Activity deprivation leads to seizures in hippocampal slice cultures: is epilepsy the consequence of homeostatic plasticity?
Neural networks operate robustly despite destabilizing factors, ranging from gene product turnover to circuit refinement, throughout life. Maintaining functional robustness of neuronal networks critically depends upon forms of homeostatic plasticity including synaptic scaling. Synaptic strength and intrinsic excitability have been shown to "scale" (up or down) in response to altered ambient activity levels, and this has led to the general idea that homeostatic plasticity operates along a continuum. After 48 hours of activity deprivation, cultured hippocampal networks exhibited a homeostatic-type reconfiguration that was discrete: a switch from spontaneous spiking to oscillatory bursting. Blockade of fast glutamatergic and GABAergic transmission abolished spontaneous network bursting, but the majority of neurons exhibited intrinsic bursting in response to current injection, which was not the case in control tissue. This de novo intrinsic bursting could be blocked by cadmium chloride, suggesting that this bursting involves calcium mechanisms. Immunohistochemistry confirmed that activity-deprived slice cultures exhibited a widespread upregulation of voltage-dependent calcium channels compared with controls. Calcium imaging studies from activity-deprived slices demonstrated that spontaneous bursting was not a local behavior, but rather a global, synchronous phenomenon, reminiscent of seizure activity. These data suggest that the input/output transformation of individual neurons undergoing homeostatic remodeling is more complex than simple scaling. Network consequences of this transformation include network destabilization of epileptic proportions. Spontaneous activity plays a critical role in actively maintaining homeostatic balance in networks, which is lost after activity deprivation.
Trasande
Caitlin Aptowicz
CA
Committee on Neurobiology, Department of Organismal Biology and Anatomy, The University of Chicago, Chicago, Illinois, USA. Jramire@uchicago.edu
Ramirez
Jan-Marino
JM
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D012640:Seizures / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D013779:Tetrodotoxin; D002118:Calcium