Inflammation Subverts Hippocampal Synaptic Plasticity in Experimental Multiple Sclerosis

Robert Nisticò, Dalila Mango, Georgia Mandolesi, Sonia Piccinin, Nicola Berretta, Marco Pignatelli, Marco Feligioni, Alessandra Musella, Antonietta Gentile, Francesco Mori, Giorgio Bernardi, Ferdinando Nicoletti, Nicola B. Mercuri, Diego Centonze

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE). In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP) induction was favored over long-term depression (LTD) in EAE, as shown by a significant rightward shift in the frequency-synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β) perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC) without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS.

Original languageEnglish
Article numbere54666
JournalPloS one
Volume8
Issue number1
DOIs
StatePublished - Jan 29 2013

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