INTRINSIC OPTICAL SIGNALING REVEALS CHARACTERISTIC PATTERN OF PROPAGATION OF THE EPILEPTIFORM ACTIVITY WITHIN THE LYMBIC SYSTEM IN PILOCARPINE-TREATED EPILEPTIC RATS
Abstract number :
3.004
Submission category :
Year :
2002
Submission ID :
1011
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Giovanna D[ssquote]Arcangelo, Giuseppe Biagini, Margherita D[ssquote]Antuono, Daniela Merlo, Virginia Tancredi, Massimo Avoli. Dip.Neuroscienze, Universit[agrave] di Tor Vergata, Rome, Italy; Dip.Scienze Biomediche, Universit[agrave] di Modena e Reggio Em
RATIONALE: The pilocarpine-treated rat is an excellent model system for mesial temporal lobe epilepsy (MTLE). In both situations neuronal damage occurs in the CA3, dentate hilus and entorhinal cortex (EC) layer III. Moreover, axonal sprouting and synaptic rearrangement have been described in limbic structures both in pilocarpine-treated animals and in MTLE. Hence, changes in limbic neuronal network function may take place in both conditions. Here, we tested this hypothesis by using intrinsic optical signal (IOS) recordings along with histopathological scoring.
METHODS: Infrared-darkfield video-microscopy techniques were employed in submerged hippocampus-EC slices obtained from rats injected with pilocarpine 16-23 days earlier and from age-matched controls. Averaged darkfield images following electrical stimuli were taken through an infrared videocamera, digitised, stored and subtracted in real time. Slices were then stained for histopathological scoring.
RESULTS: In pilocarpine-treated rat slices (n=14), single-pulse electrical stimuli delivered in the medial EC induced changes in IOS that initiated close to the stimulation site and spread to the lateral EC and to the hippocampus. In addition, early changes in IOSs occurred in the CA1/subiculum area (which was presumably activated via the temporoammonic path). In contrast, in control rat slices (n=10) only repetitive stimulation of the EC deep layers induced appreciable IOS changes that propagated to the hippocampus, reaching the dentate gyrus and later CA3/CA1. Histological analysis showed damage in the dentate hilus of pilocarpine-treated rats, where almost all mossy cells disappeared and in CA3, where the lesion consisted of a 40-60% decrease in cell count.
CONCLUSIONS: Our findings demonstrate an increase in excitability of the limbic system in pilocarpine-treated rats as well as that circuit re-organization may switch EC outputs from the classic trisynaptic modality to the monosynaptic temporoammonic path. These changes may sustain the epileptic activity seen in vivo in pilocarpine-treated rats, and perhaps in MTLE patients.
[Supported by: Canadian Institutes of Health Research and Savoy Foundation.]