Dataset Information

A simulation study on the effects of dendritic morphology on layer V prefrontal pyramidal cell firing behavior.

ABSTRACT: Pyramidal cells, the most abundant neurons in neocortex, exhibit significant structural variability across different brain areas and layers in different species. Moreover, in response to a somatic step current, these cells display a range of firing behaviors, the most common being (1) repetitive action potentials (Regular Spiking-RS), and (2) an initial cluster of 2-5 action potentials with short interspike interval (ISIs) followed by single spikes (Intrinsic Bursting-IB). A correlation between firing behavior and dendritic morphology has recently been reported. In this work we use computational modeling to investigate quantitatively the effects of the basal dendritic tree morphology on the firing behavior of 112 three-dimensional reconstructions of layer V PFC rat pyramidal cells. Particularly, we focus on how different morphological (diameter, total length, volume, and branch number) and passive [Mean Electrotonic Path length (MEP)] features of basal dendritic trees shape somatic firing when the spatial distribution of ionic mechanisms in the basal dendritic trees is uniform or non-uniform. Our results suggest that total length, volume and branch number are the best morphological parameters to discriminate the cells as RS or IB, regardless of the distribution of ionic mechanisms in basal trees. The discriminatory power of total length, volume, and branch number remains high in the presence of different apical dendrites. These results suggest that morphological variations in the basal dendritic trees of layer V pyramidal neurons in the PFC influence their firing patterns in a predictive manner and may in turn influence the information processing capabilities of these neurons.

SUBMITTER: Psarrou M

PROVIDER: S-EPMC4165233 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A simulation study on the effects of dendritic morphology on layer V prefrontal pyramidal cell firing behavior.

Psarrou Maria M Stefanou Stefanos S SS Papoutsi Athanasia A Tzilivaki Alexandra A Cutsuridis Vassilis V Poirazi Panayiota P

Frontiers in cellular neuroscience 20140916

Pyramidal cells, the most abundant neurons in neocortex, exhibit significant structural variability across different brain areas and layers in different species. Moreover, in response to a somatic step current, these cells display a range of firing behaviors, the most common being (1) repetitive action potentials (Regular Spiking-RS), and (2) an initial cluster of 2-5 action potentials with short interspike interval (ISIs) followed by single spikes (Intrinsic Bursting-IB). A correlation between ...[more]

PMID: 25278837

Similar Datasets

Project description:Neurons display a wide range of intrinsic firing patterns. A particularly relevant pattern for neuronal signaling and synaptic plasticity is burst firing, the generation of clusters of action potentials with short interspike intervals. Besides ion-channel composition, dendritic morphology appears to be an important factor modulating firing pattern. However, the underlying mechanisms are poorly understood, and the impact of morphology on burst firing remains insufficiently known. Dendritic morphology is not fixed but can undergo significant changes in many pathological conditions. Using computational models of neocortical pyramidal cells, we here show that not only the total length of the apical dendrite but also the topological structure of its branching pattern markedly influences inter- and intraburst spike intervals and even determines whether or not a cell exhibits burst firing. We found that there is only a range of dendritic sizes that supports burst firing, and that this range is modulated by dendritic topology. Either reducing or enlarging the dendritic tree, or merely modifying its topological structure without changing total dendritic length, can transform a cell's firing pattern from bursting to tonic firing. Interestingly, the results are largely independent of whether the cells are stimulated by current injection at the soma or by synapses distributed over the dendritic tree. By means of a novel measure called mean electrotonic path length, we show that the influence of dendritic morphology on burst firing is attributable to the effect both dendritic size and dendritic topology have, not on somatic input conductance, but on the average spatial extent of the dendritic tree and the spatiotemporal dynamics of the dendritic membrane potential. Our results suggest that alterations in size or topology of pyramidal cell morphology, such as observed in Alzheimer's disease, mental retardation, epilepsy, and chronic stress, could change neuronal burst firing and thus ultimately affect information processing and cognition.

Project description:The influence of cortical cell spiking activity on nearby cells has been studied extensively in vitro. Less is known, however, about the impact of single cell firing on local cortical networks in vivo. In a pioneering study, Kwan and Dan (Kwan and Dan, 2012) reported that in mouse layer 2/3 (L2/3), under anesthesia, stimulating a single pyramidal cell recruits ~2.1% of neighboring units. Here we employ two-photon calcium imaging in layer 2/3 of mouse V1, in conjunction with single-cell patch clamp stimulation in layer 2/3 or layer 4, to probe, in both the awake and lightly anesthetized states, how (i) activating single L2/3 pyramidal neurons recruits neighboring units within L2/3 and from layer 4 (L4) to L2/3, and whether (ii) activating single pyramidal neurons changes population activity in local circuit. To do this, it was essential to develop an algorithm capable of quantifying how sensitive the calcium signal is at detecting effectively recruited units ("followers"). This algorithm allowed us to estimate the chance of detecting a follower as a function of the probability that an epoch of stimulation elicits one extra action potential (AP) in the follower cell. Using this approach, we found only a small fraction (<0.75%) of L2/3 cells to be significantly activated within a radius of ~200 ?m from a stimulated neighboring L2/3 pyramidal cell. This fraction did not change significantly in the awake vs. the lightly anesthetized state, nor when stimulating L2/3 vs. underlying L4 pyramidal neurons. These numbers are in general agreement with, though lower than, the percentage of neighboring cells (2.1% pyramidal cells and interneurons combined) reported by Kwan and Dan to be activated upon stimulating single L2/3 pyramidal neurons under anesthesia (Kwan and Dan, 2012). Interestingly, despite the small number of individual units found to be reliably driven, we did observe a modest but significant elevation in aggregate population responses compared to sham stimulation. This underscores the distributed impact that single cell stimulation has on neighboring microcircuit responses, revealing only a small minority of relatively strongly connected partners.One sentence summaryPatch-clamp stimulation in conjunction with 2-photon imaging shows that activating single layer-2/3 or layer-4 pyramidal neurons produces few (<1% of local units) reliable single-cell followers in L2/3 of mouse area V1, either under light anesthesia or in quiet wakefulness: instead, single cell stimulation was found to elevate aggregate population activity in a weak but highly distributed fashion.

Project description:In this study, we present a theoretical framework combining experimental characterizations and analytical calculus to capture the firing rate input-output properties of single neurons in the fluctuation-driven regime. Our framework consists of a two-step procedure to treat independently how the dendritic input translates into somatic fluctuation variables, and how the latter determine action potential firing. We use this framework to investigate the functional impact of the heterogeneity in firing responses found experimentally in young mice layer V pyramidal cells. We first design and calibrate in vitro a simplified morphological model of layer V pyramidal neurons with a dendritic tree following Rall's branching rule. Then, we propose an analytical derivation for the membrane potential fluctuations at the soma as a function of the properties of the synaptic input in dendrites. This mathematical description allows us to easily emulate various forms of synaptic input: either balanced, unbalanced, synchronized, purely proximal or purely distal synaptic activity. We find that those different forms of dendritic input activity lead to various impact on the somatic membrane potential fluctuations properties, thus raising the possibility that individual neurons will differentially couple to specific forms of activity as a result of their different firing response. We indeed found such a heterogeneous coupling between synaptic input and firing response for all types of presynaptic activity. This heterogeneity can be explained by different levels of cellular excitability in the case of the balanced, unbalanced, synchronized and purely distal activity. A notable exception appears for proximal dendritic inputs: increasing the input level can either promote firing response in some cells, or suppress it in some other cells whatever their individual excitability. This behavior can be explained by different sensitivities to the speed of the fluctuations, which was previously associated to different levels of sodium channel inactivation and density. Because local network connectivity rather targets proximal dendrites, our results suggest that this aspect of biophysical heterogeneity might be relevant to neocortical processing by controlling how individual neurons couple to local network activity.

Project description:Architectonic heterogeneity in neurons is thought to be important for equipping the mammalian cerebral cortex with an adaptable network that can organize the manifold totality of information it receives. To this end, the dendritic arbors of supragranular pyramidal neurons, even those of the same class, are known to vary substantially. This diversity of dendritic morphology appears to have a rostrocaudal configuration in some brain regions of various species. For example, in humans and non-human primates, neurons in more rostral visual association areas (e.g., V4) tend to have more complex dendritic arbors than those in the caudal primary visual cortex. A rostrocaudal configuration is not so clear in any region of the mouse, which is increasingly being used as a model for neurodevelopmental disorders that arise from dysfunctional cerebral cortical circuits. Therefore, in this study we investigated the complexity of dendritic arbors of neurons distributed throughout a broad area of the mouse cerebral cortex. We reduced selection bias by labeling neurons restricted to become supragranular pyramidal neurons using in utero electroporation. While we observed that the simple rostrocaudal position, cortical depth, or even functional region of a neuron was not directly related to its dendritic morphology, a model that instead included a caudomedial-to-rostrolateral gradient accounted for a significant amount of the observed dendritic morphological variance. In other words, rostrolateral neurons from our data set were generally more complex when compared to caudomedial neurons. Furthermore, dividing the cortex into a visual area and a non-visual area maintained the power of the relationship between caudomedial-to-rostrolateral position and dendritic complexity. Our observations therefore support the idea that dendritic morphology of mouse supragranular excitatory pyramidal neurons across much of the tangential plane of the cerebral cortex is partly shaped by a developmental gradient spanning several functional regions.

Dataset Information

A simulation study on the effects of dendritic morphology on layer V prefrontal pyramidal cell firing behavior.

Publications

A simulation study on the effects of dendritic morphology on layer V prefrontal pyramidal cell firing behavior.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets