title: Tumour necrosis factor-mediated homeostatic synaptic plasticity in behavioural models: testing a role in maternal immune activation.
abstract: The proinflammatory cytokine tumour necrosis factor-alpha (TNFα) has long been characterized for its role in the innate immune system, but more recently has been found to have a distinct role in the nervous system that does not overlap with other proinflammatory cytokines. Through regulation of neuronal glutamate and GABA receptor trafficking, TNF mediates a homeostatic form of synaptic plasticity, but plays no direct role in Hebbian forms of plasticity. As yet, there is no evidence to suggest that this adaptive plasticity plays a significant role in normal development, but it does maintain neuronal circuit function in the face of several types of disruption. This includes developmental plasticity in primary sensory cortices, as well as modulating the response to antidepressants, chronic antipsychotics and drugs of abuse. TNF is also a prominent component of the neuroinflammation occurring in most neuropathologies, but the role of TNF-mediated synaptic plasticity in this context remains to be determined. We tested this in a maternal immune activation (MIA) model of neurodevelopmental disorders. Using TNF-/-mice, we observed that TNF is not required for the expression of abnormal social or anxious behaviour in this model. This indicates that TNF does not uniquely contribute to the development of neuronal dysfunction in this model, and suggests that during neuroinflammatory events, compensation between the various proinflammatory cytokines is the norm.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'.
authors.affiliation: Department of Neurology and Neurosurgery, Centre for Research in Neuroscience, The Research Institute of the McGill University Health Center, Montreal, Quebec, Canada H3G 1A4.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Konefal
authors.affiliation: Department of Neurology and Neurosurgery, Centre for Research in Neuroscience, The Research Institute of the McGill University Health Center, Montreal, Quebec, Canada H3G 1A4 david.stellwagen@mcgill.ca.
authors.forename: David
authors.identifier: 0000-0003-3509-103X
authors.initials: D
authors.lastname: Stellwagen
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics*; D006706:Homeostasis; D008297:Male; D000072741:Maternal Inheritance; D051379:Mice; D065886:Neurodevelopmental Disorders / Q000235:genetics*; D009473:Neuronal Plasticity; D012919:Social Behavior; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: cytokine; homeostatic plasticity; inflammation; maternal immune activation