scholarly journals Synaptic diversity naturally arises from neural decoding of heterogeneous populations

2021 ◽  
Author(s):  
Jacob L. Yates ◽  
Benjamin Scholl
Keyword(s):  
Dendritic Spines ◽  
Cortical Neurons ◽  
In Silico ◽  
Excitatory Synapses ◽  
Neural Decoding ◽  
Functional Heterogeneity ◽  
Synaptic Inputs ◽  
Population Codes ◽  
Optimal Decoding

Abstract The synaptic inputs to single cortical neurons exhibit substantial diversity in their sensory-driven activity. What this diversity reflects is unclear, and appears counter-productive in generating selective somatic responses to specific stimuli. We propose that synaptic diversity arises because neurons decode information from upstream populations. Focusing on a single sensory variable, orientation, we construct a probabilistic decoder that estimates the stimulus orientation from the responses of a realistic, hypothetical input population of neurons. We provide a straightforward mapping from the decoder weights to real excitatory synapses, and find that optimal decoding requires diverse input weights. Analytically derived weights exhibit diversity whenever upstream input populations consist of noisy, correlated, and heterogeneous neurons, as is typically found in vivo. In fact, in silico weight diversity was necessary to accurately decode orientation and matched the functional heterogeneity of dendritic spines imaged in vivo. Our results indicate that synaptic diversity is a necessary component of information transmission and reframes studies of connectivity through the lens of probabilistic population codes. These results suggest that the mapping from synaptic inputs to somatic selectivity may not be directly interpretable without considering input covariance and highlights the importance of population codes in pursuit of the cortical connectome.

scholarly journals Cortical synaptic diversity naturally arises with heterogeneous neural populations

2020 ◽  
Author(s):  
Jacob L. Yates ◽  
Benjamin Scholl
Keyword(s):  
Functional Diversity ◽  
Dendritic Spines ◽  
Cortical Neurons ◽  
Coding Theory ◽  
Population Coding ◽  
Functional Heterogeneity ◽  
Noisy Input ◽  
Neural Populations ◽  
Extract Information

AbstractSynaptic inputs onto single cortical neurons in vivo exhibit substantial functional diversity with respect to sensory-driven activity. However, it is unclear what this diversity reflects, appearing counter-productive in generating tuned responses to specific stimuli. We propose that functional diversity naturally arises if neurons extract information encoded from noisy input populations. Focusing on a single sensory variable, orientation, we construct a probabilistic decoder that estimates orientation from the responses of a realistic hypothetical input population of neurons. Analytically derived weights exhibit diversity when input populations consist of noisy, correlated, and heterogeneous neurons. Weight diversity was necessary to accurately decode orientation. Further, in silico weight diversity matched the functional heterogeneity of dendritic spines imaged in vivo. This suggests that synaptic diversity is expected when information is extracted from realistic input populations, highlighting the importance of studying weighting structures in population coding theory and consideration in pursuits of the cortical connectome.

scholarly journals Dopamine modulates the integrity of the perisynaptic extracellular matrix at excitatory synapses

2019 ◽  
Author(s):  
Jessica Mitlöhner ◽  
Rahul Kaushik ◽  
Hartmut Niekisch ◽  
Armand Blondiaux ◽  
Christine E. Gee ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cortical Neurons ◽  
Receptor Activation ◽  
Synaptic Activity ◽  
Excitatory Synapses ◽  
Intracellular Calcium Signaling ◽  
Rat Cortical Neurons ◽  
Synaptic Receptors

SummaryIn the brain, Hebbian-type and homeostatic forms of plasticity are affected by neuromodulators like dopamine (DA). Modifications of the perisynaptic extracellular matrix (ECM), controlling functions and mobility of synaptic receptors as well as diffusion of transmitters and neuromodulators in the extracellular space, are crucial for the manifestation of plasticity. Mechanistic links between synaptic activation and ECM modifications are largely unknown. Here, we report that neuromodulation via D1-type DA receptors can induce targeted ECM proteolysis specifically at excitatory synapses of rat cortical neurons via proteases ADAMTS-4 and -5. We show that receptor activation induces increased proteolysis of brevican (BC) and aggrecan, two major constituents of the adult ECM, in vivo and in vitro. ADAMTS immunoreactivity is detected near synapses, and shRNA-mediated knockdown reduced BC cleavage. We outline a molecular scenario how synaptic activity and neuromodulation are linked to ECM rearrangements via increased cAMP levels, NMDA receptor activation, and intracellular calcium signaling.

