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 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 Navigating the translational roadblock: Towards highly specific and effective all-optical interrogations of neural circuits

2020 ◽  
Author(s):  
Ting Fu ◽  
Isabelle Arnoux ◽  
Jan Döring ◽  
Hirofumi Watari ◽  
Ignas Stasevicius ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Calcium Imaging ◽  
Cortical Neurons ◽  
Activity Patterns ◽  
Detection Algorithm ◽  
Two Photon ◽  
All Optical ◽  
Laser Sources ◽  
Mouse Visual Cortex

AbstractTwo-photon (2-P) all-optical approaches combine in vivo 2-P calcium imaging and 2-P optogenetic modulations and have the potential to build a framework for network-based therapies, e.g. for rebalancing maladaptive activity patterns in preclinical models of neurological disorders. Here, our goal was to tailor these approaches for this purpose: Firstly, we combined in vivo juxtacellular recordings and GCaMP6f-based 2-P calcium imaging in layer II/III of mouse visual cortex to tune our detection algorithm towards a 100 % specific identification of AP-related calcium transients. False-positive-free detection was achieved at a sensitivity of approximately 73 %. To further increase specificity, secondly, we minimized photostimulation artifacts as a potential source for false-positives by using extended-wavelength-spectrum laser sources for optogenetic stimulation of the excitatory opsin C1V1. We achieved artifact-free all-optical experiments performing photostimulations at 1100 nm or higher and simultaneous calcium imaging at 920 nm in mouse visual cortex in vivo. Thirdly, we determined the spectral range for maximizing efficacy of optogenetic control by performing 2-P photostimulations of individual neurons with wavelengths up to 1300 nm. The rate of evoked transients in GCaMP6f/C1V1-co-expressing cortical neurons peaked already at 1100 nm. By refining spike detection and defining 1100 nm as the optimal wavelength for artifact-free and effective stimulations of C1V1 in GCaMP-based all-optical interrogations, we increased the translational value of these approaches, e.g. for the use in preclinical applications of network-based therapies.One Sentence SummaryWe maximize translational relevance of 2-P all-optical physiology by increasing specificity, minimizing artifacts and optimizing stimulation efficacy.

Opposing roles for neurotrophin-3 in targeting and collateral formation of distinct sets of developing cortical neurons

Development ◽  
1999 ◽  
Vol 126 (15) ◽  
pp. 3335-3345
Author(s):  
V. Castellani ◽  
J. Bolz
Keyword(s):  
Cortical Neurons ◽  
Developmental Stages ◽  
Axonal Guidance ◽  
Cortical Circuits ◽  
Axonal Branching ◽  
Guidance Cue ◽  
Neurotrophin 3 ◽  
Cortical Membranes ◽  
Opposing Effects

Neurotrophin-3 and its receptor TrkC are expressed during the development of the mammalian cerebral cortex. To examine whether neurotrophin-3 might play a role in the elaboration of layer-specific cortical circuits, slices of layer 6 and layers 2/3 neurons were cultured in the presence of exogenously applied neurotrophin-3. Results indicate that neurotrophin-3 promotes axonal branching of layer 6 axons, which target neurotrophin-3-expressing layers in vivo, and that it inhibits branching of layers 2/3 axons, which avoid neurotrophin-3-expressing layers. Such opposing effects of neurotrophin-3 on axonal branching were also observed with embryonic cortical neurons, indicating that the response to neurotrophin-3 is specified at early developmental stages, prior to cell migration. In addition to its effects on fiber branching, axonal guidance assays also indicate that neurotrophin-3 is an attractive signal for layer 6 axons and a repellent guidance cue for layers 2/3 axons. Experiments with specific antibodies to neutralize neurotrophin-3 in cortical membranes revealed that endogenous levels of neurotrophin-3 are sufficient to regulate branching and targeting of cortical axons. These opposing effects of neurotrophin-3 on specific populations of axons demonstrate that it could serve as one of the signals for the elaboration of local cortical circuits.

Possible Effects of Depolarizing GABAA Conductance on the Neuronal Input–Output Relationship: A Modeling Study

2005 ◽  
Vol 93 (6) ◽  
pp. 3504-3523 ◽  
Author(s):  
Kenji Morita ◽  
Kunichika Tsumoto ◽  
Kazuyuki Aihara
Keyword(s):  
Firing Rate ◽  
Cortical Neurons ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Resting Potential ◽  
Input Output ◽  
Wide Range ◽  
The Relationship

