Interruption of the connections of the mammillary bodies protects against generalized pentylenetetrazol seizures in guinea pigs

Abstract

Electrolytic lesions in the anterior and mid-diencephalon and ventral midbrain in guinea pigs were produced to examine the effects of interruption of the fornix (FX), mammillothalamic tracts (MT), and mammillary peduncles (MP), respectively, on the expression of pentylenetetrazol (PTZ) seizures. As a group, all mid-diencephalic lesioned animals had some degree of protection from the electroencephalographic and behavioral convulsant and lethal effects of the drug. Through a composite volume analysis of protected versus unprotected animals, as well as a retrospective comparison between MT and non-MT lesioned animals, it was demonstrated that small mid-diencephalic lesions incorporating only the MTs and their immediate vicinity were capable of completely preventing the convulsant and lethal effects of PTZ. Lesions of the FX and MP were also protective against PTZ seizures but to a lesser degree than the MT lesions.These results demonstrate that the major afferent and efferent connections of the mammillary bodies are involved in expressing PTZ seizure activity and suggest that the MT may be the major pathway mediating paroxysmal activity from brain stem to the thalamus.The expression of generalized seizures is characterized by bilateral and synchronous activation of cortical and subcortical brain regions. Although the functional anatomy of this convulsive process is yet unclear, substantial evidence suggests that subcortical brain regions, through their widespread cortical connections, play a major role in the propagation and perhaps initiation of these attacks. Early studies demonstrated numerous facilitatory and inhibitory influences on seizure activity in both the brain stem and diencephalon (Morison and Dempsey, 1942;Jasper and Droogleever-Fortuyn, 1946;Hunter and Jasper, 1949; Ingvar, 1955a, b;Ralston and Ajmone-Marsan, 1956;Kriendler et al., 1958;Andy and Mukawa, 1959; Bergman et al., 1963;Guerrero-Figueroa et al., 1963;Weir, 1964) and suggested important roles for diffusely organized regions such as the reticular formations of the pons, mesencephalon, and thalamus. Specific areas of the subcortex have also been associated with seizure mechanisms, including the hypothalamus (Murphy and Gellhorn, 1945;Jasper and Droogleever-Fortuyn, 1946; Green and Received Jan. 13, 1986; revised Aug. 28, 1986; accepted Sept. 4, 1986 (Jinnai, 1966;Jinnai et al., 1969;Jinnai and Mukawa, 1970), substantia nigra (Iadarola and Gale, 1982;Garant and Gale, 1983;Gonzalez and Hettinger, 1984; McNamara et al., 1983McNamara et al., , 1984, and several thalamic nuclei (Mullen et al., 1967;Jinnai et al., 1969;Feeney and Gullotta, 1972;Kusske et al., 1972;Van Straaten, 1975;Quesney et al., 1977).Recently we observed the selective metabolic activation of the mammillary bodies (MB) and their immediate connections during a threshold convulsive stimulus induced by the co-infusion of pentylenetetrazol (PTZ) and ethosuximide (ESM) (Mirski and Ferrendelli, 1983). We also reported preliminary data demonstrating that the interruption of the mamm...

Anterior Thalamic Mediation of Experimental Seizures: Selective EEG Spectral Coherence

“…Experiments supporting the hypothesis of AN mediation of convulsive activity include selective uptake of radioactively labeled glucose by AN during a threshold seizure state, as well as site-specific sensitivity to a variety of agents known to block PTZ seizure expression (12,13). Additional confirmation of the role of the AN in the expression of these seizures came from lesioning of afferent tracts synapsing on AN, and the raising of seizure threshold by localized high-frequency electrical stimulation (14,15). Such evidence has led to pilot clinical trials of AN stimulation for refractory seizures, and recently a National Institutes of Health (NIH)-sponsored clinical trial (RO1NS39344-01).…”

“…Previously we established that the thalamic anterior nuclear complex (AN), a thalamic element of the limbic system, is an important gating center for the propagation of pentylenetetrazol (PTZ) seizure activity (11)(12)(13)(14)(15). Experiments supporting the hypothesis of AN mediation of convulsive activity include selective uptake of radioactively labeled glucose by AN during a threshold seizure state, as well as site-specific sensitivity to a variety of agents known to block PTZ seizure expression (12,13).…”

Bilateral radiofrequency anterior thalamotomy in intractable epilepsy patients

“…Это привело к дальнейшему повышению ин-тереса исследователей к данной анатомической об-ласти [9]. В 1987 г. M. Mirski и J. Ferrendelli [10] опублико-вали результаты экспериментальной работы, указы-вающие на антиэпилептогенное действие электро-литического разрушения различных структур круга Пейпеца, включая форникс, мамиллоталамический тракт и мамиллярные ножки, на судорожные при-ступы у морских свинок, вызванные введением пен-тилентетразола. Локальные микроинъекции в пе-редние таламические ядра аналога γ-амино масляной кислоты мусцимола или γ-винил-γ-аминомасляной кислоты (необратимого ингибитора трансаминазы γ-аминомасляной кислоты) в исследованиях также приводили к значительному повышению резистент-ности к пентилентетразол-индуцированным судо-рогам [11,12].…”

Analysis of Gene Expression Changes in the Rat Hippocampus After Deep Brain Stimulation of the Anterior Thalamic Nucleus

“…Studies by Hamani et al, have tested the efficacy of ATN-DBS in a pilocarpine induced epilepsy model and found that bilateral ATN stimulation prolonged latencies for pilocarpine-induced seizures and status epilepticus 24 . Furthermore, high frequency stimulation of the ATN was found to reduce seizure frequency in a pentylenetetrazol (PTZ) model of epilepsy 25,[27][28][29] . Lee et al, have reported a mean reduction in seizure frequency by about 75% upon chronic deep brain stimulation of the ATN in treating refractory partial epilepsy 30 .…”