Mechanisms of Supralinear Calcium Integration in Dendrites of Hippocampal CA1 Fast-Spiking Cells

Abstract

In fast-spiking (FS), parvalbumin-expressing interneurons of the CA1 hippocampus, activation of the GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPARs) in basal dendrites is coupled to Ca2+-induced Ca2+-release (CICR), and can result in a supralinear summation of postsynaptic Ca2+-transients (post-CaTs). While this mechanism is important in controlling the direction of long-term plasticity, it is still unknown whether it can operate at all excitatory synapses converging onto FS cells or at a set of synapses receiving a particular input. Using a combination of patch-clamp recordings and two-photon Ca2+ imaging in acute mouse hippocampal slices with computational simulations, here we compared the generation of supralinear post-CaTs between apical and basal dendrites of FS cells. We found that, similar to basal dendrites, apical post-CaTs summated supralinearly and relied mainly on the activation of the CP-AMPARs, with a variable contribution of other Ca2+ sources, such as NMDA receptors, L-type voltage-gated Ca2+-channels and Ca2+ release. In addition, supralinear post-CaTs generated in apical dendrites had a slower decay time and a larger cumulative charge than those in basal, and were associated with a stronger level of somatic depolarization. The model predicted that modulation of ryanodine receptors and of the Ca2+ extrusion mechanisms, such as the Na+/Ca2+-exchanger and SERCA pump, had a major impact on the magnitude of supralinear post-CaTs. These data reveal that supralinear Ca2+ summation is a common mechanism of Ca2+ signaling at CP-AMPAR-containing synapses. Shaped in a location-specific manner through modulation of ryanodine receptors and Ca2+ extrusion mechanisms, CP-AMPAR/CICR signaling is suitable for synapse-specific bidirectional modification of incoming inputs in the absence of active dendritic conductances.

Structural analysis of the microglia–interneuron interactions in the CA1 hippocampal area of the APP/PS1 mouse model of Alzheimer's disease

“…These data revealed that, while both interneuron types received the Process MG ‐to‐Dend IN putative contacts mostly on proximal dendrites (within the first 20 μm; Figure 3d), those made onto dendrites of PV+ cells were found at a longer distance from the soma than in SOM+ cells (PV+: 28.5 ± 2.8 μm, n = 45 interneurons/22 slices/three mice; SOM+: 17.6 ± 1.2 μm, n = 60 interneurons/18 slices/three mice; p = .001, Mann–Whitney test,). Therefore, the smaller Process MG ‐to‐Dend IN interaction area for PV+ cells could result in part from the decrease in thickness of PV+ dendrites with distance from the soma (Camiré et al., 2018). Furthermore, we investigated the possible relationship between the area of the Process MG ‐to‐Dend IN interaction and distance from the soma (Figure 3e).…”

Synaptic Plasticity in Cortical Inhibitory Neurons: What Mechanisms May Help to Balance Synaptic Weight Changes?

“…Ultimately, dynamics of [Ca 2+ ] i in interneurons is determined by the interaction between multiple ligand-gated and voltage-gated sources of calcium influx described above as well as additional factors, such as calcium release from internal stores (e.g., Goldberg et al, 2003a ; Topolnik et al, 2009 ; Evstratova et al, 2011 ; Camiré and Topolnik, 2014 ; Camiré et al, 2018 ) and internal calcium buffering and extrusion (Goldberg et al, 2003a ; Rozsa et al, 2004 ; Evstratova et al, 2011 ; Matthews et al, 2013 ; Matthews and Dietrich, 2015 ; Chamberland et al, 2019 ).…”

“…In contrast, [Ca 2+ ] i rise mediated by the CP-AMPARs is reduced by the spikes because of the decreasing driving force and eventual polyamine block at depolarized potentials (Rozov and Burnashev, 1999 ; Hainmüller et al, 2014 ; Sancho and Bloodgood, 2018 ). In FS interneurons from hippocampal CA1, strong stimulation of multiple presynaptic fibers can lead to supralinear summation of CP-AMPAR-mediated calcium signals due to calcium release from internal stores (Camiré and Topolnik, 2014 ; Camiré et al, 2018 ). Release from internal stores could also amplify calcium signals evoked by bAPs in several types of CA1 interneurons: CCK-positive basket cells and Schaffer collateral-associated cells from str.…”

Extracellular ATP inhibits excitatory synaptic input on parvalbumin positive interneurons and attenuates gamma oscillations via P2X4 receptors

“…The predominant AMPA receptor in the synapse is the GluA1/GluA4 heteromer (Fuchs et al, 2007;Geiger et al, 1995) which is Ca 2+ -permeable and responsible for the fast kinetics of the EPSCs (Geiger et al, 1997). The inputs have an NMDA receptor component (Fuchs et al, 2007;Papp et al, 2013) which is slower and more variable depending on site and cell type (Camiré et al, 2018;Nyíri et al, 2003). Changes to the excitatory inputs onto PVINs are modulated by the postsynaptic rise in [Ca 2+ ] in their thin aspiny apical dendrites (Bannon et al, 2020;Lamsa et al, 2007).…”