scholarly journals Astrocytes refine cortical connectivity at dendritic spines

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
W Christopher Risher ◽  
Sagar Patel ◽  
Il Hwan Kim ◽  
Akiyoshi Uezu ◽  
Srishti Bhagat ◽  
...  

During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines.

Author(s):  
Kristen M. Harris

Dendritic spines are the tiny protrusions that stud the surface of many neurons and they are the location of over 90% of all excitatory synapses that occur in the central nervous system. Their small size and variable shapes has in large part made detailed study of their structure refractory to conventional light microscopy and single section electron microscopy (EM). Yet their widespread occurrence and likely involvement in learning and memory has motivated extensive efforts to obtain quantitative descriptions of spines in both steady state and dynamic conditions. Since the seminal mathematical analyses of D’Arcy Thompson, the power of establishing quantitatively key parameters of structure has become recognized as a foundation of successful biological inquiry. For dendritic spines highly precise determinations of structure and its variation are proving themselves as the kingpin for establishing a valid concept of function. The recent conjunction of high quality information about the structure, function, and theoretical implications of dendritic spines has produced a flurry of new considerations of their role in synaptic transmission.


2020 ◽  
Author(s):  
Georg Hafner ◽  
Julien Guy ◽  
Mirko Witte ◽  
Pavel Truschow ◽  
Alina Rüppel ◽  
...  

Abstract The neocortex is composed of layers. Whether layers constitute an essential framework for the formation of functional circuits is not well understood. We investigated the brain-wide input connectivity of vasoactive intestinal polypeptide (VIP) expressing neurons in the reeler mouse. This mutant is characterized by a migration deficit of cortical neurons so that no layers are formed. Still, neurons retain their properties and reeler mice show little cognitive impairment. We focused on VIP neurons because they are known to receive strong long-range inputs and have a typical laminar bias toward upper layers. In reeler, these neurons are more dispersed across the cortex. We mapped the brain-wide inputs of VIP neurons in barrel cortex of wild-type and reeler mice with rabies virus tracing. Innervation by subcortical inputs was not altered in reeler, in contrast to the cortical circuitry. Numbers of long-range ipsilateral cortical inputs were reduced in reeler, while contralateral inputs were strongly increased. Reeler mice had more callosal projection neurons. Hence, the corpus callosum was larger in reeler as shown by structural imaging. We argue that, in the absence of cortical layers, circuits with subcortical structures are maintained but cortical neurons establish a different network that largely preserves cognitive functions.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Inna V Nechipurenko ◽  
Cristina Berciu ◽  
Piali Sengupta ◽  
Daniela Nicastro

The primary cilium is nucleated by the mother centriole-derived basal body (BB) via as yet poorly characterized mechanisms. BBs have been reported to degenerate following ciliogenesis in the C. elegans embryo, although neither BB architecture nor early ciliogenesis steps have been described in this organism. In a previous study (Doroquez et al., 2014), we described the three-dimensional morphologies of sensory neuron cilia in adult C. elegans hermaphrodites at high resolution. Here, we use serial section electron microscopy and tomography of staged C. elegans embryos to demonstrate that BBs remodel to support ciliogenesis in a subset of sensory neurons. We show that centriolar singlet microtubules are converted into BB doublets which subsequently grow asynchronously to template the ciliary axoneme, visualize degeneration of the centriole core, and define the developmental stage at which the transition zone is established. Our work provides a framework for future investigations into the mechanisms underlying BB remodeling.


2020 ◽  
Author(s):  
Zhikai Liu ◽  
Yukiko Kimura ◽  
Shin-ichi Higashijima ◽  
David G. Hildebrand ◽  
Joshua L. Morgan ◽  
...  

AbstractAs sensory information moves through the brain, higher-order areas exhibit more complex tuning than lower areas. Though models predict this complexity is due to convergent inputs from neurons with diverse response properties, in most vertebrate systems convergence has only been inferred rather than tested directly. Here we measure sensory computations in zebrafish vestibular neurons across multiple axes in vivo. We establish that whole-cell physiological recordings reveal tuning of individual vestibular afferent inputs and their postsynaptic targets. An independent approach, serial section electron microscopy, supports the inferred connectivity. We find that afferents with similar or differing preferred directions converge on central vestibular neurons, conferring more simple or complex tuning, respectively. Our data also resolve a long-standing contradiction between anatomical and physiological analyses by revealing that sensory responses are produced by sparse but powerful inputs from vestibular afferents. Together these results provide a direct, quantifiable demonstration of feedforward input convergence in vivo.


2020 ◽  
Vol 117 (33) ◽  
pp. 20254-20264 ◽  
Author(s):  
Deng Zhang ◽  
Xingjian Yan ◽  
Liang She ◽  
Yunqing Wen ◽  
Mu-ming Poo

Correlated activation of cortical neurons often occurs in the brain and repetitive correlated neuronal firing could cause long-term modifications of synaptic efficacy and intrinsic excitability. We found that repetitive optogenetic activation of neuronal populations in the mouse cortex caused enhancement of optogenetically evoked firing of local coactivated neurons as well as distant cortical neurons in both ipsilateral and contralateral hemispheres. This global enhancement of evoked responses required coactivation of a sufficiently large population of neurons either within one cortical area or distributed in several areas. Enhancement of neuronal firing was saturable after repeated episodes of coactivation, diminished by inhibition ofN-methyl-d-aspartic acid receptors, and accompanied by elevated excitatory postsynaptic potentials, all consistent with activity-induced synaptic potentiation. Chemogenetic inhibition of neuronal activity of the thalamus decreased the enhancement effect, suggesting thalamic involvement. Thus, correlated excitation of large neuronal populations leads to global enhancement of neuronal excitability.


2018 ◽  
Author(s):  
Valentina Baena ◽  
Mark Terasaki

AbstractEach mammalian oocyte is nurtured by its own multi-cellular structure, the ovarian follicle. We used new methods for serial section electron microscopy to examine entire cells and their projections in mouse antral ovarian follicles. It is already known that cumulus cells send towards the oocyte thin cytoplasmic projections called transzonal projections (TZPs), which are crucial for normal oocyte development. We found that most TZPs do not reach the oocyte, and that they often branch and make gap junctions with each other. Furthermore, the connected TZPs are usually contacted on their shaft by oocyte microvilli. Mural granulosa cells were found to possess randomly oriented cytoplasmic projections that are strikingly similar to free-ended TZPs. We propose that granulosa cells use cytoplasmic projections to search for the oocyte, and cumulus cell differentiation results from a contact-mediated paracrine interaction with the oocyte.


2020 ◽  
Author(s):  
Ninna Shuhaibar ◽  
Arthur R. Hand ◽  
Mark Terasaki

AbstractOdontoblast processes are thin cytoplasmic projections that extend from the cell body at the periphery of the pulp toward the dentin-enamel junction. The odontoblast processes function in the secretion and assembly of dentin during development, participate in mechanosensation, and aid in dentin repair in mature teeth. Because they are small and densely arranged, their three-dimensional organization is not well documented. To gain further insight into how odontoblast processes contribute to odontogenesis, we used serial section electron microscopy to examine these processes in the predentin region of mouse molars and incisors. In molars, the odontoblast processes are tubular with a diameter of ~1.8 μm. The odontoblast processes near the incisor tip are similarly shaped, but those midway between the tip and apex are shaped like plates. The plates are radially aligned and longitudinally oriented with respect to the growth axis of the incisor. The thickness of the plates is approximately the same as the diameter of molar odontoblast processes. The plates have an irregular edge; the average ratio of width (midway in the predentin) to thickness is 2.3 on the labial side and 3.6 on the lingual side. The plate geometry seems likely to be related to the continuous growth of the incisor and may provide a clue as to the mechanisms by which the odontoblast processes are involved in tooth development.


2020 ◽  
Author(s):  
Yulia Dembitskaya ◽  
Nikolay Gavrilov ◽  
Igor Kraev ◽  
Maxim Doronin ◽  
Olga Tyurikova ◽  
...  

AbstractThe brain extracellular matrix (ECM) is a proteoglycan complex that occupies the extracellular space between brain cells and regulates brain development, brain wiring, and synaptic plasticity. However, the action of the ECM on synaptic plasticity remains controversial. Here, we employed serial section electron microscopy to show that enzymatic attenuation of ECM with chondroitinase ABC (ChABC) triggers the appearance of new glutamatergic synapses onto thin dendritic spines of CA1 pyramidal neurons. The appearance of new synapses increased the ratio of the field excitatory postsynaptic potential (fEPSP) to presynaptic fiber volley (PrV), suggesting that these new synapses are formed on existing axonal fibers. However, both the mean miniature excitatory postsynaptic current (mEPSC) amplitude and AMPA/NMDA ratio were decreased, suggesting that ECM attenuation increased the proportion of ‘unpotentiated’ synapses. A higher proportion of unpotentiated synapses would be expected to promote long-term potentiation (LTP). Surprisingly, theta-burst induced LTP was suppressed by ChABC treatment. The suppression of LTP was accompanied by decreased excitability of CA1 pyramidal neurons due to the upregulation of small conductance Ca2+-activated K+ (SK) channels. A pharmacological blockade of SK channels restored cell excitability and, expectedly, enhanced LTP above the level of control. This enhancement of LTP was abolished by a blockade of Rho-associated protein kinase (ROCK), which is involved in the maturation of dendritic spines. Thus, ECM attenuation enables the appearance of new synapses in the hippocampus, which is compensated for by a reduction in the excitability of postsynaptic neurons, thereby preventing network overexcitation at the expense of synaptic plasticity.


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