Multibranch activity in basal and tuft dendrites during firing of layer 5 cortical neurons in vivo

Abstract

Layer 5 pyramidal neurons process information from multiple cortical layers to provide a major output of cortex. Because of technical limitations it has remained unclear how these cells integrate widespread synaptic inputs located in distantly separated basal and tuft dendrites. Here, we obtained in vivo twophoton calcium imaging recordings from the entire dendritic field of layer 5 motor cortex neurons. We demonstrate that during subthreshold activity, basal and tuft dendrites exhibit spatially localized, small-amplitude calcium transients reflecting afferent synaptic inputs. During action potential firing, calcium signals in basal dendrites are linearly related to spike activity, whereas calcium signals in the tuft occur unreliably. However, in both dendritic compartments, spike-associated calcium signals were uniformly distributed throughout all branches. Thus, our data support a model of widespread, multibranch integration with a direct impact by basal dendrites and only a partial contribution on output signaling by the tuft.excitatory synapses | dendritic integration | mouse motor cortex P yramidal neurons feature extensive dendritic arborizations that receive and process widespread synaptic input. Much interest has been placed on the role of individual dendritic branches in determining neuronal output (1). The single branch has been hypothesized to function as a unit of plasticity (2), protein synthesis (3), and synaptic integration (4). Moreover, single dendritic branches have been shown to generate spatially restricted regenerative events, the so-called dendritic spikes, which can process and amplify local input (5). These features raise the question of whether the input-output relation of a cortical neuron is influenced primarily by single dendrites or by multibranch activity.Layer 5 (L5) pyramidal neurons serve as the major output cell type of neocortex. Their morphology is characterized by a set of basal dendrites as well as a set of distal tuft dendrites that extend into layer 1 and are separated from the soma by a long apical trunk (6). These compartments are known to be specialized in terms of the type of synaptic input that they receive (7). Furthermore, in vitro studies of dendritic physiology have revealed several active dendritic signals in these compartments such as back-propagation of action potentials (bAPs) (8, 9), NMDA spikes resulting from clustered synaptic activation (5), and calcium spikes initiated in the apical trunk (10, 11). Despite the presence of these dendritic specializations, little is known about the importance of these features for in vivo function. Previous in vivo studies were limited by the technical challenges of recording from deep basal structures in L5 (12) or of recording multiple individual dendrites simultaneously from the same neuron (13). A complete understanding of dendritic integration in L5 pyramidal neurons requires in vivo data from both the basal and tuft compartments with single dendritic branch resolution.Here we address the question of multibranch activi...

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