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Biophysical Journal Nov 2017Dendritic spines are protrusions along neuronal dendrites that harbor the majority of excitatory postsynapses. Their distinct morphology, often featuring a bulbous head...
Dendritic spines are protrusions along neuronal dendrites that harbor the majority of excitatory postsynapses. Their distinct morphology, often featuring a bulbous head and small neck that connects to the dendritic shaft, has been shown to facilitate compartmentalization of electrical and cytoplasmic signaling stimuli elicited at the synapse. The extent to which spine morphology also forms a barrier for membrane-bound diffusion has remained unclear. Recent simulations suggested that especially the diameter of the spine neck plays a limiting role in this process. Here, we examine the connection between spine morphology and membrane-bound diffusion through a combination of photoconversion, live-cell superresolution experiments, and numerical simulations. Local photoconversion was used to obtain the timescale of diffusive equilibration in spines and followed by global sparse photoconversion to determine spine morphologies with nanoscopic resolution. These morphologies were subsequently used to assess the role of morphology on the diffusive equilibration. From the simulations, we could determine a robust relation between the equilibration timescale and a generalized shape factor calculated using both spine neck width and neck length, as well as spine head size. Experimentally, we found that diffusive equilibration was often slower, but rarely faster than predicted from the simulations, indicating that other biological confounders further reduce membrane-bound diffusion in these spines. This shape-dependent membrane-bound diffusion in mature spines may contribute to spine-specific compartmentalization of neurotransmitter receptors and signaling molecules and thereby support long-term plasticity of synaptic contacts.
Topics: Animals; Cell Membrane; Dendritic Spines; Diffusion; Hippocampus; Models, Neurological; Molecular Imaging; Rats
PubMed: 28750887
DOI: 10.1016/j.bpj.2017.06.048 -
Journal of Neuroscience Methods Mar 2017Neuronal morphology and function are highly coupled. In particular, dendritic spine morphology is strongly governed by the incoming neuronal activity. The first step...
BACKGROUND
Neuronal morphology and function are highly coupled. In particular, dendritic spine morphology is strongly governed by the incoming neuronal activity. The first step towards understanding the structure-function relationships is to classify spine shapes into the main spine types suggested in the literature. Due to the lack of reliable automated analysis tools, classification is mostly performed manually, which is a time-intensive task and prone to subjectivity.
NEW METHOD
We propose an automated method to classify dendritic spines using shape and appearance features based on challenging two-photon laser scanning microscopy (2PLSM) data. Disjunctive Normal Shape Models (DNSM) is a recently proposed parametric shape representation. We perform segmentation of spine images by applying DNSM and use the resulting representation as shape features. Furthermore, we use Histogram of oriented gradients (HOG) to extract appearance features. In this context, we propose a kernel density estimation (KDE) based framework for dendritic spine classification, which uses these shape and appearance features.
RESULTS
Our shape and appearance features based approach combined with Neural Network (NN) correctly classifies 87.06% of spines on a dataset of 456 spines.
COMPARISON WITH EXISTING METHODS
Our proposed method outperforms standard morphological feature based approaches. Our KDE based framework also enables neuroscientists to analyze the separability of spine shape classes in the likelihood ratio space, which leads to further insights about nature of the spine shape analysis problem.
CONCLUSIONS
Results validate that performance of our proposed approach is comparable to a human expert. It also enable neuroscientists to study shape statistics in the likelihood ratio space.
Topics: Animals; Data Interpretation, Statistical; Dendritic Spines; Hippocampus; Imaging, Three-Dimensional; Machine Learning; Mice; Microscopy, Confocal; Pattern Recognition, Automated; Tissue Culture Techniques
PubMed: 27998713
DOI: 10.1016/j.jneumeth.2016.12.006 -
ACS Chemical Neuroscience May 2023Quantitative methods for assessing neural anatomy have rapidly evolved in neuroscience and provide important insights into brain health and function. However, as new... (Review)
Review
Quantitative methods for assessing neural anatomy have rapidly evolved in neuroscience and provide important insights into brain health and function. However, as new techniques develop, it is not always clear when and how each may be used to answer specific scientific questions posed. Dendritic spines, which are often indicative of synapse formation and neural plasticity, have been implicated across many brain regions in neurodevelopmental disorders as a marker for neural changes reflecting neural dysfunction or alterations. In this Perspective we highlight several techniques for staining, imaging, and quantifying dendritic spines as well as provide a framework for avoiding potential issues related to pseudoreplication. This framework illustrates how others may apply the most rigorous approaches. We consider the cost-benefit analysis of the varied techniques, recognizing that the most sophisticated equipment may not always be necessary for answering some research questions. Together, we hope this piece will help researchers determine the best strategy toward using the ever-growing number of techniques available to determine neural changes underlying dendritic spine morphology in health and neurodevelopmental disorders.
Topics: Humans; Dendritic Spines; Neurodevelopmental Disorders; Neuronal Plasticity; Brain
PubMed: 37070364
DOI: 10.1021/acschemneuro.3c00062 -
Neural Plasticity 2016The asymmetric distribution of various proteins and RNAs is essential for all stages of animal development, and establishment and maintenance of this cellular polarity... (Review)
Review
The asymmetric distribution of various proteins and RNAs is essential for all stages of animal development, and establishment and maintenance of this cellular polarity are regulated by a group of conserved polarity determinants. Studies over the last 10 years highlight important functions for polarity proteins, including apical-basal polarity and planar cell polarity regulators, in dendritic spine development and plasticity. Remarkably, many of the conserved polarity machineries function in similar manners in the context of spine development as they do in epithelial morphogenesis. Interestingly, some polarity proteins also utilize neuronal-specific mechanisms. Although many questions remain unanswered in our understanding of how polarity proteins regulate spine development and plasticity, current and future research will undoubtedly shed more light on how this conserved group of proteins orchestrates different pathways to shape the neuronal circuitry.
Topics: Animals; Cell Polarity; Dendritic Spines; Humans; Neurogenesis; Neuronal Plasticity; Neurons
PubMed: 26839714
DOI: 10.1155/2016/3145019 -
PloS One 2023Proteins from the NANOS family are conserved translational repressors with a well-known role in gonad development in both vertebrates and invertebrates. In addition,...
Proteins from the NANOS family are conserved translational repressors with a well-known role in gonad development in both vertebrates and invertebrates. In addition, Drosophila Nanos controls neuron maturation and function, and rodent Nanos1 affects cortical neuron differentiation. Here we show that rat Nanos1 is expressed in hippocampal neurons and that the siRNA-mediated knockdown of Nanos1 impairs synaptogenesis. We found that both dendritic spine size and number were affected by Nanos1 KD. Dendritic spines were smaller and more numerous. Moreover, whereas in control neurons most dendritic PSD95 clusters contact pre-synaptic structures, a larger proportion of PSD95 clusters lacked a synapsin counterpart upon Nanos1 loss-of-function. Finally, Nanos1 KD impaired the induction of ARC typically triggered by neuron depolarization. These results expand our knowledge on the role of NANOS1 in CNS development and suggest that RNA regulation by NANOS1 governs hippocampal synaptogenesis.
Topics: Animals; Rats; RNA; Hippocampus; RNA-Binding Proteins; Dendritic Spines
PubMed: 37058523
DOI: 10.1371/journal.pone.0284589 -
Behavioural Brain Research May 2021In this study, apical dendritic spine density of neurons in hippocampal, amygdalar and prefrontal cortical areas was compared in rats that were repeatedly winning or...
