Axonal sprouting of excitatory neurons is frequently observed in temporal lobe 
epilepsy, but the extent to which inhibitory interneurons undergo similar axonal 
reorganization remains unclear. The goal of this study was to determine whether 
somatostatin (SOM)-expressing neurons in stratum (s.) oriens of the hippocampus 
exhibit axonal sprouting beyond their normal territory and innervate granule 
cells of the dentate gyrus in a pilocarpine model of epilepsy. To obtain 
selective labeling of SOM-expressing neurons in s. oriens, a Cre 
recombinase-dependent construct for channelrhodopsin2 fused to enhanced yellow 
fluorescent protein (ChR2-eYFP) was virally delivered to this region in SOM-Cre 
mice. In control mice, labeled axons were restricted primarily to s. 
lacunosum-moleculare. However, in pilocarpine-treated animals, a rich plexus of 
ChR2-eYFP-labeled fibers and boutons extended into the dentate molecular layer. 
Electron microscopy with immunogold labeling demonstrated labeled axon terminals 
that formed symmetric synapses on dendritic profiles in this region, consistent 
with innervation of granule cells. Patterned illumination of ChR2-labeled fibers 
in s. lacunosum-moleculare of CA1 and the dentate molecular layer elicited 
GABAergic inhibitory responses in dentate granule cells in pilocarpine-treated 
mice but not in controls. Similar optical stimulation in the dentate hilus 
evoked no significant responses in granule cells of either group of mice. These 
findings indicate that under pathological conditions, SOM/GABAergic neurons can 
undergo substantial axonal reorganization beyond their normal territory and 
establish aberrant synaptic connections. Such reorganized circuitry could 
contribute to functional deficits in inhibition in epilepsy, despite the 
presence of numerous GABAergic terminals in the region.