Spiny Dendrites Research Articles

Three-Dimensional Analysis of Spiny Dendrites Using Straightening and Unrolling Transforms

Current understanding of the synaptic organization of the brain depends to a large extent on knowledge about the synaptic inputs to the neurons. Indeed, the dendritic surfaces of pyramidal cells (the most common neuron in the cerebral cortex) are covered by thin protrusions named dendritic spines. These represent the targets of most excitatory synapses in the cerebral cortex and therefore, dendritic spines prove critical in learning, memory and cognition. This paper presents a new method that facilitates the analysis of the 3D structure of spine insertions in dendrites, providing insight on spine distribution patterns. This method is based both on the implementation of straightening and unrolling transformations to move the analysis process to a planar, unfolded arrangement, and on the design of DISPINE, an interactive environment that supports the visual analysis of 3D patterns.

Propagation of CaMKII translocation waves in heterogeneous spiny dendrites

CaMKII (Ca²⁺-calmodulin-dependent protein kinase II) is a key regulator of glutamatergic synapses and plays an essential role in many forms of synaptic plasticity. It has recently been observed experimentally that stimulating a local region of dendrite not only induces the local translocation of CaMKII from the dendritic shaft to synaptic targets within spines, but also initiates a wave of CaMKII translocation that spreads distally through the dendrite with an average speed of order 1 μm/s. We have previously developed a simple reaction-diffusion model of CaMKII translocation waves that can account for the observed wavespeed and predicts wave propagation failure if the density of spines is too high. A major simplification of our previous model was to treat the distribution of spines as spatially uniform. However, there are at least two sources of heterogeneity in the spine distribution that occur on two different spatial scales. First, spines are discrete entities that are joined to a dendritic branch via a thin spine neck of submicron radius, resulting in spatial variations in spine density at the micron level. The second source of heterogeneity occurs on a much longer length scale and reflects the experimental observation that there is a slow proximal to distal variation in the density of spines. In this paper, we analyze how both sources of heterogeneity modulate the speed of CaMKII translocation waves along a spiny dendrite. We adapt methods from the study of the spread of biological invasions in heterogeneous environments, including homogenization theory of pulsating fronts and Hamilton-Jacobi dynamics of sharp interfaces.

Denritic Morphology

The common assumption that dendrites are cylindrical is incorrect. Analyses of spiny stellate cell dendrites reconstructed from serial thin sections through mouse barrels shows these dendrites to be flattened; the ratio of long to short axes in cross‐section is typically 2:1. Planes of flattening are unrelated to the orientation of dendritic segments, are not related to plane of section, and are unchanged for various estimates of section thickness. Thus, the flattened shape is due neither to tissue compression, sectioning artifact, nor to inaccuracy of reconstruction. Two‐thirds of dendritic spines are attached at the narrow, ridge‐like regions of the flattened shafts. Apical dendrites of pyramidal cells are also flattened and exhibit a preferential distribution of spines. These phenomena may be related to the distribution of cytoskeletal elements. The flattened shape may be an artifact of fixation, and if so, could be imagined to result from the shrinking of cell membrane around the cytoskeleton and/or from the collapse of cytoskeletal elements within certain compartments. Alternatively, the shape may reflect the in vivo condition. Consequences for various aspects of electrical activity within dendrites of the possible compartmentalization of the dendroplasm and of the observed irregular distribution of spines remain to be determined. Israel Science Foundation grant 52/00‐4

Subcellular Location of PKA Controls Striatal Plasticity: Stochastic Simulations in Spiny Dendrites

Dopamine release in the striatum has been implicated in various forms of reward dependent learning. Dopamine leads to production of cAMP and activation of protein kinase A (PKA), which are involved in striatal synaptic plasticity and learning. PKA and its protein targets are not diffusely located throughout the neuron, but are confined to various subcellular compartments by anchoring molecules such as A-Kinase Anchoring Proteins (AKAPs). Experiments have shown that blocking the interaction of PKA with AKAPs disrupts its subcellular location and prevents LTP in the hippocampus and striatum; however, these experiments have not revealed whether the critical function of anchoring is to locate PKA near the cAMP that activates it or near its targets, such as AMPA receptors located in the post-synaptic density. We have developed a large scale stochastic reaction-diffusion model of signaling pathways in a medium spiny projection neuron dendrite with spines, based on published biochemical measurements, to investigate this question and to evaluate whether dopamine signaling exhibits spatial specificity post-synaptically. The model was stimulated with dopamine pulses mimicking those recorded in response to reward. Simulations show that PKA colocalization with adenylate cyclase, either in the spine head or in the dendrite, leads to greater phosphorylation of DARPP-32 Thr34 and AMPA receptor GluA1 Ser845 than when PKA is anchored away from adenylate cyclase. Simulations further demonstrate that though cAMP exhibits a strong spatial gradient, diffusible DARPP-32 facilitates the spread of PKA activity, suggesting that additional inactivation mechanisms are required to produce spatial specificity of PKA activity.

Barriers to Diffusion in Dendrites and Estimation of Calcium Spread Following Synaptic Inputs

The motion of ions, molecules or proteins in dendrites is restricted by cytoplasmic obstacles such as organelles, microtubules and actin network. To account for molecular crowding, we study the effect of diffusion barriers on local calcium spread in a dendrite. We first present a model based on a dimension reduction approach to approximate a three dimensional diffusion in a cylindrical dendrite by a one-dimensional effective diffusion process. By comparing uncaging experiments of an inert dye in a spiny dendrite and in a thin glass tube, we quantify the change in diffusion constants due to molecular crowding as Dcyto/Dwater = 1/20. We validate our approach by reconstructing the uncaging experiments using Brownian simulations in a realistic 3D model dendrite. Finally, we construct a reduced reaction-diffusion equation to model calcium spread in a dendrite under the presence of additional buffers, pumps and synaptic input. We find that for moderate crowding, calcium dynamics is mainly regulated by the buffer concentration, but not by the cytoplasmic crowding, dendritic spines or synaptic inputs. Following high frequency stimulations, we predict that calcium spread in dendrites is limited to small microdomains of the order of a few microns (<5 μm).

A Major Role for Intracortical Circuits in the Strength and Tuning of Odor-Evoked Excitation in Olfactory Cortex

In primary sensory cortices, there are two main sources of excitation: afferent sensory input relayed from the periphery and recurrent intracortical input. Untangling the functional roles of these two excitatory pathways is fundamental for understanding how cortical neurons process sensory stimuli. Odor representations in the primary olfactory (piriform) cortex depend on excitatory sensory afferents from the olfactory bulb. However, piriform cortex pyramidal cells also receive dense intracortical excitatory connections, and the relative contribution of these two pathways to odor responses is unclear. Using a combination of in vivo whole-cell voltage-clamp recording and selective synaptic silencing, we show that the recruitment of intracortical input, rather than olfactory bulb input, largely determines the strength of odor-evoked excitatory synaptic transmission in rat piriform cortical neurons. Furthermore, we find that intracortical synapses dominate odor-evoked excitatory transmission in broadly tuned neurons, whereas bulbar synapses dominate excitatory synaptic responses in more narrowly tuned neurons.

Anomalous diffusion imposed by dendritic spines (Commentary on Santamaria et al.)

An exciting decade of two-photon fluorescence imaging has revealed that the shape and turnover of dendritic spines are dynamic and modulated by synaptic plasticity (Matsuzaki et al., 2004). Such structural changes can be induced via focal glutamate uncaging at individual spines, but they can also be driven by experience (Holtmaat et al., 2006). Indeed, the size of both the head and neck of dendritic spines can be modulated by neuronal activity (Matsuzaki et al., 2004; Bloodgood & Sabatini, 2005). In turn, the geometry of spines will affect the compartmentalization of signals generated at the spine head and the extent to which ions and second messengers can spread via the neck to the parent dendrite and nearby spines. Interestingly, Santamaria et al. (2006) demonstrated in an earlier study that diffusion in spiny dendrites cannot be described by the standard diffusion equation. Instead, spines temporarily ‘trap’ molecules causing anomalous diffusion in the parent dendrite (Fig. 1). Uncaging dextran-conjugated fluorescent probes and imaging the fluorescence changes over time along a stretch of dendrite enabled calculation of the spatial variance of the diffusing molecules and estimation of the anomalous exponent dw. In smooth dendrites diffusion had an anomalous exponent of dw = 2, whereas in spiny dendrites dw turned out to be high (dw > 2) resulting in slowed diffusion. The importance of this finding is that the diffusion of second messengers within dendrites could be controlled by changes in spine shape or density. It is known that spine density in CA1 pyramidal neurons varies considerably across their dendritic arbors, with a progressive increase in spine density and spine size in the distal segments of apical dendrites (Konur et al., 2003). Thus, different dendritic compartments may exhibit different rates of diffusion of postsynaptic signaling molecules. In their study published in this issue of EJN, Santamaria et al. (2011) show that, in both Purkinje cells and CA1 pyramidal neurons, the anomalous exponent dw scales linearly with spine density. Anomalous diffusion in dendrites appears to be a hallmark of all neurons with spines. In addition, these authors provide empirical evidence that neither branching geometry nor dendrite diameter account for anomalous diffusion, confirming their previous theoretical models (Santamaria et al., 2006). The mechanistic studies by Santamaria et al. (2011) might be relevant to explain, for example, the functional impact of estradiol on memory formation (Andreescu et al., 2007) or of the pathological impact of a lack of fragile X mental retardation protein on motor behavior (Koekkoek et al., 2005). In both cases, altered geometry of spines and ⁄ or their inputs are likely to affect the diffusion of second messengers in the dendritic network. Therefore, it will be of general interest to identify the molecules for which anomalous diffusion plays a relevant role under physiological and pathophysiological conditions. For instance, active extrusion of calcium is likely to supersede the effects of spine geometry on diffusion of this ion in dendrites, whereas diffusion of inositol triphosphate (IP3) is slowed down (Santamaria et al., 2006) and that of GTPase signaling proteins varies among their family (Yasuda & Murakoshi, 2011). Anomalous diffusion imposed by spine geometry may thus represent a mechanism modulating the function of a selected set of signaling molecules.