In this study, apical dendritic spine density of neurons in hippocampal, amygdalar and prefrontal cortical areas was compared in rats that were repeatedly winning or losing social conflicts. Territorial male wild-type Groningen (WTG) rats were allowed multiple daily attacks (>20 times) on intruder males in the resident-intruder paradigm. Frequent winning experiences are known to facilitate uncontrolled aggressive behavior reflected in aggressive attacks on anesthetized males which was also observed in the winners in this study. Both winners and losers were socially housed during the experiments; winners with females to stimulate territorial behavior, and losers with two other losing male rats. Twenty-four hours after the last social encounter, brains from experienced residential winners and repeatedly defeated intruder rats were collected and neuronal morphology in selected brain regions was studied via Golgi-Cox staining. Results indicate that spine density in the apical dendrites of the hippocampal CA1 reduced similarly in both winners and losers. In addition, winners showed increased spine densities at the proximal segments (20-30 μm) of the basolateral amygdala neurons and losers tended to show a decreased spine density at the more proximal segments of the infralimbic region of prefrontal cortex neurons. No effect of winning and losing was observed in the medial amygdala. The atrophic effect of repeated defeats in hippocampal and prefrontal regions was anticipated despite the fact that social housing of the repeatedly losing intruder males may have played a protective role. The reduction of hippocampal spine density in the winners seems surprising but supports previous findings in hierarchical dominant males in rat colonies. The dominants showed even greater shrinkage of the apical dendritic arbors of hippocampal CA3 pyramidal neurons compared to the stressed subordinates.
Topics: Animals; Basolateral Nuclear Complex; Behavior, Animal; CA1 Region, Hippocampal; Competitive Behavior; Dendritic Spines; Male; Neuronal Plasticity; Prefrontal Cortex; Pyramidal Cells; Rats; Social Dominance
PubMed: 33727049
DOI: 10.1016/j.bbr.2021.113243 -
The Journal of Comparative Neurology Apr 2021Lafora disease (LD) is a genetic and fatal form of neurodegenerative disorder characterized by myoclonic epilepsy and cognitive deficits. LD is caused by...
Lafora disease (LD) is a genetic and fatal form of neurodegenerative disorder characterized by myoclonic epilepsy and cognitive deficits. LD is caused by loss-of-function mutations in the EPM2A or the NHLRC1 gene. A major hallmark of LD is the presence of abnormal glycogen aggregates in neurons and other tissues. Functional studies on the genes have, therefore, mostly focused on glycogen metabolism. The physiological basis of cognitive deficits in LD is thus largely unexplored. Alterations in dendritic spine morphology are known in neurodevelopmental and neuropsychiatric disorders. We, therefore, analyzed the dendritic spine morphologies in pyramidal neurons of the hippocampal and Cortical layer V of the Epm2a or Nhlrc1 knockout mice brain. We found a significant increase in the density, length, and reduction in the width of the dendritic spines in Postnatal day 21 to 12-month-old LD animals. Similar observations were made in the primary cultures of neurons derived from the hippocampi of the embryonic brain, suggesting that the aberrant spine phenotype could be a developmental defect in LD. We also looked at the cognitive and behavioral deficits as a possible readout of the spine abnormalities. The LD animals exhibited hyperactivity, reduced anxiety-like behavior, and deficits in the spatial and nonspatial memory. Such abnormalities were seen in the younger (1-2 months) as well as the older (7-8 months) age groups. Taken together, our results suggest that the dendritic spine abnormalities are primary developmental defects in the LD model and these defects might underlie some of the symptoms, including cognitive deficits, in LD.
Topics: Animals; Cells, Cultured; Cerebral Cortex; Cognitive Dysfunction; Dendritic Spines; Female; Hippocampus; Lafora Disease; Male; Memory; Mice; Mice, Knockout; Pregnancy; Protein Tyrosine Phosphatases, Non-Receptor; Ubiquitin-Protein Ligases
PubMed: 32785985
DOI: 10.1002/cne.25006 -
Nature Communications Jan 2018Modeling studies suggest that clustered structural plasticity of dendritic spines is an efficient mechanism of information storage in cortical circuits. However, why new...
