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CX(3)CR1 deficiency alters hippocampal-dependent plasticity phenomena blunting the effects of enriched environment.

Maggi L, Scianni M, Branchi I, D'Andrea I, Lauro C, Limatola C - Front Cell Neurosci (2011)

Bottom Line: At this aim wt and CX(3)CR1(GFP/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 CX(3)CR1 deficiency increases hippocampal plasticity and spatial memory, blunting the potentiating effects of EE.These data indicate that CX(3)CL1/CX(3)CR1-mediated signaling is crucial for a normal experience-dependent modulation of hippocampal functions.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Università di Roma Rome Italy.

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/CX(3)CL1 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 CX(3)CR1 expressed by microglia. In this paper we investigated the role of CX(3)CL1/CX(3)CR1 signaling on experience-dependent hippocampal plasticity processes. At this aim wt and CX(3)CR1(GFP/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 CX(3)CR1 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 CX(3)CR1(GFP/GFP) mice. These data indicate that CX(3)CL1/CX(3)CR1-mediated signaling is crucial for a normal experience-dependent modulation of hippocampal functions.

No MeSH data available.


Related in: MedlinePlus

LTP in littermates wt, CX3CR1GFP/GFP and CX3CR1+/GFP mice. Points represent mean ± SEM. Of fEPSP slopes. Arrows indicate time of application of HFS. Note that after HFS, CX3CR1GFP/GFP mice (open circle) developed a robust LTP of fEPSP slope (45 min after induction: 1.34 ± 0.28 respect to baseline, 8 slices/3 mice), whereas wt mice displayed no LTP (dark circle, 1.04 ± 0.07, 6 slices/2 mice, p < 0.05 to CX3CR1GFP/GFP) and heterozygotes (open square, 1.22 ± 0.19, 6 slices/2 mice) an intermediate phenotype, respectively.
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FA1: LTP in littermates wt, CX3CR1GFP/GFP and CX3CR1+/GFP mice. Points represent mean ± SEM. Of fEPSP slopes. Arrows indicate time of application of HFS. Note that after HFS, CX3CR1GFP/GFP mice (open circle) developed a robust LTP of fEPSP slope (45 min after induction: 1.34 ± 0.28 respect to baseline, 8 slices/3 mice), whereas wt mice displayed no LTP (dark circle, 1.04 ± 0.07, 6 slices/2 mice, p < 0.05 to CX3CR1GFP/GFP) and heterozygotes (open square, 1.22 ± 0.19, 6 slices/2 mice) an intermediate phenotype, respectively.

Mentions: At the beginning of each recording, a concentric bipolar stimulating electrode (SNE-100 × 50 mm long Elektronik–Harvard Apparatus GmbH) was positioned in the stratum radiatum for stimulation of Schaffer collateral pathway projections to CA1. An ACSF-filled glass micropipette (0.5–1 MΩ) was positioned 200–600 μm from the stimulating electrode for recording orthodromically evoked fEPSPs. Stimuli consisted of 100 μs constant current square pulses, applied at 0.05 Hz. The intensity of the stimulus was adjusted in each experiment to evoke ∼50% of the maximal field potential amplitude without appreciable population spike contamination. Evoked responses were monitored online and stable baseline responses were recorded for at least 10 min. Only the slices that showed stable fEPSP amplitudes were included in the experiments. To analyze the time course of fEPSP slope, the recorded fEPSP was routinely averaged over 1 min (n = 3). LTP experiments were performed in ACSF and the averaged fEPSP (35–45 min post-induction) was normalized to the baseline values (0–10 min) before LTP induction (HFS, 1 train, 100 Hz, 1-s duration, test strength). LTP experiments in SE were replicated in CX3CR1GFP/GFP, wt and CX3CR1GFP/+ littermates (Figure A1 in Appendix).


CX(3)CR1 deficiency alters hippocampal-dependent plasticity phenomena blunting the effects of enriched environment.

Maggi L, Scianni M, Branchi I, D'Andrea I, Lauro C, Limatola C - Front Cell Neurosci (2011)

LTP in littermates wt, CX3CR1GFP/GFP and CX3CR1+/GFP mice. Points represent mean ± SEM. Of fEPSP slopes. Arrows indicate time of application of HFS. Note that after HFS, CX3CR1GFP/GFP mice (open circle) developed a robust LTP of fEPSP slope (45 min after induction: 1.34 ± 0.28 respect to baseline, 8 slices/3 mice), whereas wt mice displayed no LTP (dark circle, 1.04 ± 0.07, 6 slices/2 mice, p < 0.05 to CX3CR1GFP/GFP) and heterozygotes (open square, 1.22 ± 0.19, 6 slices/2 mice) an intermediate phenotype, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198035&req=5

FA1: LTP in littermates wt, CX3CR1GFP/GFP and CX3CR1+/GFP mice. Points represent mean ± SEM. Of fEPSP slopes. Arrows indicate time of application of HFS. Note that after HFS, CX3CR1GFP/GFP mice (open circle) developed a robust LTP of fEPSP slope (45 min after induction: 1.34 ± 0.28 respect to baseline, 8 slices/3 mice), whereas wt mice displayed no LTP (dark circle, 1.04 ± 0.07, 6 slices/2 mice, p < 0.05 to CX3CR1GFP/GFP) and heterozygotes (open square, 1.22 ± 0.19, 6 slices/2 mice) an intermediate phenotype, respectively.
Mentions: At the beginning of each recording, a concentric bipolar stimulating electrode (SNE-100 × 50 mm long Elektronik–Harvard Apparatus GmbH) was positioned in the stratum radiatum for stimulation of Schaffer collateral pathway projections to CA1. An ACSF-filled glass micropipette (0.5–1 MΩ) was positioned 200–600 μm from the stimulating electrode for recording orthodromically evoked fEPSPs. Stimuli consisted of 100 μs constant current square pulses, applied at 0.05 Hz. The intensity of the stimulus was adjusted in each experiment to evoke ∼50% of the maximal field potential amplitude without appreciable population spike contamination. Evoked responses were monitored online and stable baseline responses were recorded for at least 10 min. Only the slices that showed stable fEPSP amplitudes were included in the experiments. To analyze the time course of fEPSP slope, the recorded fEPSP was routinely averaged over 1 min (n = 3). LTP experiments were performed in ACSF and the averaged fEPSP (35–45 min post-induction) was normalized to the baseline values (0–10 min) before LTP induction (HFS, 1 train, 100 Hz, 1-s duration, test strength). LTP experiments in SE were replicated in CX3CR1GFP/GFP, wt and CX3CR1GFP/+ littermates (Figure A1 in Appendix).

Bottom Line: At this aim wt and CX(3)CR1(GFP/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 CX(3)CR1 deficiency increases hippocampal plasticity and spatial memory, blunting the potentiating effects of EE.These data indicate that CX(3)CL1/CX(3)CR1-mediated signaling is crucial for a normal experience-dependent modulation of hippocampal functions.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Università di Roma Rome Italy.

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/CX(3)CL1 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 CX(3)CR1 expressed by microglia. In this paper we investigated the role of CX(3)CL1/CX(3)CR1 signaling on experience-dependent hippocampal plasticity processes. At this aim wt and CX(3)CR1(GFP/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 CX(3)CR1 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 CX(3)CR1(GFP/GFP) mice. These data indicate that CX(3)CL1/CX(3)CR1-mediated signaling is crucial for a normal experience-dependent modulation of hippocampal functions.

No MeSH data available.


Related in: MedlinePlus