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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 and 10 Hz stimulation induce a long-term increase of SC–CA2 PSP amplitude. A–D, Time course of the average normalized PSP amplitude obtained by extracellular recording (A, B) in CA2 SR or whole-cell current-clamp recording (C, D) of CA2 PNs, in response to SC stimulation. Both an HFS protocol (two sets of 100 pulses at 100 Hz; A: p < 0.00001, n = 10; C: p = 0.00018, n = 9) and a 10 Hz protocol (two sets of 100 pulses at 10 Hz; B: p = 0.0009, n = 8; D: p = 0.01596, n = 6) induce a long-term increase in the SC PSP amplitude in CA2. The fiber volley (FV; a measure of the number of axons firing an action potential) was not significantly increased after HFS (A; p = 0.06) or 10 Hz stimulation (B; p = 0.19). A also shows that making a cut between CA3 and CA2 does not affect the magnitude of the potentiation evoked by HFS (p = 0.59 with uncut slices, n = 5). Top right-hand corner in all panels, Averaged PSP traces of a representative experiment corresponding to time points before (a) and 60 min after (b; A, B) or 40 min after (b; C, D) the stimulation protocol. Error bars indicate the SEM in all panels.
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Figure 1: HFS and 10 Hz stimulation induce a long-term increase of SC–CA2 PSP amplitude. A–D, Time course of the average normalized PSP amplitude obtained by extracellular recording (A, B) in CA2 SR or whole-cell current-clamp recording (C, D) of CA2 PNs, in response to SC stimulation. Both an HFS protocol (two sets of 100 pulses at 100 Hz; A: p < 0.00001, n = 10; C: p = 0.00018, n = 9) and a 10 Hz protocol (two sets of 100 pulses at 10 Hz; B: p = 0.0009, n = 8; D: p = 0.01596, n = 6) induce a long-term increase in the SC PSP amplitude in CA2. The fiber volley (FV; a measure of the number of axons firing an action potential) was not significantly increased after HFS (A; p = 0.06) or 10 Hz stimulation (B; p = 0.19). A also shows that making a cut between CA3 and CA2 does not affect the magnitude of the potentiation evoked by HFS (p = 0.59 with uncut slices, n = 5). Top right-hand corner in all panels, Averaged PSP traces of a representative experiment corresponding to time points before (a) and 60 min after (b; A, B) or 40 min after (b; C, D) the stimulation protocol. Error bars indicate the SEM in all panels.

Mentions: Inhibition in area CA2 has been shown to play a very prominent role in controlling the size of the depolarizing component of the compound EPSP–IPSP after stimulation of the SC (Piskorowski and Chevaleyre, 2013). Furthermore, inhibition has been shown to be highly plastic, undergoing an iLTD mediated by DORs (Piskorowski and Chevaleyre, 2013). We asked whether this plasticity of inhibitory transmission might be sufficient to modulate the level of excitatory drive at SC–CA2 synapses. To address this question, we first recorded extracellular field PSPs (fPSPs) in CA2 SR in response to electrical stimulation of SC fibers. These fPSPs are a compound readout of both the local EPSPs and IPSPs. After a stable baseline period, we applied either an HFS protocol (100 pulses at 100 Hz repeated twice) or a 10 Hz protocol (100 pulses at 10 Hz repeated twice). These two protocols efficiently induce iLTD of inhibitory inputs in area CA2 (Piskorowski and Chevaleyre, 2013). We found that both the HFS and 10 Hz protocol evoked a lasting increase in the amplitude of the compound fPSP [with 100 Hz stimulation: 160.5 ± 4.2% of fPSP amplitude, p < 0.00001, n = 10 (Fig. 1A); with 10 Hz stimulation: 144.8 ± 9.9% of fPSP amplitude, p = 0.0034, n = 8 (Fig. 1B)]. We also observed a significant but smaller increase in the compound fPSP when measuring the slope (136.2 ± 6.4% of fPSP slope, p = 0.0009, n = 8). We expected a smaller change in the fPSP when measuring the slope, as most of the inhibition evoked by the stimulation is recruited by the SC. The extrasynaptic delay of this feedforward inhibition onto CA2 PNs (compared with the direct SC transmission) will result in a larger control of the peak rather than of the slope of the fPSP. Therefore, the amplitude of the PSP was used for the analysis of the subsequent experiments.


