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

Regional Diversity in the Postsynaptic Proteome of the Mouse Brain

The proteome of the postsynaptic terminal of excitatory synapses comprises over one thousand proteins in vertebrate species and plays a central role in behavior and brain disease. The brain is organized into anatomically distinct regions and whether the synapse proteome differs across these regions is poorly understood. Postsynaptic proteomes were isolated from seven forebrain and hindbrain regions in mice and their composition determined using proteomic mass spectrometry. Seventy-four percent of proteins showed differential expression and each region displayed a unique compositional signature. These signatures correlated with the anatomical divisions of the brain and their embryological origins. Biochemical pathways controlling plasticity and disease, protein interaction networks and individual proteins involved with cognition all showed differential regional expression. Combining proteomic and connectomic data shows that interconnected regions have specific proteome signatures. Diversity in synapse proteome composition is key feature of mouse and human brain structure

A model for generating synthetic dendrites of cortical neurons

One of the main challenges in neuroscience is to define the detailed structural design of the nervous system. This challenge is one of the first steps towards understanding how neural circuits contribute to the functional organization of the nervous system. In the cerebral cortex pyramidal neurons are key elements in brain function as they represent the most abundant cortical neuronal type and the main source of cortical excitatory synapses. Therefore, many researchers are interested in the analysis of the microanatomy of pyramidal cells since it constitutes an excellent tool for better understanding cortical processing of information. Computational models of neuronal networks based on real cortical circuits have become useful tools for studying certain aspects of the functional organization of the neocortex. Neuronal morphologies (morphological models) represent key features in these functional models. For these purposes, synthetic or virtual dendritic trees can be generated through a morphological model of a given neuronal type based on real morphometric parameters obtained from intracellularly-filled single neurons. This paper presents a new method to construct virtual dendrites by means of sampling a branching model that represents the dendritic morphology. This method has been contrasted using complete basal dendrites from 374 layer II/III pyramidal neurons of the mouse neocortex

Slow-wave activity in the S1HL cortex is contributed by different layer-specific field potential sources during development

Spontaneous correlated activity in cortical columns is criticalfor postnatal circuit refinement.We used spatial discriminationtechniques to explore the late maturation of synaptic pathways through the laminar distribution of the field potential (FP) generators underlying spontaneous and evoked activities ofthe S1HL cortex in juvenile (P14 –P16) and adult anesthetized rats. Juveniles exhibit an intermittent FP pattern resembling Up/Down states in adults, but with much reduced power and different laminar distribution. Whereas FPs in active periods are dominated by a layer VI generator in juveniles, in adults a developing multipart generatortakes over, displaying current sinks in middle layers (III–V). The blockade of excitatory transmission in upper and middle layers of adults recovered the juvenile-like FP profiles. In additiontothe layer VI generator, a gamma-specific generator in supragranular layers wasthe same in both age groups.While searching for dynamical coupling among generators in juveniles we found significant cross-correlation in one-half of the tested pairs, whereas excessive coherence hindered their efficient separation in adults. Also, potentials evoked by tactile and electrical stimuli showed different short-latency dipoles between the two age groups, and the juveniles lacked the characteristic long latency UP state currents in middle layers. In addition, the mean firing rate of neurons was lower in juveniles. Thus, cortical FPs originate from different intracolumnar segments as they become active postnatally. We suggest that although some cortical segments are active early postnatally, a functional sensory-motor control relies on a delayed maturation and network integration of synaptic connections in middle layers

High plasticity of axonal pathology in Alzheimer's disease mouse models

Axonal dystrophies (AxDs) are swollen and tortuous neuronal processes that are associated with extracellular depositions of amyloid beta (Abeta) and have been observed to contribute to synaptic alterations occurring in Alzheimer's disease. Understanding the temporal course of this axonal pathology is of high relevance to comprehend the progression of the disease over time. We performed a long-term in vivo study (up to 210 days of two-photon imaging) with two transgenic mouse models (dE9xGFP-M and APP-PS1xGFP-M). Interestingly, AxDs were formed only in a quarter of GFP-expressing axons near Abeta-plaques, which indicates a selective vulnerability. AxDs, especially those reaching larger sizes, had long lifetimes and appeared as highly plastic structures with large variations in size and shape and axonal sprouting over time. In the case of the APP-PS1 mouse only, the formation of new long axonal segments in dystrophic axons (re-growth phenomenon) was observed. Moreover, new AxDs could appear at the same point of the axon where a previous AxD had been located before disappearance (re-formation phenomenon). In addition, we observed that most AxDs were formed and developed during the imaging period, and numerous AxDs had already disappeared by the end of this time. This work is the first in vivo study analyzing quantitatively the high plasticity of the axonal pathology around Abeta plaques. We hypothesized that a therapeutically early prevention of Abeta plaque formation or their growth might halt disease progression and promote functional axon regeneration and the recovery of neural circuits

High plasticity of axonal pathology in Alzheimer's disease mouse models

Axonal dystrophies (AxDs) are swollen and tortuous neuronal processes that are associated with extracellular depositions of amyloid beta (Abeta) and have been observed to contribute to synaptic alterations occurring in Alzheimer's disease. Understanding the temporal course of this axonal pathology is of high relevance to comprehend the progression of the disease over time. We performed a long-term in vivo study (up to 210 days of two-photon imaging) with two transgenic mouse models (dE9xGFP-M and APP-PS1xGFP-M). Interestingly, AxDs were formed only in a quarter of GFP-expressing axons near Abeta-plaques, which indicates a selective vulnerability. AxDs, especially those reaching larger sizes, had long lifetimes and appeared as highly plastic structures with large variations in size and shape and axonal sprouting over time. In the case of the APP-PS1 mouse only, the formation of new long axonal segments in dystrophic axons (re-growth phenomenon) was observed. Moreover, new AxDs could appear at the same point of the axon where a previous AxD had been located before disappearance (re-formation phenomenon). In addition, we observed that most AxDs were formed and developed during the imaging period, and numerous AxDs had already disappeared by the end of this time. This work is the first in vivo study analyzing quantitatively the high plasticity of the axonal pathology around Abeta plaques. We hypothesized that a therapeutically early prevention of Abeta plaque formation or their growth might halt disease progression and promote functional axon regeneration and the recovery of neural circuits

