RT Journal Article
SR Electronic
T1 Microglia-Dependent Alteration of Glutamatergic Synaptic Transmission and Plasticity in the Hippocampus during Peripheral Inflammation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4942
OP 4952
DO 10.1523/JNEUROSCI.4485-14.2015
VO 35
IS 12
A1 Kiarash Riazi
A1 Michael A. Galic
A1 Amanda C. Kentner
A1 Aylin Y. Reid
A1 Keith A. Sharkey
A1 Quentin J. Pittman
YR 2015
UL http://www.jneurosci.org/content/35/12/4942.abstract
AB Peripheral inflammatory diseases are often associated with behavioral comorbidities including anxiety, depression, and cognitive dysfunction, but the mechanism for these is not well understood. Changes in the neuronal and synaptic functions associated with neuroinflammation may underlie these behavioral abnormalities. We have used a model of colonic inflammation induced by 2,4,6-trinitrobenzenesulfonic acid in Sprague Dawley rats to identify inflammation-induced changes in hippocampal synaptic transmission. Hippocampal slices obtained 4 d after the induction of inflammation revealed enhanced Schaffer collateral-induced excitatory field potentials in CA1 stratum radiatum. This was associated with larger-amplitude mEPSCs, but unchanged mEPSC frequencies and paired-pulse ratios, suggesting altered postsynaptic effects. Both AMPA- and NMDA-mediated synaptic currents were enhanced, and analysis of AMPA-mediated currents revealed increased contributions of GluR2-lacking receptors. In keeping with this, both transcripts and protein levels of the GluR2 subunit were reduced in hippocampus. Both long-term potentiation (LTP) and depression (LTD) were significantly reduced in hippocampal slices taken from inflamed animals. Chronic administration of the microglial/macrophage activation inhibitor minocycline to the inflamed animals both lowered the level of the cytokine tumor necrosis factor α in the hippocampus and completely abolished the effect of peripheral inflammation on the field potentials and synaptic plasticity (LTP and LTD). Our results reveal profound synaptic changes caused by a mirror microglia-mediated inflammatory response in hippocampus during peripheral organ inflammation. These synaptic changes may underlie the behavioral comorbidities seen in patients.