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

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

HFS and 10 Hz stimulation induce a long-term increase of SC–CA2 PSP amplitude. A–D, Time course of the average normalized PSP amplitude obtained by extracellular recording (A, B) in CA2 SR or whole-cell current-clamp recording (C, D) of CA2 PNs, in response to SC stimulation. Both an HFS protocol (two sets of 100 pulses at 100 Hz; A: p < 0.00001, n = 10; C: p = 0.00018, n = 9) and a 10 Hz protocol (two sets of 100 pulses at 10 Hz; B: p = 0.0009, n = 8; D: p = 0.01596, n = 6) induce a long-term increase in the SC PSP amplitude in CA2. The fiber volley (FV; a measure of the number of axons firing an action potential) was not significantly increased after HFS (A; p = 0.06) or 10 Hz stimulation (B; p = 0.19). A also shows that making a cut between CA3 and CA2 does not affect the magnitude of the potentiation evoked by HFS (p = 0.59 with uncut slices, n = 5). Top right-hand corner in all panels, Averaged PSP traces of a representative experiment corresponding to time points before (a) and 60 min after (b; A, B) or 40 min after (b; C, D) the stimulation protocol. Error bars indicate the SEM in all panels.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: HFS and 10 Hz stimulation induce a long-term increase of SC–CA2 PSP amplitude. A–D, Time course of the average normalized PSP amplitude obtained by extracellular recording (A, B) in CA2 SR or whole-cell current-clamp recording (C, D) of CA2 PNs, in response to SC stimulation. Both an HFS protocol (two sets of 100 pulses at 100 Hz; A: p < 0.00001, n = 10; C: p = 0.00018, n = 9) and a 10 Hz protocol (two sets of 100 pulses at 10 Hz; B: p = 0.0009, n = 8; D: p = 0.01596, n = 6) induce a long-term increase in the SC PSP amplitude in CA2. The fiber volley (FV; a measure of the number of axons firing an action potential) was not significantly increased after HFS (A; p = 0.06) or 10 Hz stimulation (B; p = 0.19). A also shows that making a cut between CA3 and CA2 does not affect the magnitude of the potentiation evoked by HFS (p = 0.59 with uncut slices, n = 5). Top right-hand corner in all panels, Averaged PSP traces of a representative experiment corresponding to time points before (a) and 60 min after (b; A, B) or 40 min after (b; C, D) the stimulation protocol. Error bars indicate the SEM in all panels.
Mentions: Inhibition in area CA2 has been shown to play a very prominent role in controlling the size of the depolarizing component of the compound EPSP–IPSP after stimulation of the SC (Piskorowski and Chevaleyre, 2013). Furthermore, inhibition has been shown to be highly plastic, undergoing an iLTD mediated by DORs (Piskorowski and Chevaleyre, 2013). We asked whether this plasticity of inhibitory transmission might be sufficient to modulate the level of excitatory drive at SC–CA2 synapses. To address this question, we first recorded extracellular field PSPs (fPSPs) in CA2 SR in response to electrical stimulation of SC fibers. These fPSPs are a compound readout of both the local EPSPs and IPSPs. After a stable baseline period, we applied either an HFS protocol (100 pulses at 100 Hz repeated twice) or a 10 Hz protocol (100 pulses at 10 Hz repeated twice). These two protocols efficiently induce iLTD of inhibitory inputs in area CA2 (Piskorowski and Chevaleyre, 2013). We found that both the HFS and 10 Hz protocol evoked a lasting increase in the amplitude of the compound fPSP [with 100 Hz stimulation: 160.5 ± 4.2% of fPSP amplitude, p < 0.00001, n = 10 (Fig. 1A); with 10 Hz stimulation: 144.8 ± 9.9% of fPSP amplitude, p = 0.0034, n = 8 (Fig. 1B)]. We also observed a significant but smaller increase in the compound fPSP when measuring the slope (136.2 ± 6.4% of fPSP slope, p = 0.0009, n = 8). We expected a smaller change in the fPSP when measuring the slope, as most of the inhibition evoked by the stimulation is recruited by the SC. The extrasynaptic delay of this feedforward inhibition onto CA2 PNs (compared with the direct SC transmission) will result in a larger control of the peak rather than of the slope of the fPSP. Therefore, the amplitude of the PSP was used for the analysis of the subsequent experiments.

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