before and after AGS kindling. However, blockade of F&F clonus without effect on generalized clonus occurred after kindling at lower doses of AP7, suggesting that AMG is a requisite part of the neuronal network for AGS both before and after AGS kindling.; In perirhinal cortex (PRh), AP7 did not block generalized clonus, but after kindling AP7 selectively blocked F&F clonus without affecting generalized clonus, suggesting that PRh is a requisite component of the network for F&F clonus.; Significantly increased neuronal firing occurred in cPRF after AGS kindling and tonic firing were observed during AGS before kindling. Increased neuronal firing and a change to burst firing suggest AGS kindling-induced increases in cPRF excitation.; Increased AMG neuronal firing occurred after AGS kindling, indicating increased AMG neuronal excitability. Burst firing occurred during generalized and F&F clonus before and after AGS kindling, supporting a role of AMG in both seizure behaviors. Significant kindling-induced increases in PRh neuronal firing occurred, indicating kindling-induced increases in PRh neuronal excitability. A repetitive neuronal firing pattern occurred during generalized clonus before and after AGS kindling, but burst firing occurred only during F&F clonus, supporting a role for PRh in AGS after kindling.; Thus, ICc, DLSC, PAG, and cPRF are critical components of the AGS neuronal network before kindling in GEPR-3s. AMG plays a dual role in brainstem- and forebrain-driven seizure behaviors, and PRh is a requisite part of the neuronal network only after AGS kindling. |
