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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

The HFS-induced long-term potentiation of the PSP in CA2 is dependent on GABAergic transmission. A, Time course of average normalized fPSP amplitude recorded in CA1 SR in response to SC stimulation, showing that the HFS-induced increase in PSP amplitude in control conditions (open circles, p = 0.0020, n = 5) was facilitated in the continuous presence of the GABAA and GABAB receptor antagonists 1 μm SR 95531 and 2 μm CGP 55845 (filled circles, p = 0.0017, n = 8). B, C, In CA2, HFS does not trigger long-lasting increase in the SC PSP amplitude in the continuous presence of GABA receptor antagonists (filled circles; B, extracellular recordings, p = 0.09, n = 10; C, whole-cell recording, p = 0.6997, n = 10), but evokes a large and lasting increase in the PSP amplitude in control experiments (open circles; B, extracellular recordings, p < 0.00001, n = 10; C, whole-cell recording, p < 0.00001, n = 10). In all panels, averaged PSP traces corresponding to the time points before (a) and after (b) HFS are shown on the right. Error bars indicate the SEM in all panels.
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Figure 2: The HFS-induced long-term potentiation of the PSP in CA2 is dependent on GABAergic transmission. A, Time course of average normalized fPSP amplitude recorded in CA1 SR in response to SC stimulation, showing that the HFS-induced increase in PSP amplitude in control conditions (open circles, p = 0.0020, n = 5) was facilitated in the continuous presence of the GABAA and GABAB receptor antagonists 1 μm SR 95531 and 2 μm CGP 55845 (filled circles, p = 0.0017, n = 8). B, C, In CA2, HFS does not trigger long-lasting increase in the SC PSP amplitude in the continuous presence of GABA receptor antagonists (filled circles; B, extracellular recordings, p = 0.09, n = 10; C, whole-cell recording, p = 0.6997, n = 10), but evokes a large and lasting increase in the PSP amplitude in control experiments (open circles; B, extracellular recordings, p < 0.00001, n = 10; C, whole-cell recording, p < 0.00001, n = 10). In all panels, averaged PSP traces corresponding to the time points before (a) and after (b) HFS are shown on the right. Error bars indicate the SEM in all panels.

Mentions: To test this hypothesis, we recorded extracellular compound fPSPs in areas CA1 and CA2 in response to HFS of SC inputs either in the presence or absence of GABAA and GABAB receptor antagonists (1 µm SR 95531 and 2 µm CGP 55845). In area CA1, the HFS induced a small increase in the fPSP amplitude when inhibition was intact (Fig. 2A; 128.2 ± 4.1% of fPSP amplitude, p = 0.0020, n = 5). As expected, this increase was significantly enhanced when the recordings were performed in the continuous presence of GABA receptor antagonists [Fig. 2A; 167.9 ± 13.4%, p = 0.0017 (p = 0.0447 with intact inhibition), n = 8]. In area CA2, a robust and lasting increase of the fPSP was induced with inhibition intact (Fig. 2B; 160.5 ± 4.2% of PSP basal amplitude, p < 0.00001, n = 10). Furthermore, unlike what was observed in area CA1, the HFS did not evoke any lasting change in the fPSP amplitude when inhibitory transmission was blocked [Fig. 2B; 104.9 ± 2.3% of EPSP amplitude, p = 0.09 (p < 0.0001 with intact inhibition), n = 10].


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

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

The HFS-induced long-term potentiation of the PSP in CA2 is dependent on GABAergic transmission. A, Time course of average normalized fPSP amplitude recorded in CA1 SR in response to SC stimulation, showing that the HFS-induced increase in PSP amplitude in control conditions (open circles, p = 0.0020, n = 5) was facilitated in the continuous presence of the GABAA and GABAB receptor antagonists 1 μm SR 95531 and 2 μm CGP 55845 (filled circles, p = 0.0017, n = 8). B, C, In CA2, HFS does not trigger long-lasting increase in the SC PSP amplitude in the continuous presence of GABA receptor antagonists (filled circles; B, extracellular recordings, p = 0.09, n = 10; C, whole-cell recording, p = 0.6997, n = 10), but evokes a large and lasting increase in the PSP amplitude in control experiments (open circles; B, extracellular recordings, p < 0.00001, n = 10; C, whole-cell recording, p < 0.00001, n = 10). In all panels, averaged PSP traces corresponding to the time points before (a) and after (b) HFS are shown on the right. Error bars indicate the SEM in all panels.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 2: The HFS-induced long-term potentiation of the PSP in CA2 is dependent on GABAergic transmission. A, Time course of average normalized fPSP amplitude recorded in CA1 SR in response to SC stimulation, showing that the HFS-induced increase in PSP amplitude in control conditions (open circles, p = 0.0020, n = 5) was facilitated in the continuous presence of the GABAA and GABAB receptor antagonists 1 μm SR 95531 and 2 μm CGP 55845 (filled circles, p = 0.0017, n = 8). B, C, In CA2, HFS does not trigger long-lasting increase in the SC PSP amplitude in the continuous presence of GABA receptor antagonists (filled circles; B, extracellular recordings, p = 0.09, n = 10; C, whole-cell recording, p = 0.6997, n = 10), but evokes a large and lasting increase in the PSP amplitude in control experiments (open circles; B, extracellular recordings, p < 0.00001, n = 10; C, whole-cell recording, p < 0.00001, n = 10). In all panels, averaged PSP traces corresponding to the time points before (a) and after (b) HFS are shown on the right. Error bars indicate the SEM in all panels.
Mentions: To test this hypothesis, we recorded extracellular compound fPSPs in areas CA1 and CA2 in response to HFS of SC inputs either in the presence or absence of GABAA and GABAB receptor antagonists (1 µm SR 95531 and 2 µm CGP 55845). In area CA1, the HFS induced a small increase in the fPSP amplitude when inhibition was intact (Fig. 2A; 128.2 ± 4.1% of fPSP amplitude, p = 0.0020, n = 5). As expected, this increase was significantly enhanced when the recordings were performed in the continuous presence of GABA receptor antagonists [Fig. 2A; 167.9 ± 13.4%, p = 0.0017 (p = 0.0447 with intact inhibition), n = 8]. In area CA2, a robust and lasting increase of the fPSP was induced with inhibition intact (Fig. 2B; 160.5 ± 4.2% of PSP basal amplitude, p < 0.00001, n = 10). Furthermore, unlike what was observed in area CA1, the HFS did not evoke any lasting change in the fPSP amplitude when inhibitory transmission was blocked [Fig. 2B; 104.9 ± 2.3% of EPSP amplitude, p = 0.09 (p < 0.0001 with intact inhibition), n = 10].

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