Modeling studies suggest that clustered structural plasticity of dendritic spines is an efficient mechanism of information storage in cortical circuits. However, why new clustered spines occur in specific locations and how their formation relates to learning and memory (L&M) remain unclear. Using in vivo two-photon microscopy, we track spine dynamics in retrosplenial cortex before, during, and after two forms of episodic-like learning and find that spine turnover before learning predicts future L&M performance, as well as the localization and rates of spine clustering. Consistent with the idea that these measures are causally related, a genetic manipulation that enhances spine turnover also enhances both L&M and spine clustering. Biophysically inspired modeling suggests turnover increases clustering, network sparsity, and memory capacity. These results support a hotspot model where spine turnover is the driver for localization of clustered spine formation, which serves to modulate network function, thus influencing storage capacity and L&M.
Topics: Animals; Cerebral Cortex; Conditioning, Psychological; Dendritic Spines; Fear; Female; Intravital Microscopy; Learning; Male; Memory; Mice; Neuronal Plasticity; Spatial Memory
PubMed: 29379017
DOI: 10.1038/s41467-017-02751-2 -
Biochimica Et Biophysica Acta Oct 2014The development of dendritic spines with specific geometry and membrane composition is critical for proper synaptic function. Specific spine membrane architecture,... (Review)
Review
The development of dendritic spines with specific geometry and membrane composition is critical for proper synaptic function. Specific spine membrane architecture, sub-spine microdomains and spine head and neck geometry allow for well-coordinated and compartmentalized signaling, disruption of which could lead to various neurological diseases. Research from neuronal cell culture, brain slices and direct in vivo imaging indicates that dendritic spine development is a dynamic process which includes transition from small dendritic filopodia through a series of structural refinements to elaborate spines of various morphologies. Despite intensive research, the precise coordination of this morphological transition, the changes in molecular composition, and the relation of spines of various morphologies to function remain a central enigma in the development of functional neuronal circuits. Here, we review research so far and aim to provide insight into the key events that drive structural change during transition from immature filopodia to fully functional spines and the relevance of spine geometry to function.
Topics: Animals; Dendritic Spines; Humans; Membrane Microdomains; Nervous System Diseases; Pseudopodia; Signal Transduction
PubMed: 24915021
DOI: 10.1016/j.bbamem.2014.06.002 -
Cells Dec 2021Dendritic spines are small, thin, hair-like protrusions found on the dendritic processes of neurons. They serve as independent compartments providing large amplitudes of... (Review)
Review
Dendritic spines are small, thin, hair-like protrusions found on the dendritic processes of neurons. They serve as independent compartments providing large amplitudes of Ca signals to achieve synaptic plasticity, provide sites for newer synapses, facilitate learning and memory. One of the common and severe complication of neurodegenerative disease is cognitive impairment, which is said to be closely associated with spine pathologies viz., decreased in spine density, spine length, spine volume, spine size etc. Many treatments targeting neurological diseases have shown to improve the spine structure and distribution. However, concise data on the various modulators of dendritic spines are imperative and a need of the hour. Hence, in this review we made an attempt to consolidate the effects of various pharmacological (cholinergic, glutamatergic, GABAergic, serotonergic, adrenergic, and dopaminergic agents) and non-pharmacological modulators (dietary interventions, enriched environment, yoga and meditation) on dendritic spines structure and functions. These data suggest that both the pharmacological and non-pharmacological modulators produced significant improvement in dendritic spine structure and functions and in turn reversing the pathologies underlying neurodegeneration. Intriguingly, the non-pharmacological approaches have shown to improve intellectual performances both in preclinical and clinical platforms, but still more technology-based evidence needs to be studied. Thus, we conclude that a combination of pharmacological and non-pharmacological intervention may restore cognitive performance synergistically via improving dendritic spine number and functions in various neurological disorders.
Topics: Cholinergic Agents; Cognitive Dysfunction; Dendritic Spines; Diet; Excitatory Amino Acid Agents; GABA Agents; Humans; Meditation; Neurodegenerative Diseases; Neurons; Synapses; Yoga
PubMed: 34943913
DOI: 10.3390/cells10123405