14 research outputs found
Dendritic Spine Shape Analysis: A Clustering Perspective
Functional properties of neurons are strongly coupled with their morphology.
Changes in neuronal activity alter morphological characteristics of dendritic
spines. First step towards understanding the structure-function relationship is
to group spines into main spine classes reported in the literature. Shape
analysis of dendritic spines can help neuroscientists understand the underlying
relationships. Due to unavailability of reliable automated tools, this analysis
is currently performed manually which is a time-intensive and subjective task.
Several studies on spine shape classification have been reported in the
literature, however, there is an on-going debate on whether distinct spine
shape classes exist or whether spines should be modeled through a continuum of
shape variations. Another challenge is the subjectivity and bias that is
introduced due to the supervised nature of classification approaches. In this
paper, we aim to address these issues by presenting a clustering perspective.
In this context, clustering may serve both confirmation of known patterns and
discovery of new ones. We perform cluster analysis on two-photon microscopic
images of spines using morphological, shape, and appearance based features and
gain insights into the spine shape analysis problem. We use histogram of
oriented gradients (HOG), disjunctive normal shape models (DNSM), morphological
features, and intensity profile based features for cluster analysis. We use
x-means to perform cluster analysis that selects the number of clusters
automatically using the Bayesian information criterion (BIC). For all features,
this analysis produces 4 clusters and we observe the formation of at least one
cluster consisting of spines which are difficult to be assigned to a known
class. This observation supports the argument of intermediate shape types.Comment: Accepted for BioImageComputing workshop at ECCV 201
Investigating Sub-Spine Actin Dynamics in Rat Hippocampal Neurons with Super-Resolution Optical Imaging
Morphological changes in dendritic spines represent an important mechanism for synaptic plasticity which is postulated to underlie the vital cognitive phenomena of learning and memory. These morphological changes are driven by the dynamic actin cytoskeleton that is present in dendritic spines. The study of actin dynamics in these spines traditionally has been hindered by the small size of the spine. In this study, we utilize a photo-activation localization microscopy (PALM)βbased single-molecule tracking technique to analyze F-actin movements with βΌ30-nm resolution in cultured hippocampal neurons. We were able to observe the kinematic (physical motion of actin filaments, i.e., retrograde flow) and kinetic (F-actin turn-over) dynamics of F-actin at the single-filament level in dendritic spines. We found that F-actin in dendritic spines exhibits highly heterogeneous kinematic dynamics at the individual filament level, with simultaneous actin flows in both retrograde and anterograde directions. At the ensemble level, movements of filaments integrate into a net retrograde flow of βΌ138 nm/min. These results suggest a weakly polarized F-actin network that consists of mostly short filaments in dendritic spines
Spine neck plasticity regulates compartmentalization of synapses
Dendritic spines have been proposed to transform synaptic signals through chemical and electrical compartmentalization. However, the quantitative contribution of spine morphology to synapse compartmentalization and its dynamic regulation are still poorly understood. We used time-lapse super-resolution stimulated emission depletion (STED) imaging in combination with fluorescence recovery after photobleaching (FRAP) measurements, two-photon glutamate uncaging, electrophysiology and simulations to investigate the dynamic link between nanoscale anatomy and compartmentalization in live spines of CA1 neurons in mouse brain slices. We report a diversity of spine morphologies that argues against common categorization schemes and establish a close link between compartmentalization and spine morphology, wherein spine neck width is the most critical morphological parameter. We demonstrate that spine necks are plastic structures that become wider and shorter after long-term potentiation. These morphological changes are predicted to lead to a substantial drop in spine head excitatory postsynaptic potential (EPSP) while preserving overall biochemical compartmentalization
Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism
The process of axonal and dendritic development establishes the synaptic circuitry of the central nervous system (CNS) and is the result of interactions between intrinsic molecular factors and the external environment. One growth factor that has a compelling function in neuronal development is the neurotrophin brain-derived neurotrophic factor (BDNF). BDNF participates in axonal and dendritic differentiation during embryonic stages of neuronal development, as well as in the formation and maturation of dendritic spines during postnatal development. Recent studies have also implicated vesicular trafficking of BDNF via secretory vesicles, and both secretory and endosomal trafficking of vesicles containing synaptic proteins, such as neurotransmitter and neurotrophin receptors, in the regulation of axonal and dendritic differentiation, and in dendritic spine morphogenesis. Several genes that are either mutated or deregulated in neurodevelopmental disorders associated with mental retardation have now been identified, and several mouse models of these disorders have been generated and characterized. Interestingly, abnormalities in dendritic and synaptic structure are consistently observed in human neurodevelopmental disorders associated with mental retardation, and in mouse models of these disorders as well. Abnormalities in dendritic and synaptic differentiation are thought to underlie altered synaptic function and network connectivity, thus contributing to the clinical outcome. Here, we review the roles of BDNF and vesicular trafficking in axonal and dendritic differentiation in the context of dendritic and axonal morphological impairments commonly observed in neurodevelopmental disorders associated with mental retardation