Subthreshold dynamics of the neural membrane potential driven by stochastic synaptic input

In the cerebral cortex, neurons are subject to a continuous bombardment of synaptic inputs originating from the network's background activity. This leads to ongoing, mostly subthreshold membrane dynamics that depends on the statistics of the background activity and of the synapses made on a neuron. Subthreshold membrane polarization is, in turn, a potent modulator of neural responses. The present paper analyzes the subthreshold dynamics of the neural membrane potential driven by synaptic inputs of stationary statistics. Synaptic inputs are considered in linear interaction. The analysis identifies regimes of input statistics which give rise to stationary, fluctuating, oscillatory, and unstable dynamics. In particular, I show that (i) mere noise inputs can drive the membrane potential into sustained, quasiperiodic oscillations (noise-driven oscillations), in the absence of a stimulus-derived, intraneural, or network pacemaker; (ii) adding hyperpolarizing to depolarizing synaptic input can increase neural activity (hyperpolarization-induced activity), in the absence of hyperpolarization-activated currents

Characterization of the shallow subsurface structure across the Carrascoy Fault System (SE Iberian Peninsula) using P-wave tomography and Multichannel Analysis of Surface Waves

The seismicity in the SE Iberian Peninsula is distributed parallel to the coast in a well-developed strike-slip fracture system known as the Eastern Betic Shear Zone (EBSZ). This work focuses on the characterization of the shallow subsurface structure of the Algezares-Casas Nuevas Fault, within the Carrascoy Fault System of the EBSZ. The Carrascoy Fault borders the Guadalentín Depression to the south, which is a densely populated area with extensive agricultural activity. Therefore, this faults system represents a seismic hazard with significant social and economic implications. We have constructed two velocity-depth models based on P-wave tomography and Multichannel Analysis of Surface Waves (MASW) acquired from seismic reflection data. The resulting velocity models have allowed us to interpret the first ~250m depth and have revealed: i) the thickness of the critical zone; ii) the geometry of the Algezares-Casas Nuevas Fault; iii) the depth of the Messinian/Tortonian contact and iv) the presence of blind thrusts and damage zones under the Guadalentín Depression. Our results have also helped us to estimate an apparent vertical slip rate of 0.66±0.06m/ky for the Algezares-Casas Nuevas Fault since 209.1±6.2ka. Our results provide a methodological and backflow protocol to study the shallow subsurface of active faults, complementing previous geological models based on paleoseismological trenches, and can be used to improve the seismic hazard assessment of tectonically active regions around the world.The authors would like to acknowledge the project INTERGEO (CGL2013-47412-C2-1-P) GEO3BCNCSIC for the data access. Data are public access through SeisDARE (DeFelipe et al., 2021), dataset Martí et al. (2015). The Ministry of Education and Culture of the Republic of Indonesia is thanked for the main author’s Ph.D. scholarship (D3.2/KD.02.01/2019). JA is funded by MICINN (IJC2018-026335-I). I.P. is funded by the Spanish Government and the Universidad de Salamanca (Beatriz Galindo grant BEGAL 18/00090). IDF is funded by a FEDER-Junta de Castilla y León Postdoctoral contract (SA0084P20). We thank the GIPP-GFZ, (Germany) and Lisbon University (Portugal) for the instrumentation provided. Generalitat de Catalunya (AGAUR) grant 2017SGR1022 (GREG); EU (H2020) 871121 (EPOSSP); and EIT-RawMaterias 17024 (SIT4ME). WPeer reviewe

Characterization of the shallow subsurface structure across the Carrascoy Fault System (SE Iberian Peninsula) using P-wave tomography and Multichannel Analysis of Surface Waves

The seismicity in the SE Iberian Peninsula is distributed parallel to the coast in a well-developed strike-slip fracture system known as the Eastern Betic Shear Zone (EBSZ). This work focuses on the characterization of the shallow subsurface structure of the Algezares-Casas Nuevas Fault, within the Carrascoy Fault System of the EBSZ. The Carrascoy Fault borders the Guadalentín Depression to the south, which is a densely populated area with extensive agricultural activity. Therefore, this faults system represents a seismic hazard with significant social and economic implications. We have constructed two velocity-depth models based on P-wave tomography and Multichannel Analysis of Surface Waves (MASW) acquired from seismic reflection data. The resulting velocity models have allowed us to interpret the first ~250m depth and have revealed: i) the thickness of the critical zone; ii) the geometry of the Algezares-Casas Nuevas Fault; iii) the depth of the Messinian/Tortonian contact and iv) the presence of blind thrusts and damage zones under the Guadalentín Depression. Our results have also helped us to estimate an apparent vertical slip rate of 0.66±0.06m/ky for the Algezares-Casas Nuevas Fault since 209.1±6.2ka. Our results provide a methodological and backflow protocol to study the shallow subsurface of active faults, complementing previous geological models based on paleoseismological trenches, and can be used to improve the seismic hazard assessment of tectonically active regions around the world

New insights into the classification and nomenclature of cortical GABAergic interneurons.

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus