THE EFFECT OF TOPIRAMATE ON EXCITATORY SYNAPTIC TRANSMISSION IN MOUSE HIPPOCAMPUS
Abstract number :
1.279
Submission category :
Year :
2002
Submission ID :
1362
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Jing Qian, Jeffrey L. Noebels. Neurology, Baylor College of Medicine, Houston, TX
RATIONALE: The present study examines the effect of the AED topiramate (TPM) on synaptic transmission at a fast excitatory synapse of immature mouse brain.
METHODS: We employed fluorescence imaging techniques to investigate whether TPM modulates presynaptic Ca2+ channel function and neurotransmitter release at the CA3-CA1 synapse in hippocampal slices prepared from 3-4 week old mouse brain. Shaffer axon collateral terminals from CA3 pyramidal cells were loaded with Ca2+-sensitive fluorescence indicators. The presynaptic Ca2+ influx ([Capre]) at those terminals was measured optically, and the amount of evoked neurotransmitter release was assessed by measuring the excitatory field synaptic potential (fEPSP) with extracellular recording electrodes.
RESULTS: Application of 100 [mu]M TPM resulted in a 13% reduction of the evoked fEPSP. Since the Ca2+ signal was generated by a population of terminals, the effect of TPM on presynaptic Ca2+ channels was quantified by measuring the fluorescent Ca2+ signal as well as the presynaptic fiber volley size. On average, 100 [mu]M TPM reduced the fluorescent Ca2+ signal by 5%. The size of the fiber volley also exhibited a 6% reduction, which would entirely account for the similar amplitude decrease in optical Ca2+ signal. Of the 13% inhibition of synaptic transmission by 100 [mu]M TPM, about 5-6% was thus due to a reduction of the excitability of axon terminals. The remainder was due to an inhibition by TPM of mechanisms downstream of the presynaptic Ca2+ entry, such as a modulation of postsynaptic glutamate receptors. Therefore, our results indicate that TPM has no significant effect on presynaptic Ca2+ channel function evoked by single stimuli at this central synapse.
CONCLUSIONS: Therefore, our results indicate that TPM has no significant effect on presynaptic Ca2+ channel function evoked by single stimuli at this central synapse.
[Supported by: NINDS 29709 and Johnson and Johnson Pharmaceutical Research and Development, LLC.]; (Disclosure: Grant - This project is supported by a research grant from Johnson and Johnson Pharmaceutical Research and Development L.L.C.)