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Developmental regulation of CB1-mediated spike-time dependent depression at immature mossy fiber-CA3 synapses.

Caiati MD, Sivakumaran S, Lanore F, Mulle C, Richard E, Verrier D, Marsicano G, Miles R, Cherubini E - Sci Rep (2012)

Bottom Line: Thus, STD-LTD was prevented by CB1 receptor antagonists and was absent in CB1-KO mice.Consistent with these data, in situ hybridization experiments revealed detectable level of CB1 mRNA in the granule cell layer at P3 but not at P21.These results indicate that CB1 receptors are transiently expressed on immature MF terminals where they counteract the enhanced neuronal excitability induced by the excitatory action of GABA.

View Article: PubMed Central - PubMed

ABSTRACT
Early in postnatal life, mossy fibres (MF), the axons of granule cells in the dentate gyrus, release GABA which is depolarizing and excitatory. Synaptic currents undergo spike-time dependent long-term depression (STD-LTD) regardless of the temporal order of stimulation (pre versus post and viceversa). Here we show that at P3 but not at P21, STD-LTD, induced by negative pairing, is mediated by endocannabinoids mobilized from the postsynaptic cell during spiking-induced membrane depolarization. By diffusing backward, endocannabinoids activate cannabinoid type-1 (CB1) receptors probably expressed on MF. Thus, STD-LTD was prevented by CB1 receptor antagonists and was absent in CB1-KO mice. Consistent with these data, in situ hybridization experiments revealed detectable level of CB1 mRNA in the granule cell layer at P3 but not at P21. These results indicate that CB1 receptors are transiently expressed on immature MF terminals where they counteract the enhanced neuronal excitability induced by the excitatory action of GABA.

No MeSH data available.


Related in: MedlinePlus

Lack of CB1-mediated STD-LTD in hippocampal slices obtained from P19–P25 old rats.(A) Glutamatergic MF-EPSCs evoked in the presence of picrotoxin (100 μM) before (Control), after pairing, after addition of DCG-IV or DCG-IV plus DNQX. The inset above the traces shows paired pulse facilitation of MF-EPSCs. (B) Mean amplitude of MF-EPSCs before and after pairing (arrows at time 0) versus time (n = 19). Note that pairing did not affect synaptic responses. These were strongly reduced by DCG-IV and blocked by DNQX.
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f7: Lack of CB1-mediated STD-LTD in hippocampal slices obtained from P19–P25 old rats.(A) Glutamatergic MF-EPSCs evoked in the presence of picrotoxin (100 μM) before (Control), after pairing, after addition of DCG-IV or DCG-IV plus DNQX. The inset above the traces shows paired pulse facilitation of MF-EPSCs. (B) Mean amplitude of MF-EPSCs before and after pairing (arrows at time 0) versus time (n = 19). Note that pairing did not affect synaptic responses. These were strongly reduced by DCG-IV and blocked by DNQX.

Mentions: It is well known that CB1 receptors are not expressed on juvenile glutamatergic MF terminals162122. Therefore, in the following experiments we tested whether the same pairing protocol used in neonates can induce CB1-dependent STD-LTD at MF-evoked glutamatergic excitatory postsynaptic currents (EPSCs) in CA3 principal cells of P19–P25 old animals. These experiments were routinely performed in the presence of picrotoxin (100 μM) to block GABAA receptors. Consistent with their MF origin, EPSCs were highly sensitive to group II mGluR agonist DCG-IV23. At the concentration of 4 μM this compound induced a 75.8 ± 2.1% reduction in the peak amplitude of EPSCs (Fig. 7). As shown in Fig. 7, negative pairing (post before pre) failed to modify synaptic strength in all neurons tested (n = 19; from 6 rats). After pairing the EPSCs amplitude was 104 ± 7% of controls (p = 0.84; paired t-test).


Developmental regulation of CB1-mediated spike-time dependent depression at immature mossy fiber-CA3 synapses.

Caiati MD, Sivakumaran S, Lanore F, Mulle C, Richard E, Verrier D, Marsicano G, Miles R, Cherubini E - Sci Rep (2012)

Lack of CB1-mediated STD-LTD in hippocampal slices obtained from P19–P25 old rats.(A) Glutamatergic MF-EPSCs evoked in the presence of picrotoxin (100 μM) before (Control), after pairing, after addition of DCG-IV or DCG-IV plus DNQX. The inset above the traces shows paired pulse facilitation of MF-EPSCs. (B) Mean amplitude of MF-EPSCs before and after pairing (arrows at time 0) versus time (n = 19). Note that pairing did not affect synaptic responses. These were strongly reduced by DCG-IV and blocked by DNQX.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3285903&req=5

f7: Lack of CB1-mediated STD-LTD in hippocampal slices obtained from P19–P25 old rats.(A) Glutamatergic MF-EPSCs evoked in the presence of picrotoxin (100 μM) before (Control), after pairing, after addition of DCG-IV or DCG-IV plus DNQX. The inset above the traces shows paired pulse facilitation of MF-EPSCs. (B) Mean amplitude of MF-EPSCs before and after pairing (arrows at time 0) versus time (n = 19). Note that pairing did not affect synaptic responses. These were strongly reduced by DCG-IV and blocked by DNQX.
Mentions: It is well known that CB1 receptors are not expressed on juvenile glutamatergic MF terminals162122. Therefore, in the following experiments we tested whether the same pairing protocol used in neonates can induce CB1-dependent STD-LTD at MF-evoked glutamatergic excitatory postsynaptic currents (EPSCs) in CA3 principal cells of P19–P25 old animals. These experiments were routinely performed in the presence of picrotoxin (100 μM) to block GABAA receptors. Consistent with their MF origin, EPSCs were highly sensitive to group II mGluR agonist DCG-IV23. At the concentration of 4 μM this compound induced a 75.8 ± 2.1% reduction in the peak amplitude of EPSCs (Fig. 7). As shown in Fig. 7, negative pairing (post before pre) failed to modify synaptic strength in all neurons tested (n = 19; from 6 rats). After pairing the EPSCs amplitude was 104 ± 7% of controls (p = 0.84; paired t-test).

Bottom Line: Thus, STD-LTD was prevented by CB1 receptor antagonists and was absent in CB1-KO mice.Consistent with these data, in situ hybridization experiments revealed detectable level of CB1 mRNA in the granule cell layer at P3 but not at P21.These results indicate that CB1 receptors are transiently expressed on immature MF terminals where they counteract the enhanced neuronal excitability induced by the excitatory action of GABA.

View Article: PubMed Central - PubMed

ABSTRACT
Early in postnatal life, mossy fibres (MF), the axons of granule cells in the dentate gyrus, release GABA which is depolarizing and excitatory. Synaptic currents undergo spike-time dependent long-term depression (STD-LTD) regardless of the temporal order of stimulation (pre versus post and viceversa). Here we show that at P3 but not at P21, STD-LTD, induced by negative pairing, is mediated by endocannabinoids mobilized from the postsynaptic cell during spiking-induced membrane depolarization. By diffusing backward, endocannabinoids activate cannabinoid type-1 (CB1) receptors probably expressed on MF. Thus, STD-LTD was prevented by CB1 receptor antagonists and was absent in CB1-KO mice. Consistent with these data, in situ hybridization experiments revealed detectable level of CB1 mRNA in the granule cell layer at P3 but not at P21. These results indicate that CB1 receptors are transiently expressed on immature MF terminals where they counteract the enhanced neuronal excitability induced by the excitatory action of GABA.

No MeSH data available.


Related in: MedlinePlus