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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

Stimulation in SR induces a heterosynaptic iLTD and increases distal excitatory drive onto CA2 PNs. A, Cartoon illustrating the arrangement of the stimulating recording electrodes in SR and SLM. B, Average PSP amplitudes of SR (open circles) and SLM (closed circles) inputs after HFS stimulation in SR. Note that both SR and SLM inputs are potentiated after the HFS (p = 0.00035 for SR inputs, p = 0.0017 for SLM inputs, n = 10), but only SR inputs show a rapid post-tetanic increase in amplitude. Top, Averaged PSP traces corresponding to the time points before (a) and after (b) HFS. C, The increase in distally evoked PSP after stimulation in SR was blocked by GABAA and GABAB receptor blockers (open circles, p = 0.52, n = 8) and by the DOR antagonist naltrindol (gray circles, p = 0.31, n = 6). D, Average amplitude of IPSCs evoked by stimulation in SR and SLM after HFS in SR. Note that both inputs express an inhibitory LTD after HFS in SR (p = 0.006 for SR inputs; p = 0.003 for SLM inputs, n = 6).
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Figure 5: Stimulation in SR induces a heterosynaptic iLTD and increases distal excitatory drive onto CA2 PNs. A, Cartoon illustrating the arrangement of the stimulating recording electrodes in SR and SLM. B, Average PSP amplitudes of SR (open circles) and SLM (closed circles) inputs after HFS stimulation in SR. Note that both SR and SLM inputs are potentiated after the HFS (p = 0.00035 for SR inputs, p = 0.0017 for SLM inputs, n = 10), but only SR inputs show a rapid post-tetanic increase in amplitude. Top, Averaged PSP traces corresponding to the time points before (a) and after (b) HFS. C, The increase in distally evoked PSP after stimulation in SR was blocked by GABAA and GABAB receptor blockers (open circles, p = 0.52, n = 8) and by the DOR antagonist naltrindol (gray circles, p = 0.31, n = 6). D, Average amplitude of IPSCs evoked by stimulation in SR and SLM after HFS in SR. Note that both inputs express an inhibitory LTD after HFS in SR (p = 0.006 for SR inputs; p = 0.003 for SLM inputs, n = 6).

Mentions: CA2 PNs are strongly activated by distal inputs in SLM. Thus, we wondered whether the stimulation of proximal SC inputs, via a disinhibitory mechanism, could also influence distal inputs in SLM. We used two stimulating electrodes to evoke PSPs in SC and SLM inputs, as diagrammed in Figure 5A, and checked for the independence of the two pathways before starting experiments (see Materials and Methods). We found that tetanic stimulation in SR not only led to a large increase in the PSP amplitude of SC inputs, but also increased the amplitude of PSPs from SLM inputs (Fig. 5B; 125.9 ± 5.9% of baseline, p = 0.0017 with baseline, n = 10). In contrast to SC inputs, SLM inputs have been described to express an LTP that is independent of inhibitory transmission (Chevaleyre and Siegelbaum, 2010). Thus, we wondered whether our observed increase in SLM PSP is a result of a direct LTP at these inputs or from a disinhibitory mechanism similar to what we have found at SC–CA2 inputs. We repeated the experiment in the presence of GABA receptor blockers and found that the tetanic stimulation in SR did not result in any increase of SLM-evoked PSPs (Fig. 5C; 94.6 ± 7.9% of baseline, p = 0.52 with baseline, n = 8), which is consistent with a disinhibitory mechanism. We then tested whether this disinhibitory mechanism at the SLM pathway also depends on DOR activation by applying the SR tetanus stimulation in the presence of naltrindole. We found that the increase in the PSP amplitude of SLM input was completely blocked under these conditions (Fig. 5C; 103.9 ± 3.4% of baseline, p = 0.31 with baseline, n = 6).


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

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

Stimulation in SR induces a heterosynaptic iLTD and increases distal excitatory drive onto CA2 PNs. A, Cartoon illustrating the arrangement of the stimulating recording electrodes in SR and SLM. B, Average PSP amplitudes of SR (open circles) and SLM (closed circles) inputs after HFS stimulation in SR. Note that both SR and SLM inputs are potentiated after the HFS (p = 0.00035 for SR inputs, p = 0.0017 for SLM inputs, n = 10), but only SR inputs show a rapid post-tetanic increase in amplitude. Top, Averaged PSP traces corresponding to the time points before (a) and after (b) HFS. C, The increase in distally evoked PSP after stimulation in SR was blocked by GABAA and GABAB receptor blockers (open circles, p = 0.52, n = 8) and by the DOR antagonist naltrindol (gray circles, p = 0.31, n = 6). D, Average amplitude of IPSCs evoked by stimulation in SR and SLM after HFS in SR. Note that both inputs express an inhibitory LTD after HFS in SR (p = 0.006 for SR inputs; p = 0.003 for SLM inputs, n = 6).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Stimulation in SR induces a heterosynaptic iLTD and increases distal excitatory drive onto CA2 PNs. A, Cartoon illustrating the arrangement of the stimulating recording electrodes in SR and SLM. B, Average PSP amplitudes of SR (open circles) and SLM (closed circles) inputs after HFS stimulation in SR. Note that both SR and SLM inputs are potentiated after the HFS (p = 0.00035 for SR inputs, p = 0.0017 for SLM inputs, n = 10), but only SR inputs show a rapid post-tetanic increase in amplitude. Top, Averaged PSP traces corresponding to the time points before (a) and after (b) HFS. C, The increase in distally evoked PSP after stimulation in SR was blocked by GABAA and GABAB receptor blockers (open circles, p = 0.52, n = 8) and by the DOR antagonist naltrindol (gray circles, p = 0.31, n = 6). D, Average amplitude of IPSCs evoked by stimulation in SR and SLM after HFS in SR. Note that both inputs express an inhibitory LTD after HFS in SR (p = 0.006 for SR inputs; p = 0.003 for SLM inputs, n = 6).
Mentions: CA2 PNs are strongly activated by distal inputs in SLM. Thus, we wondered whether the stimulation of proximal SC inputs, via a disinhibitory mechanism, could also influence distal inputs in SLM. We used two stimulating electrodes to evoke PSPs in SC and SLM inputs, as diagrammed in Figure 5A, and checked for the independence of the two pathways before starting experiments (see Materials and Methods). We found that tetanic stimulation in SR not only led to a large increase in the PSP amplitude of SC inputs, but also increased the amplitude of PSPs from SLM inputs (Fig. 5B; 125.9 ± 5.9% of baseline, p = 0.0017 with baseline, n = 10). In contrast to SC inputs, SLM inputs have been described to express an LTP that is independent of inhibitory transmission (Chevaleyre and Siegelbaum, 2010). Thus, we wondered whether our observed increase in SLM PSP is a result of a direct LTP at these inputs or from a disinhibitory mechanism similar to what we have found at SC–CA2 inputs. We repeated the experiment in the presence of GABA receptor blockers and found that the tetanic stimulation in SR did not result in any increase of SLM-evoked PSPs (Fig. 5C; 94.6 ± 7.9% of baseline, p = 0.52 with baseline, n = 8), which is consistent with a disinhibitory mechanism. We then tested whether this disinhibitory mechanism at the SLM pathway also depends on DOR activation by applying the SR tetanus stimulation in the presence of naltrindole. We found that the increase in the PSP amplitude of SLM input was completely blocked under these conditions (Fig. 5C; 103.9 ± 3.4% of baseline, p = 0.31 with baseline, n = 6).

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