Distinct dendritic Ca2+ spike forms produce opposing input-output transformations in rat CA3 pyramidal cells.

Noémi Kis,Ádám Magó,Judit K Makara,Balázs Lükő

doi:10.7554/elife.74493

Noémi Kis, Ádám Magó + Show 2 more

Open Access

https://doi.org/10.7554/elife.74493

Copy DOI

Abstract

Proper integration of different inputs targeting the dendritic tree of CA3 pyramidal cells (CA3PCs) is critical for associative learning and recall. Dendritic Ca2+ spikes have been proposed to perform associative computations in other PC types by detecting conjunctive activation of different afferent input pathways, initiating afterdepolarization (ADP), and triggering burst firing. Implementation of such operations fundamentally depends on the actual biophysical properties of dendritic Ca2+ spikes; yet little is known about these properties in dendrites of CA3PCs. Using dendritic patch-clamp recordings and two-photon Ca2+ imaging in acute slices from male rats, we report that, unlike CA1PCs, distal apical trunk dendrites of CA3PCs exhibit distinct forms of dendritic Ca2+ spikes. Besides ADP-type global Ca2+ spikes, a majority of dendrites expresses a novel, fast Ca2+ spike type that is initiated locally without bAPs, can recruit additional Na+ currents, and is compartmentalized to the activated dendritic subtree. Occurrence of the different Ca2+ spike types correlates with dendritic structure, indicating morpho-functional heterogeneity among CA3PCs. Importantly, ADPs and dendritically initiated spikes produce opposing somatic output: bursts versus strictly single-action potentials, respectively. The uncovered variability of dendritic Ca2+ spikes may underlie heterogeneous input-output transformation and bursting properties of CA3PCs, and might specifically contribute to key associative and non-associative computations performed by the CA3 network.

Highlights

Dendrites play a critical role in the integration and plasticity of synaptic inputs
Using dual soma-dendritic and single-site dendritic patch-c lamp recordings combined with 2P Ca2+ imaging, we reveal complex active properties of CA3 pyramidal cells (CA3PCs) apical dendrites
Besides supporting local Na+ and NMDAR-mediated d-spikes (Brandalise and Gerber, 2014; Kim et al, 2012; Makara and Magee, 2013), we report that these dendrites express distinct types of Ca2+ spikes that can oppositely impact the form of firing by the neuron

Summary

Introduction

Dendrites play a critical role in the integration and plasticity of synaptic inputs. Voltage-dependent ion channels and passive electrical properties of dendrites enable neurons to perform various forms of linear and nonlinear input-o utput transformation. Studies in hippocampal CA1PCs and neocortical layer 5 PCs (L5PCs) have shown that Ca2+ spikes are generated in the main apical trunk efficiently upon widespread synaptic depolarization in distal (tuft) dendrites concomitant with backpropagating action potentials (bAPs), and manifest as an afterdepolarization (ADP) producing a characteristic burst of additional APs ( called complex spike burst [CSB]) at the soma (Harnett et al, 2013; Larkum et al, 2009; Larkum et al, 1999; Takahashi and Magee, 2009) These results led to a concept that Ca2+ spikes can act as an associative dendritic signal that translates a specific input pattern (coincident activation of proximal and distal input pathways) into a burst output (a reliable form of downstream synaptic information transfer; Lisman, 1997) and induce synaptic plasticity (Bittner et al, 2017; Takahashi and Magee, 2009). The question emerges: Do Ca2+ spikes ubiquitously serve such a canonical role in PCs, or do different PC types express Ca2+ spikes with different properties, allowing them to support other input-o utput transformations and computations?

Methods

Results

Conclusion