Abstract
We report on a novel mouse in vitro brain slice preparation that contains intact callosal axons connecting anterior cingulate cortices (ACC). Callosal connections are demonstrated by the ability to regularly record epileptiform events between hemispheres (bilateral events). That the correlation of these events depends on the callosum is demonstrated by the bisection of the callosum in vitro. Epileptiform events are evoked with four different methods: (1) bath application of bicuculline (a GABA-A antagonist); (2) bicuculline+MK801 (an NMDA receptor antagonist), (3) a zero magnesium extracellular solution (0Mg); (4) focal application of bicuculline to a single cortical hemisphere. Significant increases in the number of epileptiform events, as well as increases in the ratio of bilateral events to unilateral events, are observed during bath applications of bicuculline, but not during applications of bicuculline+MK-801. Long ictal-like events (defined as events >20 seconds) are only observed in 0Mg. Whole cell patch clamp recordings of single neurons reveal strong feedforward inhibition during focal epileptiform events in the contralateral hemisphere. Within the ACC, we find differences between the rostral areas of ACC vs. caudal ACC in terms of connectivity between hemispheres, with the caudal regions demonstrating shorter interhemispheric latencies. The morphologies of many patch clamped neurons show callosally-spanning axons, again demonstrating intact callosal circuits in this in vitro preparation.
Highlights
The corpus callosum is the largest white matter tract connecting the two hemispheres in eutherians, and ablation of the anterior corpus callosum can be an effective treatment for otherwise intractable epilepsy in humans [1,2,3]
Results from the 0Mg model differed significantly from the bicuculline model (BIC) model in other measures: (1) EEs were smaller in amplitudes (Table 1, Fig. 4Ai and Bi); (2) in 10 out of the 27 0Mg slices that produced any EEs, there were the developments of ictal-like events, in sharp contrast to the BIC recordings where the longest EEs had durations of 2 seconds (Fig. 4Aii vs 4Bii); (3) 0Mg slices with bilateral EEs showed higher proportions of unilateral EEs compared to BIC slices
Borrowing terminology introduced for rat cingulate cortex, it is likely that slice 4 belongs to mid-cingulate cortex (MCC), while slices 1 and 2 belong to perigenual anterior cingulate cortices (ACC) [22]
Summary
The corpus callosum is the largest white matter tract connecting the two hemispheres in eutherians, and ablation of the anterior corpus callosum (callosotomy) can be an effective treatment for otherwise intractable epilepsy in humans [1,2,3]. In non-humans, it has been shown that bilateral synchrony of the cortical hemispheres during epileptic seizures depends on the callosum [4,5,6,7] These studies suggest that the callosal circuits serve as routes for seizure generalization. We have developed a mouse in vitro slice preparation from anterior cingulate cortex that demonstrates the coordination of seizures in both hemispheres via the callosum. An advantage of this preparation includes the finding that bilateral seizures are mediated only through the callosum and not through other commissures or thalamic routes, allowing a preparation that focuses solely on the role of callosal circuits in communication between the two hemispheres. This seizure bilateralization can be studied with control of the extracellular environment and with cellular resolution
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