scholarly journals Dendritic nonlinearities are tuned for efficient spike-based computations in cortical circuits

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Balázs B Ujfalussy ◽  
Judit K Makara ◽  
Tiago Branco ◽  
Máté Lengyel
Keyword(s):  
Cortical Neurons ◽  
Activity Patterns ◽  
Pyramidal Cells ◽  
Cortical Circuits ◽  
Functional Link ◽  
Synaptic Inputs ◽  
Two Photon ◽  
Highly Nonlinear ◽  
Efficient Integration

Cortical neurons integrate thousands of synaptic inputs in their dendrites in highly nonlinear ways. It is unknown how these dendritic nonlinearities in individual cells contribute to computations at the level of neural circuits. Here, we show that dendritic nonlinearities are critical for the efficient integration of synaptic inputs in circuits performing analog computations with spiking neurons. We developed a theory that formalizes how a neuron's dendritic nonlinearity that is optimal for integrating synaptic inputs depends on the statistics of its presynaptic activity patterns. Based on their in vivo preynaptic population statistics (firing rates, membrane potential fluctuations, and correlations due to ensemble dynamics), our theory accurately predicted the responses of two different types of cortical pyramidal cells to patterned stimulation by two-photon glutamate uncaging. These results reveal a new computational principle underlying dendritic integration in cortical neurons by suggesting a functional link between cellular and systems--level properties of cortical circuits.

scholarly journals Differential vesicular sorting of AMPA and GABAA receptors

2016 ◽  
Vol 113 (7) ◽  
pp. E922-E931 ◽  
Author(s):  
Yi Gu ◽  
Shu-Ling Chiu ◽  
Bian Liu ◽  
Pei-Hsun Wu ◽  
Michael Delannoy ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Ampa Receptors ◽  
Gabaa Receptors ◽  
Molecular Mechanisms ◽  
Inhibitory Synapses ◽  
Excitatory Synapses ◽  
Rab Gtpases ◽  
Mature Neurons

In mature neurons AMPA receptors cluster at excitatory synapses primarily on dendritic spines, whereas GABAA receptors cluster at inhibitory synapses mainly on the soma and dendritic shafts. The molecular mechanisms underlying the precise sorting of these receptors remain unclear. By directly studying the constitutive exocytic vesicles of AMPA and GABAA receptors in vitro and in vivo, we demonstrate that they are initially sorted into different vesicles in the Golgi apparatus and inserted into distinct domains of the plasma membrane. These insertions are dependent on distinct Rab GTPases and SNARE complexes. The insertion of AMPA receptors requires SNAP25–syntaxin1A/B–VAMP2 complexes, whereas insertion of GABAA receptors relies on SNAP23–syntaxin1A/B–VAMP2 complexes. These SNARE complexes affect surface targeting of AMPA or GABAA receptors and synaptic transmission. Our studies reveal vesicular sorting mechanisms controlling the constitutive exocytosis of AMPA and GABAA receptors, which are critical for the regulation of excitatory and inhibitory responses in neurons.

scholarly journals Human cortical pyramidal neurons: From spines to spikes via models

2018 ◽  
Author(s):  
Guy Eyal ◽  
Matthias B. Verhoog ◽  
Guilherme Testa-Silva ◽  
Yair Deitcher ◽  
Ruth Benavides-Piccione ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Temporal Cortex ◽  
Pyramidal Cells ◽  
Physiological Data ◽  
Excitatory Synapses ◽  
Basal Dendrites ◽  
Cortical Pyramidal Neurons ◽  
Dendritic Branches

AbstractWe present the first-ever detailed models of pyramidal cells from human neocortex, including models on their excitatory synapses, dendritic spines, dendritic NMDA- and somatic/axonal- Na+ spikes that provided new insights into signal processing and computational capabilities of these principal cells. Six human layer 2 and layer 3 pyramidal cells (HL2/L3 PCs) were modeled, integrating detailed anatomical and physiological data from both fresh and post mortem tissues from human temporal cortex. The models predicted particularly large AMPA- and NMDA- conductances per synaptic contact (0.88 nS and 1.31nS, respectively) and a steep dependence of the NMDA-conductance on voltage. These estimates were based on intracellular recordings from synaptically-connected HL2/L3 pairs, combined with extra-cellular current injections and use of synaptic blockers. A large dataset of high-resolution reconstructed HL2/L3 dendritic spines provided estimates for the EPSPs at the spine head (12.7 ± 4.6 mV), spine base (9.7 ± 5.0 mV) and soma (0.3 ± 0.1 mV), and for the spine neck resistance (50 – 80 MΩ). Matching the shape and firing pattern of experimental somatic Na+-spikes provided estimates for the density of the somatic/axonal excitable membrane ion channels, predicting that 134 ± 28 simultaneously activated HL2/L3- HL2/L3 synapses are required for generating (with 50% probability) a somatic Na+ spike. Dendritic NMDA spikes were triggered in the model when 20 ± 10 excitatory spinous synapses were simultaneously activated on individual dendritic branches. The particularly large number of basal dendrites in HL2/L3 PCs and the distinctive cable elongation of their terminals imply that ~25 NMDA- spikes could be generated independently and simultaneously in these cells, as compared to ~14 in L2/3 PCs from the rat temporal cortex. These multi-sites nonlinear signals, together with the large (~30,000) excitatory synapses/cell, equip human L2/L3 PCs with enhanced computational capabilities. Our study provides the most comprehensive model of any human neuron to-date demonstrating the biophysical and computational distinctiveness of human cortical neurons.

scholarly journals Cortical neuron response selectivity derives from strength in numbers of synapses

2019 ◽  
Author(s):  
Benjamin Scholl ◽  
Connon I. Thomas ◽  
Melissa A. Ryan ◽  
Naomi Kamasawa ◽  
David Fitzpatrick
Keyword(s):  
Cortical Neuron ◽  
Cortical Neurons ◽  
Spatial Clustering ◽  
Supporting Evidence ◽  
Cortical Circuits ◽  
Synaptic Inputs ◽  
Synaptic Ultrastructure ◽  
Somatic Response ◽  
Neural Selectivity

AbstractSingle neocortical neurons are driven by populations of excitatory inputs, forming the basis of neural selectivity to features of sensory input. Excitatory connections are thought to mature during development through activity-dependent Hebbian plasticity1, whereby similarity between presynaptic and postsynaptic activity selectively strengthens some synapses and weakens others2. Evidence in support of this process ranges from measurements of synaptic ultrastructure to slice and in vivo physiology and imaging studies3,4,5,6,7,8. These corroborating lines of evidence lead to the prediction that a small number of strong synaptic inputs drive neural selectivity, while weak synaptic inputs are less correlated with the functional properties of somatic output and act to modulate activity overall6,7. Supporting evidence from cortical circuits, however, has been limited to measurements of neighboring, connected cell pairs, raising the question of whether this prediction holds for the full profile of synapses converging onto cortical neurons. Here we measure the strengths of functionally characterized excitatory inputs contacting single pyramidal neurons in ferret primary visual cortex (V1) by combining in vivo two-photon synaptic imaging and post hoc electron microscopy (EM). Using EM reconstruction of individual synapses as a metric of strength, we find no evidence that strong synapses play a predominant role in the selectivity of cortical neuron responses to visual stimuli. Instead, selectivity appears to arise from the total number of synapses activated by different stimuli. Moreover, spatial clustering of co-active inputs, thought to amplify synaptic drive, appears reserved for weaker synapses, further enhancing the contribution of the large number of weak synapses to somatic response. Our results challenge the role of Hebbian mechanisms in shaping neuronal selectivity in cortical circuits, and suggest that selectivity reflects the co-activation of large populations of presynaptic neurons with similar properties and a mixture of strengths.

scholarly journals Phosphorylation of CRMP2 by Cdk5 Regulates Dendritic Spine Development of Cortical Neuron in the Mouse Hippocampus

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Xiaohua Jin ◽  
Kodai Sasamoto ◽  
Jun Nagai ◽  
Yuki Yamazaki ◽  
Kenta Saito ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Cortical Neurons ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Brain Functions ◽  
Spine Development ◽  
Mouse Hippocampus

