Mediodorsal Thalamus Plays a Critical Role in the Development of Limbic Motor Seizures

Abstract

Limbic motor seizures in animals, analogous to complex partial seizures in humans, result in a consistent activation of the mediodorsal thalamus (MD) and, with prolonged seizures, damage to MD. This study examined the functional role of MD in focally evoked limbic motor seizures in the rat. GABA-and glutamate (Glu)-mediated synaptic transmissions in MD were evaluated for an influence on seizures evoked from area tempestas (AT), a discrete epileptogenic site in the rostral piriform cortex.A GABA A receptor agonist, Glu receptor antagonists, or a GABA-elevating agent were focally microinfused into MD before evoking seizures by focal application of bicuculline methiodide into the ipsilateral AT. Focal pretreatment of MD with the GABA A agonist muscimol (190 pmol) protected against seizures evoked from AT. Seizure protection was also obtained with the focal application of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline (NBQX) (500 pmol), an antagonist of the AMPA subtype of Glu receptors, into MD. In contrast, focal pretreatment of MD with a competitive antagonist of the NMDA receptor 2-amino-7-phosphonoheptanoic acid (500 pmol) did not attenuate seizures. The anticonvulsant effects achieved with intra-MD injections of muscimol and NBQX were site-specific, because no seizure protection was obtained with injections placed 2 mm ventral or lateral to MD. Prolonged seizure protection was obtained following GABA elevation in MD after the application of the GABA transaminase inhibitor vigabatrin (194 nmol). These results suggest the following: (1) MD is a critical participant in the generation of seizures elicited focally from piriform cortex; (2) transmission via AMPA receptors, but not NMDA receptors, in MD regulates limbic seizure propagation; and (3) a GABA-mediated system exists within MD, the enhancement of which protects against focally evoked limbic motor seizures.

Involvement of the Thalamic Parafascicular Nucleus in Mesial Temporal Lobe Epilepsy

“…Because of the small number of structures injected or stimulated outside of the PF in each group, we cannot provide statistical analysis, but it is possible that hippocampal activity after injections or stimulations in the PF may be different from that in outside structures. Data of the midline thalamus and the mediodorsal and reuniens nuclei support this hypothesis suggesting their participation in the initiation and spread of limbic seizures (Cassidy and Gale, 1998;Bertram et al, 2001Bertram et al, , 2008.…”

Synchrony Dynamics Across Brain Structures in Limbic Epilepsy Vary Between Initiation and Termination Phases of Seizures

“…This is in agreement with other animal studies. The thalamus has been shown to be involved during the course of seizures [33] and may play a crucial role in seizure development [34]. In addition, the study of human TLE patients by Guye et al [35] showed that synchronization of signals from the thalamus and the temporal lobe structures occurs during seizures and tends to be particularly constant and marked in the last phase of the seizure.…”

Intraventricular and Intracerebral Delivery of Anti-epileptic Drugs in the Kindling Model

“…49 Also, injection of similar drugs in the ipsilateral nucleus dorsomedianus thalami inhibits generalization of limbic seizures provoked by acute application of bicuculin at the "area tempestas." 50 Motor expression of seizures was suppressed in the amygdala-kindling model in rats by continuous infusion of GABA at the motor cortex. 25 In this experiment, however, the sudden withdrawal of GABA infusion led to seizures.…”