The diffusional properties of dendrites depend on the density of dendritic spines

We combined computational modeling and experimental measurements to determine the influence of dendritic structure on the diffusion of intracellular chemical signals in mouse cerebellar Purkinje cells and hippocamal CA1 pyramidal cells. Modeling predicts that molecular trapping by dendritic spines causes diffusion along spiny dendrites to be anomalous and that the value of the anomalous exponent (d(w) ) is proportional to spine density in both cell types. To test these predictions we combined the local photorelease of an inert dye, rhodamine dextran, with two-photon fluorescence imaging to track diffusion along dendrites. Our results show that anomalous diffusion is present in spiny dendrites of both cell types. Further, the anomalous exponent is linearly related to the density of spines in pyramidal cells and d(w) in Purkinje cells is consistent with such a relationship. We conclude that anomalous diffusion occurs in the dendrites of multiple types of neurons. Because spine density is dynamic and depends on neuronal activity, the degree of anomalous diffusion induced by spines can dynamically regulate the movement of molecules along dendrites.

A stochastic model describing transport of PSD-95 molecules in spiny dendrites provides the basis for synaptic plasticity

Molecules in neurons are in a state far from equilibrium. Therefore their transport properties are strongly affected by fluctuations. We present a model of stochastic molecular transport in neurons which have their synapses located in the spines of a dendrite. In this model we assume that the molecules perform a random walk between the spines that trap the walkers. If the molecules are assumed to interact with each other inside the spines, the trapping time in each spine depends on the number of molecules in the respective trap. The corresponding mathematical problem has non-trivial solutions even in the absence of external disorder due to self-organization phenomena. We obtain the stationary distributions of the number of walkers in the traps for different kinds of on-site interactions between the walkers and furthermore analyze how birth and death processes of the random walkers affect these distributions. We apply this model to describe the dynamics of the PSD-95 proteins in spiny dendrites. PSD-95 is the most abundant molecule in the post-synaptic density (PSD) located in the spines. It is observed that these molecules have high turnover rates and that neighboring spines are constantly exchanging individual molecules. Thus we predict the distribution of PSD-95 cluster sizes that determine the size of the synapse and thus the synaptic strength. Finally, we show that in the model non-equilibrium inter-spine dynamics of PSD-95 molecules can provide the basis for locally controlled synaptic plasticity through activity-dependent ubiquitinization of PSD-95 molecules.

Striatal cellular properties conserved from lampreys to mammals

The striatum of the lamprey, the first vertebrate group to appear in evolution, shows striking similarities to that of mammals with respect to histochemical markers, afferent and efferent projections and the effect of dopamine depletion, which leads to hypokinetic motor symptoms. The cellular properties of lamprey striatal neurons were studied here using patch-clamp recordings in acute striatal slices. Sixty-five per cent of recorded neurons were characterised by a prominent inward rectification due to a K+ conductance of the Kir type. They had a ramping response with a long delay to the first action potential due to activation of a low-voltage-activated A-type K+ current. Many such inwardly rectifying neurons (IRNs) had a hyperpolarised resting membrane potential and some had spiny dendrites. The remaining 35% of the neurons (non-IRNs) represent a heterogeneous group, including some with characteristics similar to the fast-spiking interneuron of the mammalian striatum. They showed short-lasting, large after hyperpolarisations (AHPs) and discharged action potentials at high frequency. None of the recorded neurons were spontaneously active but they received GABAergic and glutamatergic synaptic input. The fact that most lamprey striatal neurons display inward rectification indicates that this is a conserved characteristic of striatal neurons throughout vertebrate phylogeny. This is a cellular property of critical importance for the operations of the striatum in mammals.

