Limbic Network Interactions Leading to Hyperexcitability in Temporal Lobe Epilepsy.
Abstract number :
1.017
Submission category :
Year :
2001
Submission ID :
2306
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
V. Tancredi, MD, Neuroscience, University of Rome [dsquote]Tor Vergata[dsquote], Rome, Italy; G. D[ssquote]Arcangelo, MD, Neuroscience, University of Rome [dsquote]Tor Vergata[dsquote], Rome, Italy; M. D[ssquote]Antuono, PhD, Neurology and Neurosurgery, a
RATIONALE: In rodent brain slices containing reciprocally connected hippocampus and entorhinal cortex (EC) networks, CA3 outputs con-trol the EC propensity to generate ictal-like discharges resembling electrographic seizures. Neuronal damage in limbic areas such as CA3 and dentate hilus, occurs in temporal lobe epilepsy both in humans and in animal models. Hence, hippocampal damage may lead to decreased CA3 output function that in turn would allow EC networks to generate seizures. Here we tested this hypothesis by using conventional electrophysiological recondings along with intrinsic optical signal (IOS) recordings.
METHODS: Combined hippocampus-EC slices were obtained from either mice or rats that were injected with pilocarpine (i.p.) 13-22 days before obtaining slices. Age-matched animals were used as control. Field potential recordings were made with NaCl-filled electrodes while averaged darkfield images following focal electrical stimuli were captured with an infrared videocamera, digitised, stored and then subtracted in real time. Elpileptiform activity was induced by 4-aminopyridine (4AP, 50[mu]m)
RESULTS: CA3-driven interictal discharges induced by 4AP in hippocampus-EC slices from rats or mice injected with pilocarpine had a lower frequency than in age-matched control slices. Moreover, EC-driven ictal-like discharges in pilocarpine-treated slices occurred throughout the experiment (up to 6h) and spread to the CA1/subicular area via the temporoammonic path; in contrast, they disappeared in control slices within 2h of 4AP application and propagated via the trisynaptic hippocampal circuit. IOS analysis revealed that the spread of excitation in pilocarpine-treated slices was more pronounced in the CA1 and reduced in the CA3 when compared with control slices.
CONCLUSIONS: Different network interactions within the hippocampus-EC loop characterize control and pilocarpine-treated slices maintained in vitro. These functional changes, which are presumably caused by seizure-induced cell damage, may lead to seizures in vivo. This process is facilitated by a decreased control of EC excitability by hippocampal outputs and sustained by the reverberant activity between EC and CA1/subiculum networks that are excited via the temporoammonic path.
Support: CIHR
Disclosure: Grant - CIHR