Article

Initial loss but later excess of GABAergic synapses with dentate granule cells in a rat model of temporal lobe epilepsy. J Comp Neurol

Department of Comparative Medicine, Stanford University, California 94305, USA.
The Journal of Comparative Neurology (Impact Factor: 3.23). 03/2010; 518(5):647-67. DOI: 10.1002/cne.22235
Source: PubMed

ABSTRACT

Many patients with temporal lobe epilepsy display neuron loss in the dentate gyrus. One potential epileptogenic mechanism is loss of GABAergic interneurons and inhibitory synapses with granule cells. Stereological techniques were used to estimate numbers of gephyrin-positive punctae in the dentate gyrus, which were reduced short-term (5 days after pilocarpine-induced status epilepticus) but later rebounded beyond controls in epileptic rats. Stereological techniques were used to estimate numbers of synapses in electron micrographs of serial sections processed for postembedding GABA-immunoreactivity. Adjacent sections were used to estimate numbers of granule cells and glutamic acid decarboxylase-positive neurons per dentate gyrus. GABAergic neurons were reduced to 70% of control levels short-term, where they remained in epileptic rats. Integrating synapse and cell counts yielded average numbers of GABAergic synapses per granule cell, which decreased short-term and rebounded in epileptic animals beyond control levels. Axo-shaft and axo-spinous GABAergic synapse numbers in the outer molecular layer changed most. These findings suggest interneuron loss initially reduces numbers of GABAergic synapses with granule cells, but later, synaptogenesis by surviving interneurons overshoots control levels. In contrast, the average number of excitatory synapses per granule cell decreased short-term but recovered only toward control levels, although in epileptic rats excitatory synapses in the inner molecular layer were larger than in controls. These findings reveal a relative excess of GABAergic synapses and suggest that reports of reduced functional inhibitory synaptic input to granule cells in epilepsy might be attributable not to fewer but instead to abundant but dysfunctional GABAergic synapses.

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Available from: Ruth Yamawaki, Apr 01, 2015
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    • "Elavl4 has been shown to be expressed in interneurons in the hippocampus (Bolognani et al., 2004), and it has been shown to be involved in transporting mRNA in neuronal processes, leading to neurite outgrowth and changes in neuroplasticity (Aronov et al., 2002; Bolognani et al., 2007; Tanner et al., 2008). These processes could underlie several alterations in inhibitory interneurons or dentate granule neurons that have been observed in the epileptic brain, including increased axonal growth and synaptogenesis (Dudek and Sutula, 2007; Thind et al., 2010). In addition, properties of synaptic vesicle release probabilities have been shown to be altered in interneurons and mossy fibers in epileptic animals (Goussakov et al., 2000; Kobayashi and Buckmaster, 2003). "
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