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Inhibitory Plasticity Permits the Recruitment of CA2 Pyramidal Neurons by CA3(1,2,3).

Nasrallah K, Piskorowski RA, Chevaleyre V - eNeuro (2015)

Bottom Line: We provide evidence that this effect is mediated by a long-term depression at inhibitory synapses (iLTD), as it is evoked by the same protocols and shares the same pharmacology.The disinhibitory increase in excitatory drive is sufficient to allow CA3 inputs to evoke action potential firing in CA2 PNs.Thus, these data reveal that the output of CA2 PNs can be gated by the unique activity-dependent plasticity of inhibitory neurons in area CA2.

View Article: PubMed Central - HTML - PubMed

Affiliation: Team Synaptic Plasticity and Neural Networks, FR3636, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8118, Université Paris Descartes , Sorbonne Paris Cité, 75006 Paris, France.

ABSTRACT
Area CA2 is emerging as an important region for hippocampal memory formation. However, how CA2 pyramidal neurons (PNs) are engaged by intrahippocampal inputs remains unclear. Excitatory transmission between CA3 and CA2 is strongly inhibited and is not plastic. We show in mice that different patterns of activity can in fact increase the excitatory drive between CA3 and CA2. We provide evidence that this effect is mediated by a long-term depression at inhibitory synapses (iLTD), as it is evoked by the same protocols and shares the same pharmacology. In addition, we show that the net excitatory drive of distal inputs is also increased after iLTD induction. The disinhibitory increase in excitatory drive is sufficient to allow CA3 inputs to evoke action potential firing in CA2 PNs. Thus, these data reveal that the output of CA2 PNs can be gated by the unique activity-dependent plasticity of inhibitory neurons in area CA2.

No MeSH data available.


Related in: MedlinePlus

HFS induces a long-term increase of the PSP amplitude in CA2 via a disinhibition mechanism. A, Two representative examples of the normalized PSP time course from CA2 PN whole-cell recordings illustrating how an HFS partially occludes the effect of GABAA and GABAB receptor blocker application on PSP amplitude. Top right, PSP traces corresponding to the time points before (a), after HFS (b), and after the application of GABA receptor blockers (c) with or without HFS. Bottom right, Summary histograms showing the percentage increase in the PSP amplitude induced by HFS applied alone (1), GABA receptor blocker application after HFS (2), HFS plus GABA blockers (1 + 2), and GABA blockers applied without previous HFS (3). B, Normalized CA2 PN SC PSPs recorded with either 7 mm (open circles) or 16 mm (closed circles) [Cl−] in the pipette solution. An HFS (arrow at time 0) fails to induce a long-lasting increase in PSP amplitude when a high concentration of chloride is used in the pipette solution (filled circled, p = 0.4103, n = 5) but evokes normal long-term potentiation in control experiments (open circles, p = 0.0047, n = 5). C, Summary graph of experiments performed using the gramicidin-perforated patch-recording configuration. HFS triggers an increase in PSP amplitude (p = 0.008, n = 5) similar to the one observed using whole-cell recording configuration.
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Figure 3: HFS induces a long-term increase of the PSP amplitude in CA2 via a disinhibition mechanism. A, Two representative examples of the normalized PSP time course from CA2 PN whole-cell recordings illustrating how an HFS partially occludes the effect of GABAA and GABAB receptor blocker application on PSP amplitude. Top right, PSP traces corresponding to the time points before (a), after HFS (b), and after the application of GABA receptor blockers (c) with or without HFS. Bottom right, Summary histograms showing the percentage increase in the PSP amplitude induced by HFS applied alone (1), GABA receptor blocker application after HFS (2), HFS plus GABA blockers (1 + 2), and GABA blockers applied without previous HFS (3). B, Normalized CA2 PN SC PSPs recorded with either 7 mm (open circles) or 16 mm (closed circles) [Cl−] in the pipette solution. An HFS (arrow at time 0) fails to induce a long-lasting increase in PSP amplitude when a high concentration of chloride is used in the pipette solution (filled circled, p = 0.4103, n = 5) but evokes normal long-term potentiation in control experiments (open circles, p = 0.0047, n = 5). C, Summary graph of experiments performed using the gramicidin-perforated patch-recording configuration. HFS triggers an increase in PSP amplitude (p = 0.008, n = 5) similar to the one observed using whole-cell recording configuration.

Mentions: If the increase in the PSP after HFS indeed results from a decrease in inhibition, then it is possible to make the following prediction: pharmacological block of inhibition should increase the amplitude of the PSP, and part of this increase should be occluded by a previous HFS. In order to test this, we performed current-clamp recordings of CA2 PNs and applied GABA receptor blockers after an HFS of SC inputs, or in control experiments with no tetanus stimulation. We found that when the GABA receptor blockers were applied without the HFS, the PSP amplitude was strongly increased (Fig. 3A; 472.8 ± 85.5% of the PSP amplitude, p = 0.0026, n = 6), confirming that GABAergic transmission exerts a strong negative control on the PSP amplitude in CA2 PNs (Piskorowski and Chevaleyre, 2013). When the GABA receptor blockers were applied after the HFS, the increase in the PSP amplitude was smaller than the effect of the blockers applied without the HFS [Fig. 3A; 185.8 ± 7.8% of increase of the PSP amplitude, p < 0.00001 (p = 0.0074 compared with blockers without HFS), n = 6]. However, the final PSP amplitude after the HFS and GABA blocker application was identical to the amplitude of the PSP after GABA blocker application alone (Fig. 3A; p = 0.7, n = 6). Altogether, these results indicate that the HFS-induced increase of the PSP amplitude is mediated by a decrease in GABAergic transmission.