Fractional Cable Equation Models for Anomalous Electrodiffusion in Nerve Cells: Finite Domain Solutions

In recent work we introduced fractional Nernst–Planck equations and related fractional cable equations to model electrodiffusion of ions in nerve cells with anomalous subdiffusion along and across the nerve cells. This work was motivated by many computational and experimental studies showing that anomalous diffusion is ubiquitous in biological systems with binding, crowding, or trapping. For example, recent experiments have shown that anomalous subdiffusion occurs along the axial direction in spiny dendrites due to trapping by the spines. We modeled the subdiffusion in two ways leading to two fractional cable equations and presented fundamental solutions on infinite and semi-infinite domains. Here we present solutions on finite domains for mixed Robin boundary conditions. The finite domain solutions model passive electrotonic properties of spiny dendritic branch segments with ends that are voltage clamped, sealed, or killed. The behavior of the finite domain solutions is similar for both fractional cable equations. With uniform subdiffusion along and across the nerve cells, the solution approaches the standard nonzero steady state, but the approach is slowed by the anomalous subdiffusion. If the subdiffusion is more anomalous along the axial direction, then (boundary conditions permitting) the solution converges to a zero steady state, whereas if the subdiffusion is less anomalous along the axial direction, then the solution approaches a spatially linear steady state. These solutions could be compared with realistic electrophysiological experiments on actual dendrites.

Anomalous transport and nonlinear reactions in spiny dendrites

We present a mesoscopic description of the anomalous transport and reactions of particles in spiny dendrites. As a starting point we use two-state Markovian model with the transition probabilities depending on residence time variable. The main assumption is that the longer a particle survives inside spine, the smaller becomes the transition probability from spine to dendrite. We extend a linear model presented in Fedotov [Phys. Rev. Lett. 101, 218102 (2008)] and derive the nonlinear Master equations for the average densities of particles inside spines and parent dendrite by eliminating residence time variable. We show that the flux of particles between spines and parent dendrite is not local in time and space. In particular the average flux of particles from a population of spines through spines necks into parent dendrite depends on chemical reactions in spines. This memory effect means that one cannot separate the exchange flux of particles and the chemical reactions inside spines. This phenomenon does not exist in the Markovian case. The flux of particles from dendrite to spines is found to depend on the transport process inside dendrite. We show that if the particles inside a dendrite have constant velocity, the mean particle's position <x(t)> increases as t(μ) with μ<1 (anomalous advection). We derive a fractional advection-diffusion equation for the total density of particles.

Two New Implicit Numerical Methods for the Fractional Cable Equation

The cable equation is one of the most fundamental equations for modeling neuronal dynamics. Cable equations with fractional order temporal operators have been introduced to model electrotonic properties of spiny neuronal dendrites. In this paper, we consider the following fractional cable equation involving two fractional temporal derivatives: ∂u(x,t)/∂t=D0t1−γ1(κ(∂2u(x,t)/∂x2))−μ02Dt1−γ2u(x,t)+f(x,t), where 0&lt;γ1, γ2&lt;1, κ&gt;0, and μ02 are constants, and D0t1−γu(x,t) is the Rieman–Liouville fractional partial derivative of order 1−γ. Two new implicit numerical methods with convergence order O(τ+h2) and O(τ2+h2) for the fractional cable equation are proposed, respectively, where τ and h are the time and space step sizes. The stability and convergence of these methods are investigated using the energy method. Finally, numerical results are given to demonstrate the effectiveness of both implicit numerical methods. These techniques can also be applied to solve other types of anomalous subdiffusion problems.

