Abstract
In recent years several evidence demonstrated that some features of hippocampal biology, like neurogenesis, synaptic transmission, learning, and memory performances are deeply modulated by social, motor, and sensorial experiences. Fractalkine/CX3CL1 is a transmembrane chemokine abundantly expressed in the brain by neurons, where it modulates glutamatergic transmission and long-term plasticity processes regulating the intercellular communication between glia and neurons, being its specific receptor CX3CR1 expressed by microglia. In this paper we investigated the role of CX3CL1/CX3CR1 signaling on experience-dependent hippocampal plasticity processes. At this aim wt and CX3CR1GFP/GFP mice were exposed to long-lasting-enriched environment (EE) and the effects on hippocampal functions were studied by electrophysiological recordings of long-term potentiation of synaptic activity, behavioral tests of learning and memory in the Morris water maze paradigm and analysis of neurogenesis in the subgranular zone of the dentate gyrus (DG). We found that CX3CR1 deficiency increases hippocampal plasticity and spatial memory, blunting the potentiating effects of EE. In contrast, exposure to EE increased the number and migration of neural progenitors in the DG of both wt and CX3CR1GFP/GFP mice. These data indicate that CX3CL1/CX3CR1-mediated signaling is crucial for a normal experience-dependent modulation of hippocampal functions.
Highlights
The importance of the environment in the regulation of brain physiology and behavior has long been recognized in biological, social, and medical science
The post hoc analysis revealed that (i) the fEPSP potentiation was significantly higher in CX3CR1GFP/green fluorescent protein (GFP) standard environment (SE) compared to wt SE (p = 0.042), indicating that in control conditions CX3CR1GFP/GFP mice showed an enhanced plasticity, confirmed in littermates (Figure A1 in Appendix); (ii) the wt EE showed a significant enhancement compared to wt SE (p < 0.001), indicating that EE affects only wt mice
In order to assess the role of CX3CL1/CX3CR1 signaling on learning and memory abilities, we investigated the effects of 2.5 months exposure to either SE or EE on wt and CX3CR1GFP/GFP mice in the Morris water maze test
Summary
The importance of the environment in the regulation of brain physiology and behavior has long been recognized in biological, social, and medical science. Hippocampal slices from the brain of “enriched” mice show enhanced LTP in the Schaffer collateral pathway of area CA1 (Duffy et al, 2001), suggesting that exposure to EE may modify synaptic physiology in hippocampal neurons (Foster et al, 1996; van Praag et al, 1999). The factors mediating the effect of enrichment on behavior have been only partially identified Among these factors, cytokines appear to exert an important function (Goshen et al, 2009) the role of CHEMOtactic cytoKINES (chemokines) has not been explored, yet. Chemokines contribute to cell-to-cell communication (Tran and Miller, 2003), modulating neurotransmitter release and plasticity
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