Electrophysiological Evidence of Monosynaptic Excitatory Transmission Between Granule Cells After Seizure-Induced Mossy Fiber Sprouting

Abstract

evidence of monosynaptic excitatory transmission between granule cells after seizure-induced mossy fiber sprouting. J Neurophysiol 90: 2536 -2547, 2003; 10.1152/jn.00251.2003. Mossy fiber sprouting is a form of synaptic reorganization in the dentate gyrus that occurs in human temporal lobe epilepsy and animal models of epilepsy. The axons of dentate gyrus granule cells, called mossy fibers, develop collaterals that grow into an abnormal location, the inner third of the dentate gyrus molecular layer. Electron microscopy has shown that sprouted fibers from synapses on both spines and dendritic shafts in the inner molecular layer, which are likely to represent the dendrites of granule cells and inhibitory neurons. One of the controversies about this phenomenon is whether mossy fiber sprouting contributes to seizures by forming novel recurrent excitatory circuits among granule cells. To date, there is a great deal of indirect evidence that suggests this is the case, but there are also counterarguments. The purpose of this study was to determine whether functional monosynaptic connections exist between granule cells after mossy fiber sprouting. Using simultaneous recordings from granule cells, we obtained direct evidence that granule cells in epileptic rats have monosynaptic excitatory connections with other granule cells. Such connections were not obtained when age-matched, saline control rats were examined. The results suggest that indeed mossy fiber sprouting provides a substrate for monosynaptic recurrent excitation among granule cells in the dentate gyrus. Interestingly, the characteristics of the excitatory connections that were found indicate that the pathway is only weakly excitatory. These characteristics may contribute to the empirical observation that the sprouted dentate gyrus does not normally generate epileptiform discharges.

Input-specific plasticity at excitatory synapses mediated by endocannabinoids in the dentate gyrus

“…The axonal projections from mossy cells travel long distances and innervate many granule cells (Buckmaster et al, 1996;Scharfman et al, 2003). Consequently, hilar mossy cells have been thought to mediate the coordination and integration of neuronal activity from different populations of DGCs along the septotemporal axis (Amaral and Witter, 1989).…”

The adenosine kinase hypothesis of epileptogenesis

“…However, seizure-induced plasticity shows a different pattern of reorganization in the immature brain (Cross and Cavazos, 2007). In adult brain, sprouting mossy fibers grow aberrant collaterals into the inner molecular layer of the dentate gyrus, where they preferentially make synaptic contacts with dendrites of other granule neurons, leading to the formation of excitatory feedback circuits (Buckmaster et al, 2002;Scharfman et al, 2003).…”

Kainic acid‐induced recurrent mossy fiber innervation of dentate gyrus inhibitory interneurons: Possible anatomical substrate of granule cell hyperinhibition in chronically epileptic rats

“…Unlike granule cells, dentate inhibitory interneurons normally receive granule cell input (Ribak and Peterson, 1991;Blasco-Ibanez et al, 2000;Seress et al, 2001), and can therefore be assumed to possess all of the components of the intracellular signaling pathways that mediate normal interneuron-granule cell influences. The possibility that granule cells constitutively lack the cellular apparatus to respond fully to abnormal input from other granule cells might underlie the observation that direct interactions among granule cells are relatively weak in the synaptically reorganized dentate gyrus (Scharfman et al, 2003), although this is clearly conjectural.…”