Population based quantification of dendrites: evidence for the lack of microtubule-associate protein 2a,b in Purkinje cell spiny dendrites

The high molecular weight isoforms (a and b) of microtubule-associate protein 2 (MAP2a,b) are widely believed to be specific markers for neuronal somata and dendrites. We analyzed and quantified MAP2a,b stained dendrites of the cerebellar molecular layer using a novel approach that segmented and 3D reconstructed them, and the results have been compared with those obtained by other methods, including single-cell reconstruction and analysis of electron micrographs. Our results show that the molecular layer dendritic volume fraction is lower than in the neocortex (10% compared to neocortical 29%). The low total volume fraction of dendrites in the molecular layer is best explained by the majority of the afferents to the dendrites being from the very densely packed parallel fibers, which allows the dendritic fields of individual neurons to be smaller and more compact than in the cerebral cortex. However, the MAP2a,b dendritic volume fraction is even lower (5.2%) than the total volume fraction of dendrites in the molecular layer (10%). Analysis of the material shows that this difference between the two results is due to the unexpected finding that there were few MAP2a,b stained Purkinje cell spiny dendrites.

Interplay of Palmitoylation and Phosphorylation in the Trafficking and Localization of Phosphodiesterase 10A: Implications for the Treatment of Schizophrenia

Phosphodiesterase 10A (PDE10A) is a striatum-enriched, dual-specific cyclic nucleotide phosphodiesterase that has gained considerable attention as a potential therapeutic target for psychiatric disorders such as schizophrenia. As such, a PDE10A-selective inhibitor compound, MP-10, has recently entered clinical testing. Since little is known about the cellular regulation of PDE10A, we sought to elucidate the mechanisms that govern its subcellular localization in striatal medium spiny neurons. Previous reports suggest that PDE10A is primarily membrane bound and is transported throughout medium spiny neuron axons and dendrites. Moreover, it has been shown in PC12 cells that the localization of the major splice form, PDE10A2, may be regulated by protein kinase A phosphorylation at threonine 16 (Thr-16). Using an antibody that specifically recognizes phosphorylated Thr-16 (pThr-16) of PDE10A2, we provide evidence that phosphorylation at Thr-16 is critical for the regulation of PDE10A subcellular localization in vivo. Furthermore, we demonstrate in primary mouse striatal neuron cultures that PDE10A membrane association and transport throughout dendritic processes requires palmitoylation of cysteine 11 (Cys-11) of PDE10A2, likely by the palmitoyl acyltransferases DHHC-7 and -19. Finally, we show that Thr-16 phosphorylation regulates PDE10A trafficking and localization by preventing palmitoylation of Cys-11 rather than by interfering with palmitate-lipid interactions. These data support a model whereby PDE10A trafficking and localization can be regulated in response to local fluctuations in cAMP levels. Given this, we propose that excessive striatal dopamine release, as occurs in schizophrenia, might exert differential effects on the regulation of PDE10A localization in the two striatal output pathways.

Model of inter-spine dynamics of PSD-95 molecules and its application to synaptic plasticity

We present a model of stochastic molecular transport in spiny dendrites. In this model the molecules perform a random walk between the spines that trap the walkers. If the molecules interact with each other inside the spines the trapping time in each spine depends on the number of molecules in the respective trap. The corresponding mathematical problem has non-trivial solutions even in the absence of external disorder due to self-organization phenomenon. We obtain the stationary distributions of the number of walkers in the traps for different kinds of on-site interactions between the walkers. We analyze how birth and death processes of the random walkers affect these distributions. We apply this model to describe the dynamics of the PSD-95 proteins in spiny dendrites. PSD-95 is the most abundant molecule in the post-synaptic density (PSD) located in the spines. It is observed that these molecules have high turnover rates and that neighboring spines are constantly exchanging individual molecules. We propose that the geometry of individual PSD-95 clusters determines the dependence of trapping times on the number of molecules inside the trap and thus can vary from spine to spine. Furthermore, we suggest that activity-dependent reorganization of the PSD-95 cluster can lead to synaptic plasticity in a form of long-term potentiation (LTP). In the model this is achieved by spine specific activity-dependent ubiquitinization of PSD-95 molecules, which transiently reduces the amount of PSD-95 in the spine but change the geometry of the PSD-95 cluster in such a way that self-organization process results in the overall increase of the number of PSD-95 molecules associated with LTP. We also show that such a dynamics of the PSD-95 molecules can set up the conditions for anomalous diffusive transport inside spiny dendrites and predict the distribution of the PSD sizes which has features of both exponential and Poisson distributions.

Functional origins of the vertebrate cerebellum from a sensory processing antecedent

Abstract The structure of the cerebellar cortex is remarkably similar across vertebrate phylogeny. It is well developed in basal jawed fishes, such as sharks and rays with many of the same cell types and organizational features found in other vertebrate groups, including mammals. In particular, the lattice-like organization of cerebellar cortex (with a molecular layer of parallel fibres, interneurons, spiny Purkinje cell dendrites, and climbing fires) is a common defining characteristic. In addition to the cerebellar cortex, fishes and aquatic amphibians have a variety of cerebellum-like structures in the dorso-lateral wall of the hindbrain. These structures are adjacent to, and in part, contiguous with, the cerebellum. They derive their cerebellum-like name from the presence of a molecular layer of parallel fibers and inhibitory interneurons, which has striking organizational similarities to the molecular layer of the cerebellar cortex. However, these structures also have characteristics which differ from the cerebellum. For example, cerebellum-like structures do not have climbing fibres, and they are clearly sensory. They receive direct afferent input from peripheral sensory receptors and relay their outputs to midbrain sensory areas. As a consequence of this close sensory association, and the ability to characterise their signal processing in a behaviourally relevant context, good progress has been made in determining the fundamental processing algorithm in cerebellar-like structures. In particular, we have come to understand the contribution to signal processing made by the molecular layer, which provides an adaptive filter to cancel self-generated noise in electrosensory and lateral line systems. Given the fundamental similarities of the molecular layer across these structures, coupled with evidence that cerebellum-like structures may have been the evolutionary antecedent of the cerebellum, we address the question: do both share the same functional algorithm?

Juxtacellular labeling of tonically active neurons and phasically active neurons in the rat striatum

Tonically active neurons (TANs) and phasically active neurons (PANs) are widely believed to be the cholinergic interneurons and GABAergic projection neurons, respectively, in the striatum based on in vivo intracellular recordings coupled with morphological examinations of anesthetized rats, and on histochemical, electrophysiological, and labeling studies of in vitro slice preparations. TANs of alert behaving animals exhibit prolonged pause responses to behaviorally significant events. PANs, on the other hand, are mostly inactive when subjects are quiet and not performing any actions, but exhibit burst discharges in response to external stimuli and/or voluntary actions. Several other types of interneurons have also been identified in the striatum, such as parvalbumin-containing GABAergic interneurons (fast-spiking cells), somatostatin-containing interneurons, and calretinin-containing interneurons. To identify the neurochemical and morphological characteristics of TANs and PANs in a more direct manner, we conducted juxtacellular labeling, combining electrophysiology with immunohistochemistry and morphology in anesthetized rats. All of the juxtacellularly labeled TANs ( n=3) among those recorded ( n=10) were ChAT-positive and had large cell somata with aspiny dendrites. Thus, although our observations are based on a limited number of neurons, our findings provide the most convincing evidence to date that TANs in the striatum are cholinergic neurons. We also found that the majority of PANs are GABA-immunoreactive (46 of 48 tested) and approximately two-thirds had spiny dendrites (30 of 48 tested), indicating that the majority are medium-sized, spiny, GABAergic projection neurons, consistent with general beliefs. Conversely, the remaining one-third of PANs had aspiny dendrites ( n=18), indicating that they were interneurons. Therefore, the present study reveals that TANs are cholinergic neurons and that the majority of PANs are medium-sized, spiny, GABAergic projection neurons, while a smaller number are GABAergic interneurons.

Rapid time course of action potentials in spines and remote dendrites of mouse visual cortex neurons

Axonally initiated action potentials back-propagate into spiny dendrites of central mammalian neurons and thereby regulate plasticity at excitatory synapses on individual spines as well as linear and supralinear integration of synaptic inputs along dendritic branches. Thus, the electrical behaviour of individual dendritic spines and terminal dendritic branches is critical for the integrative function of nerve cells. The actual dynamics of action potentials in spines and terminal branches, however, are not entirely clear, mostly because electrode recording from such small structures is not feasible. Additionally, the available membrane potential imaging techniques are limited in their sensitivity and require substantial signal averaging for the detection of electrical events at the spatial scale of individual spines. We made a critical improvement in the voltage-sensitive dye imaging technique to achieve multisite recordings of backpropagating action potentials from individual dendritic spines at a high frame rate. With this approach, we obtained direct evidence that in layer 5 pyramidal neurons from the visual cortex of juvenile mice, the rapid time course of somatic action potentials is preserved throughout all cellular compartments, including dendritic spines and terminal branches of basal and apical dendrites. The rapid time course of the action potential in spines may be a critical determinant for the precise regulation of spike timing-dependent synaptic plasticity within a narrow time window.

Model of synaptic plasticity based on self-organization of PSD-95 molecules in spiny dendrites.

Model of synaptic plasticity based on self-organization of PSD-95 molecules in spiny dendrites.