Proper density and morphology of dendritic spines are important for higher brain functions such as learning and memory. However, our knowledge about molecular mechanisms that regulate the　development and maintenance of dendritic spines is limited. We recently reported that cyclin-dependent kinase 5 (Cdk5) is required for the development and maintenance of dendritic spines of cortical neurons in the mouse brain. Previousin vitrostudies have suggested the involvement of Cdk5 substrates in the formation of dendritic spines; however, their role in spine development has not been testedin vivo. Here, we demonstrate that Cdk5 phosphorylates collapsin response mediator protein 2 (CRMP2) in the dendritic spines of cultured hippocampal neurons andin vivoin the mouse brain. When we eliminated CRMP2 phosphorylation inCRMP2KI/KImice, the densities of dendritic spines significantly decreased in hippocampal CA1 pyramidal neurons in the mouse brain. These results indicate that phosphorylation of CRMP2 by Cdk5 is important for dendritic spine development in cortical neurons in the mouse hippocampus.

scholarly journals Stable but not rigid: Chronic in vivo STED nanoscopy reveals extensive remodeling of spines, indicating multiple drivers of plasticity

2021 ◽  
Vol 7 (24) ◽  
pp. eabf2806
Author(s):  
Heinz Steffens ◽  
Alexander C. Mott ◽  
Siyuan Li ◽  
Waja Wegner ◽  
Pavel Švehla ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Excitatory Synapses ◽  
Memory Locus ◽  
Length Width ◽  
Highly Correlated ◽  
High Degree ◽  
Distinct Features

Excitatory synapses on dendritic spines of pyramidal neurons are considered a central memory locus. To foster both continuous adaption and the storage of long-term information, spines need to be plastic and stable at the same time. Here, we advanced in vivo STED nanoscopy to superresolve distinct features of spines (head size and neck length/width) in mouse neocortex for up to 1 month. While LTP-dependent changes predict highly correlated modifications of spine geometry, we find both, uncorrelated and correlated dynamics, indicating multiple independent drivers of spine remodeling. The magnitude of this remodeling suggests substantial fluctuations in synaptic strength. Despite this high degree of volatility, all spine features exhibit persistent components that are maintained over long periods of time. Furthermore, chronic nanoscopy uncovers structural alterations in the cortex of a mouse model of neurodegeneration. Thus, at the nanoscale, stable dendritic spines exhibit a delicate balance of stability and volatility.

scholarly journals Calsyntenin-3 directly interacts with neurexins to orchestrate excitatory synapse development in the hippocampus

2020 ◽  
Author(s):  
Hyeonho Kim ◽  
Dongwook Kim ◽  
Jinhu Kim ◽  
Hee-Yoon Lee ◽  
Dongseok Park ◽  
...  
Keyword(s):  
Neural Circuits ◽  
Conditional Knockout ◽  
Excitatory Synapse ◽  
Stratum Radiatum ◽  
Excitatory Synapses ◽  
Synapse Development ◽  
Ca1 Neurons ◽  
Synaptic Inputs ◽  
Presynaptic Differentiation

AbstractCalsyntenin-3 (Clstn3) is a postsynaptic adhesion molecule that induces presynaptic differentiation via presynaptic neurexins (Nrxns), but whether Nrxns directly bind to Clstn3 has been a matter of debate. Here, we show that β-Nrxns directly interact via their LNS domain with Clstn3 and Clstn3 cadherin domains. Expression of splice site 4 (SS4) insert-positive β-Nrxn variants, but not insert-negative variants, reversed the impaired Clstn3 synaptogenic activity observed in Nrxn-deficient neurons. Consistently, Clstn3 selectively formed complexes with SS4-positive Nrxns in vivo. Neuron-specific Clstn3 deletion caused significant reductions in number of excitatory synaptic inputs, and moderate impairment of light-induced anxiety-like behaviors in mice. Moreover, expression of Clstn3 cadherin domains in CA1 neurons of Clstn3 conditional knockout mice rescued structural deficits in excitatory synapses, especially within the stratum radiatum layer. Collectively, our results suggest that Clstn3 links to SS4-positive Nrxns to induce presynaptic differentiation and orchestrate excitatory synapse development in specific hippocampal neural circuits.

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