Surviving hilar somatostatin interneurons enlarge, sprout axons, and form new synapses with granule cells in a mouse model of temporal lobe epilepsy.
In temporal lobe epilepsy, seizures initiate in or near the hippocampus, which frequently displays loss of neurons, including inhibitory interneurons. It is unclear whether surviving interneurons function normally, are impaired, or develop compensatory mechanisms. We evaluated GABAergic interneurons in the hilus of the dentate gyrus of epileptic pilocarpine-treated GIN mice, specifically a subpopulation of somatostatin interneurons that expresses enhanced green fluorescence protein (GFP). GFP-immunocytochemistry and stereological analyses revealed substantial loss of GFP-positive hilar neurons (GPHNs) but increased GFP-positive axon length per dentate gyrus in epileptic mice. Individual biocytin-labeled GPHNs in hippocampal slices from epileptic mice also had larger somata, more axon in the molecular layer, and longer dendrites than controls. Dual whole-cell patch recording was used to test for monosynaptic connections from hilar GPHNs to granule cells. Unitary IPSCs (uIPSCs) recorded in control and epileptic mice had similar average rise times, amplitudes, charge transfers, and decay times. However, the probability of finding monosynaptically connected pairs and evoking uIPSCs was 2.6 times higher in epileptic mice compared to controls. Together, these findings suggest that surviving hilar somatostatin interneurons enlarge, extend dendrites, sprout axon collaterals in the molecular layer, and form new synapses with granule cells. These epilepsy-related changes in cellular morphology and connectivity may be mechanisms for surviving hilar interneurons to inhibit more granule cells and compensate for the loss of vulnerable interneurons.
Zhang
Wei
W
Department of Comparative Medicine, Stanford University, Stanford, California 94305, USA.
Yamawaki
Ruth
R
Wen
Xiling
X
Uhl
Justin
J
Diaz
Jessica
J
Prince
David A
DA
Buckmaster
Paul S
PS
D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology; D048429:Cell Size; D002470:Cell Survival; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials; D007395:Interneurons / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D010862:Pilocarpine; D013004:Somatostatin / Q000378:metabolism*; D013569:Synapses / Q000473:pathology / Q000502:physiology
D010862:Pilocarpine; D049452:Green Fluorescent Proteins; D013004:Somatostatin