Inhibitory Plasticity Permits the Recruitment of CA2 Pyramidal Neurons by CA3(1,2,3).

Nasrallah K, Piskorowski RA, Chevaleyre V - eNeuro (2015)

HFS induces a long-term increase of the PSP amplitude in CA2 via a disinhibition mechanism. A, Two representative examples of the normalized PSP time course from CA2 PN whole-cell recordings illustrating how an HFS partially occludes the effect of GABAA and GABAB receptor blocker application on PSP amplitude. Top right, PSP traces corresponding to the time points before (a), after HFS (b), and after the application of GABA receptor blockers (c) with or without HFS. Bottom right, Summary histograms showing the percentage increase in the PSP amplitude induced by HFS applied alone (1), GABA receptor blocker application after HFS (2), HFS plus GABA blockers (1 + 2), and GABA blockers applied without previous HFS (3). B, Normalized CA2 PN SC PSPs recorded with either 7 mm (open circles) or 16 mm (closed circles) [Cl−] in the pipette solution. An HFS (arrow at time 0) fails to induce a long-lasting increase in PSP amplitude when a high concentration of chloride is used in the pipette solution (filled circled, p = 0.4103, n = 5) but evokes normal long-term potentiation in control experiments (open circles, p = 0.0047, n = 5). C, Summary graph of experiments performed using the gramicidin-perforated patch-recording configuration. HFS triggers an increase in PSP amplitude (p = 0.008, n = 5) similar to the one observed using whole-cell recording configuration.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596021&req=5

Figure 3: HFS induces a long-term increase of the PSP amplitude in CA2 via a disinhibition mechanism. A, Two representative examples of the normalized PSP time course from CA2 PN whole-cell recordings illustrating how an HFS partially occludes the effect of GABAA and GABAB receptor blocker application on PSP amplitude. Top right, PSP traces corresponding to the time points before (a), after HFS (b), and after the application of GABA receptor blockers (c) with or without HFS. Bottom right, Summary histograms showing the percentage increase in the PSP amplitude induced by HFS applied alone (1), GABA receptor blocker application after HFS (2), HFS plus GABA blockers (1 + 2), and GABA blockers applied without previous HFS (3). B, Normalized CA2 PN SC PSPs recorded with either 7 mm (open circles) or 16 mm (closed circles) [Cl−] in the pipette solution. An HFS (arrow at time 0) fails to induce a long-lasting increase in PSP amplitude when a high concentration of chloride is used in the pipette solution (filled circled, p = 0.4103, n = 5) but evokes normal long-term potentiation in control experiments (open circles, p = 0.0047, n = 5). C, Summary graph of experiments performed using the gramicidin-perforated patch-recording configuration. HFS triggers an increase in PSP amplitude (p = 0.008, n = 5) similar to the one observed using whole-cell recording configuration.
Mentions: If the increase in the PSP after HFS indeed results from a decrease in inhibition, then it is possible to make the following prediction: pharmacological block of inhibition should increase the amplitude of the PSP, and part of this increase should be occluded by a previous HFS. In order to test this, we performed current-clamp recordings of CA2 PNs and applied GABA receptor blockers after an HFS of SC inputs, or in control experiments with no tetanus stimulation. We found that when the GABA receptor blockers were applied without the HFS, the PSP amplitude was strongly increased (Fig. 3A; 472.8 ± 85.5% of the PSP amplitude, p = 0.0026, n = 6), confirming that GABAergic transmission exerts a strong negative control on the PSP amplitude in CA2 PNs (Piskorowski and Chevaleyre, 2013). When the GABA receptor blockers were applied after the HFS, the increase in the PSP amplitude was smaller than the effect of the blockers applied without the HFS [Fig. 3A; 185.8 ± 7.8% of increase of the PSP amplitude, p < 0.00001 (p = 0.0074 compared with blockers without HFS), n = 6]. However, the final PSP amplitude after the HFS and GABA blocker application was identical to the amplitude of the PSP after GABA blocker application alone (Fig. 3A; p = 0.7, n = 6). Altogether, these results indicate that the HFS-induced increase of the PSP amplitude is mediated by a decrease in GABAergic transmission.

Bottom Line: We provide evidence that this effect is mediated by a long-term depression at inhibitory synapses (iLTD), as it is evoked by the same protocols and shares the same pharmacology.The disinhibitory increase in excitatory drive is sufficient to allow CA3 inputs to evoke action potential firing in CA2 PNs.Thus, these data reveal that the output of CA2 PNs can be gated by the unique activity-dependent plasticity of inhibitory neurons in area CA2.

View Article: PubMed Central - HTML - PubMed

Affiliation: Team Synaptic Plasticity and Neural Networks, FR3636, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8118, Université Paris Descartes , Sorbonne Paris Cité, 75006 Paris, France.

ABSTRACT
Area CA2 is emerging as an important region for hippocampal memory formation. However, how CA2 pyramidal neurons (PNs) are engaged by intrahippocampal inputs remains unclear. Excitatory transmission between CA3 and CA2 is strongly inhibited and is not plastic. We show in mice that different patterns of activity can in fact increase the excitatory drive between CA3 and CA2. We provide evidence that this effect is mediated by a long-term depression at inhibitory synapses (iLTD), as it is evoked by the same protocols and shares the same pharmacology. In addition, we show that the net excitatory drive of distal inputs is also increased after iLTD induction. The disinhibitory increase in excitatory drive is sufficient to allow CA3 inputs to evoke action potential firing in CA2 PNs. Thus, these data reveal that the output of CA2 PNs can be gated by the unique activity-dependent plasticity of inhibitory neurons in area CA2.

No MeSH data available.


Related in: MedlinePlus