Recent in vitro experiments revealed that the GABAA reversal potential is about 10 mV higher than the resting potential in mature mammalian neocortical pyramidal cells; thus GABAergic inputs could have facilitatory, rather than inhibitory, effects on action potential generation under certain conditions. However, how the relationship between excitatory input conductances and the output firing rate is modulated by such depolarizing GABAergic inputs under in vivo circumstances has not yet been understood. We examine herewith the input–output relationship in a simple conductance-based model of cortical neurons with the depolarized GABAA reversal potential, and show that a tonic depolarizing GABAergic conductance up to a certain amount does not change the relationship between a tonic glutamatergic driving conductance and the output firing rate, whereas a higher GABAergic conductance prevents spike generation. When the tonic glutamatergic and GABAergic conductances are replaced by in vivo–like highly fluctuating inputs, on the other hand, the effect of depolarizing GABAergic inputs on the input–output relationship critically depends on the degree of coincidence between glutamatergic input events and GABAergic ones. Although a wide range of depolarizing GABAergic inputs hardly changes the firing rate of a neuron driven by noncoincident glutamatergic inputs, a certain range of these inputs considerably decreases the firing rate if a large number of driving glutamatergic inputs are coincident with them. These results raise the possibility that the depolarized GABAA reversal potential is not a paradoxical mystery, but is instead a sophisticated device for discriminative firing rate modulation.

scholarly journals In Vivo Two-photon Imaging Of Experience-dependent Molecular Changes In Cortical Neurons

10.3791/50148 ◽  
2013 ◽  
Author(s):  
Vania Y. Cao ◽  
Yizhou Ye ◽  
Surjeet S. Mastwal ◽  
David M. Lovinger ◽  
Rui M. Costa ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Molecular Changes ◽  
Two Photon ◽  
Photon Imaging ◽  
Two Photon Imaging

In Vivo Calcium Imaging of Neural Network Function

Physiology ◽  
2007 ◽  
Vol 22 (6) ◽  
pp. 358-365 ◽  
Author(s):  
Werner Göbel ◽  
Fritjof Helmchen
Keyword(s):  
Calcium Imaging ◽  
Activity Patterns ◽  
Network Activity ◽  
Network Function ◽  
Two Photon ◽  
Calcium Indicators ◽  
Recent Developments ◽  
In Vivo Calcium Imaging ◽  
Function Network

Spatiotemporal activity patterns in local neural networks are fundamental to brain function. Network activity can now be measured in vivo using two-photon imaging of cell populations that are labeled with fluorescent calcium indicators. In this review, we discuss basic aspects of in vivo calcium imaging and highlight recent developments that will help to uncover operating principles of neural circuits.

scholarly journals Striatal seeding of protofibrillar alpha-synuclein causes cortical hyperreactivity in behaving mice

2020 ◽  
Author(s):  
Sonja Blumenstock ◽  
Fanfan Sun ◽  
Petar Marinković ◽  
Carmelo Sgobio ◽  
Sabine Liebscher ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Alpha Synuclein ◽  
Cellular Level ◽  
Neuronal Function ◽  
Two Photon ◽  
Neuron Function ◽  
The Impact ◽  
Self Aggregation ◽  
Intrastriatal Injection

SummaryAlpha-synucleinopathies are characterized by self-aggregation of the protein alpha-synuclein (a-syn), causing alterations on the molecular and cellular level. To unravel the impact of transneuronal spreading and templated misfolding of a-syn on the microcircuitry of remotely connected brain areas, we investigated cortical neuron function in awake mice 9 months after a single intrastriatal injection of a-syn preformed fibrils (PFFs), using in vivo two-photon calcium imaging. We found altered function of layer 2/3 cortical neurons in somatosensory cortex (S1) of PFF-inoculated mice, as witnessed by an enhanced response to whisking and increased synchrony, accompanied by a decrease in baseline Ca2+ levels. Stereological analyses revealed a reduction in GAD67-positive inhibitory cells in S1 in PFF-injected brains. These findings point to a disturbed excitation/inhibition balance as an important pathomechanism in alpha-synucleinopathies and demonstrate a clear association between the spread of toxic proteins and the initiation of altered neuronal function in remotely connected areas.

Neural architecture of the electrosensory lateral line lobe: adaptations for coincidence detection, a sensory searchlight and frequency-dependent adaptive filtering

1999 ◽  
Vol 202 (10) ◽  
pp. 1243-1253 ◽  
Author(s):  
N.J. Berman ◽  
L. Maler
Keyword(s):  
Lateral Line ◽  
Activity Patterns ◽  
Pyramidal Cells ◽  
Coincidence Detection ◽  
Weakly Electric Fish ◽  
In Vivo Studies ◽  
Frequency Dependent ◽  
Postsynaptic Potentials

The electrosensory lateral line lobe (ELL) of weakly electric fish is the only nucleus that receives direct input from peripheral electroreceptor afferents. This review summarises the neurotransmitters, receptors and second messengers identified in the intrinsic circuitry of the ELL and the extrinsic descending direct and indirect feedback pathways, as revealed by recent in vitro and in vivo studies. Several hypotheses of circuitry function are examined on this basis and on the basis of recent functional evidence: (1) fast primary afferent excitatory postsynaptic potentials (EPSPs) and fast granule cell 2 GABAA inhibitory postsynaptic potentials (IPSPs) suggest the involvement of basilar pyramidal cells in coincidence detection; (2) voltage-dependent EPSPs and IPSPs, dendritic spike bursts and frequency-dependent synaptic facilitation support a sensory searchlight role for the direct feedback pathway; and (3) the contributions of distal and proximal inhibition, anti-Hebbian plasticity and beam versus isolated fiber activity patterns are discussed with reference to an adaptive spatio-temporal filtering role for the indirect descending pathway.

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