Environment matters: synaptic properties of neurons born in the epileptic adult brain develop to reduce excitability.
Neural progenitors in the adult dentate gyrus continuously produce new functional granule cells. Here we used whole-cell patch-clamp recordings to explore whether a pathological environment influences synaptic properties of new granule cells labeled with a GFP-retroviral vector. Rats were exposed to a physiological stimulus, i.e., running, or a brain insult, i.e., status epilepticus, which gave rise to neuronal death, inflammation, and chronic seizures. Granule cells formed after these stimuli exhibited similar intrinsic membrane properties. However, the new neurons born into the pathological environment differed with respect to synaptic drive and short-term plasticity of both excitatory and inhibitory afferents. The new granule cells formed in the epileptic brain exhibited functional connectivity consistent with reduced excitability. We demonstrate a high degree of plasticity in synaptic inputs to adult-born new neurons, which could act to mitigate pathological brain function.
Jakubs
Katherine
K
Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, SE-221 84 Lund, Sweden.
Nanobashvili
Avtandil
A
Bonde
Sara
S
Ekdahl
Christine T
CT
Kokaia
Zaal
Z
Kokaia
Merab
M
Lindvall
Olle
O
D000818:Animals; D001522:Behavior, Animal; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D053331:Ectodysplasins / Q000378:metabolism; D004558:Electric Stimulation / Q000009:adverse effects; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005455:Fluorescent Antibody Technique / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D066298:In Vitro Techniques; D008297:Male; D008840:Microfilament Proteins; D009414:Nerve Growth Factors / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology* / Q000528:radiation effects; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012420:Running / Q000502:physiology; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D013226:Status Epilepticus / Q000209:etiology / Q000473:pathology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D053331:Ectodysplasins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D049452:Green Fluorescent Proteins