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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

Schaffer collateral-hippocampal CA1 basal responses in wt and CX3CR1GFP/GFP mice. (A) Histogram of fEPSP amplitude showing the facilitation of the fEPSP evoked by the second pulse, in wt and CX3CR1GFP/GFP mice, expressed as the ratio of the amplitude of the second response to that of the first (PPR). Error bars: ±SEM. (B) Stimulus intensity response curves (I–O) in wt and CX3CR1GFP/GFP mice. fEPSP in the CA1 area was increased in slope in an intensity-dependent manner. Inset: sample recordings at 0.3 (left) and 0.6 Volt (right) stimulation intensity in either wt (upper) or CX3CR1GFP/GFP mice (lower); scale vertical bar: 0.5 mV; scale horizontal bar: 50 ms.
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Figure 2: Schaffer collateral-hippocampal CA1 basal responses in wt and CX3CR1GFP/GFP mice. (A) Histogram of fEPSP amplitude showing the facilitation of the fEPSP evoked by the second pulse, in wt and CX3CR1GFP/GFP mice, expressed as the ratio of the amplitude of the second response to that of the first (PPR). Error bars: ±SEM. (B) Stimulus intensity response curves (I–O) in wt and CX3CR1GFP/GFP mice. fEPSP in the CA1 area was increased in slope in an intensity-dependent manner. Inset: sample recordings at 0.3 (left) and 0.6 Volt (right) stimulation intensity in either wt (upper) or CX3CR1GFP/GFP mice (lower); scale vertical bar: 0.5 mV; scale horizontal bar: 50 ms.

Mentions: To analyze if the lack of effect of EE on LTP in CX3CR1GFP/GFP mice could be due to altered responses to basal synaptic transmission, we performed studies of PPR and fEPSP I–O curves of synaptic transmission in wt and CX3CR1GFP/GFP mice. PPR, that is the ratio between the fEPSP amplitude evoked by the second stimulus over the first, represents a form of pre-synaptic short-term plasticity, whose variation is generally associated with changes in transmitter release probability (Zucker, 1989). To evaluate PPR values in wt and CX3CR1GFP/GFP mice, we stimulated Schaffer collateral pathway projections to CA1 at 50 ms intervals. As shown in Figure 2A, PPR was 1.22 ± 0.03 (15 slices/7mice) and 1.22 ± 0.04 (9 slices/5 mice), in CX3CR1GFP/GFP and wt mice, respectively. These findings indicate that the transmitter release probability at Schaffer collateral input is comparable between the two genotypes. We then investigated synaptic strength in CX3CR1GFP/GFP mice recording fEPSP I–O curves of synaptic transmission in term of slope of the evoked potentials. Sample traces of fEPSP recorded at different intensities are illustrated in Figure 2B: the I–O relationships of the fEPSP slope CA1 curves of the wt (7 slices/5 mice) were indistinguishable from those of CX3CR1GFP/GFP mice (12 slices/7 mice), indicating similar basal fEPSP responses to Schaffer collateral stimulation over a range of stimulus intensities.


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)

Schaffer collateral-hippocampal CA1 basal responses in wt and CX3CR1GFP/GFP mice. (A) Histogram of fEPSP amplitude showing the facilitation of the fEPSP evoked by the second pulse, in wt and CX3CR1GFP/GFP mice, expressed as the ratio of the amplitude of the second response to that of the first (PPR). Error bars: ±SEM. (B) Stimulus intensity response curves (I–O) in wt and CX3CR1GFP/GFP mice. fEPSP in the CA1 area was increased in slope in an intensity-dependent manner. Inset: sample recordings at 0.3 (left) and 0.6 Volt (right) stimulation intensity in either wt (upper) or CX3CR1GFP/GFP mice (lower); scale vertical bar: 0.5 mV; scale horizontal bar: 50 ms.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Schaffer collateral-hippocampal CA1 basal responses in wt and CX3CR1GFP/GFP mice. (A) Histogram of fEPSP amplitude showing the facilitation of the fEPSP evoked by the second pulse, in wt and CX3CR1GFP/GFP mice, expressed as the ratio of the amplitude of the second response to that of the first (PPR). Error bars: ±SEM. (B) Stimulus intensity response curves (I–O) in wt and CX3CR1GFP/GFP mice. fEPSP in the CA1 area was increased in slope in an intensity-dependent manner. Inset: sample recordings at 0.3 (left) and 0.6 Volt (right) stimulation intensity in either wt (upper) or CX3CR1GFP/GFP mice (lower); scale vertical bar: 0.5 mV; scale horizontal bar: 50 ms.
Mentions: To analyze if the lack of effect of EE on LTP in CX3CR1GFP/GFP mice could be due to altered responses to basal synaptic transmission, we performed studies of PPR and fEPSP I–O curves of synaptic transmission in wt and CX3CR1GFP/GFP mice. PPR, that is the ratio between the fEPSP amplitude evoked by the second stimulus over the first, represents a form of pre-synaptic short-term plasticity, whose variation is generally associated with changes in transmitter release probability (Zucker, 1989). To evaluate PPR values in wt and CX3CR1GFP/GFP mice, we stimulated Schaffer collateral pathway projections to CA1 at 50 ms intervals. As shown in Figure 2A, PPR was 1.22 ± 0.03 (15 slices/7mice) and 1.22 ± 0.04 (9 slices/5 mice), in CX3CR1GFP/GFP and wt mice, respectively. These findings indicate that the transmitter release probability at Schaffer collateral input is comparable between the two genotypes. We then investigated synaptic strength in CX3CR1GFP/GFP mice recording fEPSP I–O curves of synaptic transmission in term of slope of the evoked potentials. Sample traces of fEPSP recorded at different intensities are illustrated in Figure 2B: the I–O relationships of the fEPSP slope CA1 curves of the wt (7 slices/5 mice) were indistinguishable from those of CX3CR1GFP/GFP mice (12 slices/7 mice), indicating similar basal fEPSP responses to Schaffer collateral stimulation over a range of stimulus intensities.

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