Abstracts

In temporal lobe epilepsy granule cells develop aberrant positive-feedback circuits through basal dendrites in the hilus and through sprouted axons that synapse with dendrites in the molecular layer. Previous studies provide data on the proportion of granule cells with axon projections into the molecular layer, sprouted axon lengths, synapse density and targets, and the proportion of granule cells with basal dendrites in models of temporal lobe epilepsy. However, the extent of recurrent excitation through molecular layer axon projections versus basal dendrites is unclear. Cells were intracellularly labeled with biocytin in epileptic pilocarpine-treated rats. To evaluate basal dendrite length, granule cells (n=15), each with one basal dendrite, were labeled in hippocampal slice experiments. To evaluate synapse density, an additional granule cell with a basal dendrite was labeled in vivo, the tissue was processed for post-embedding GABA-immunoreactivity, and a 182-[mu]m-long segment of the basal dendrite was reconstructed from serial electron micrographs. Putative synapses were identified by parallel membranes and the presynaptic concentration of synaptic vesicles. Average basal dendrite length per granule cell was 551 [plusmn] 129 [mu]m (mean [plusmn] sem), which accounted for 15 [plusmn] 4% of the cell[apos]s total dendritic length. The reconstructed basal dendrite segment received 0.25 GABA-positive synapses/[mu]m and 4.5 GABA-negative synapses/[mu]m for a total of 865 putative synapses. A surprisingly high proportion (39%) of the GABA-negative synapses were with the shaft. Integrating light microscopic data on basal dendrite length with EM data on synapse density, we estimate that an average basal dendrite receives 140 inhibitory and 2500 excitatory synapses. Previous studies found that in epileptic rats [sim]14% of granule cells develop basal dendrites, [sim]60% develop axon projections into the molecular layer, and the average granule cell with molecular layer projections forms [sim]500 new synapses with other granule cells. From these data we estimate that the probability of monosynaptic excitation among granule cells is 1% through axon projections into the molecular layer and up to an additional 1.3% through basal dendrites. Basal dendrites primarily receive excitatory synaptic input and could contribute substantially to recurrent excitation. Basal dendrite development and axon sprouting into the molecular layer convert the granule cell network from one with virtually no monosynaptic connections to one with interconnectivity approaching that found in the CA3 field. Therefore, to successfully prevent the development of recurrent, excitatory, synaptic reorganization after epileptogenic injuries it will be necessary to block both axon sprouting into the molecular layer and synaptogenesis with granule cell basal dendrites. (Supported by NIH/NINDS.)