scholarly journals Neuronal gain modulability is determined by dendritic morphology: a computational optogenetic study

2016 ◽  
Author(s):  
Sarah Jarvis ◽  
Konstantin Nikolic ◽  
Simon R Schultz
Keyword(s):  
Dendritic Tree ◽  
Gain Control ◽  
Pyramidal Cells ◽  
Dendritic Morphology ◽  
Inhibitory Input ◽  
List Type ◽  
Moderate Degree ◽  
Gain Modulation ◽  
Input Output

AbstractThe mechanisms by which the gain of the neuronal input-output function may be modulated have been the subject of much investigation. However, little is known of the role of dendrites in neuronal gain control. New optogenetic experimental paradigms based on spatial profiles or patterns of light stimulation offer the prospect of elucidating many aspects of single cell function, including the role of dendrites in gain control. We thus developed a model to investigate how competing excitatory and inhibitory input within the dendritic arbor alters neuronal gain, incorporating kinetic models of opsins into our modeling to ensure it is experimentally testable. To investigate how different topologies of the neuronal dendritic tree affect the neuron’s input-output characteristics we generate branching geometries which replicate morphological features of most common neurons, but keep the number of branches and overall area of dendrites approximately constant. We found a relationship between a neuron’s gain modulability and its dendritic morphology, with neurons with bipolar dendrites with a moderate degree of branching being most receptive to control of the gain of their input-output relationship. The theory was then tested and confirmed on two examples of realistic neurons: 1) layer V pyramidal cells - confirming their role in neural circuits as a regulator of the gain in the circuit in addition to acting as the primary excitatory neurons, and 2) stellate cells. In addition to providing testable predictions and a novel application of dual-opsins, our model suggests that innervation of all dendritic subdomains is required for full gain modulation, revealing the importance of dendritic targeting in the generation of neuronal gain control and the functions that it subserves. Finally, our study also demonstrates that neurophysiological investigations which use direct current injection into the soma and bypass the dendrites may miss some important neuronal functions, such as gain modulation.Author SummaryGain modulability indicated by dendritic morphologyPyramidal cell-like shapes optimally receptive to modulationAll dendritic subdomains required for gain modulation, partial illumination is insufficientComputational optogenetic models improve and refine experimental protocols

scholarly journals Functional and structural features of L2/3 pyramidal cells continuously covary with pial depth in mouse visual cortex

2021 ◽  
Author(s):  
Simon Weiler ◽  
Drago Guggiana Nilo ◽  
Tobias Bonhoeffer ◽  
Mark H&uumlbener ◽  
Tobias Rose ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Dendritic Tree ◽  
Pyramidal Cells ◽  
Structural Features ◽  
Direction Selectivity ◽  
Dendritic Morphology ◽  
Systematic Change ◽  
Inhibitory Input ◽  
Electrophysiological Properties

Pyramidal cells of neocortical layer 2/3 (L2/3 PyrCs) integrate signals from numerous brain areas and project throughout the neocortex. Within L2/3, PyrCs show functional and structural specializations depending on their pial depth, indicating participation in different functional microcircuits. However, it is unknown whether these depth-dependent differences result from separable L2/3 PyrC subtypes or whether functional and structural features represent a continuum while correlating with pial depth. Here, we assessed the stimulus selectivity, electrophysiological properties, dendritic morphology, and excitatory and inhibitory synaptic connectivity across the depth of L2/3 in the binocular visual cortex (bV1) of female mice. We find that the structure of the apical but not the basal dendritic tree varies with pial depth, which is accompanied by differences in passive but not active electrophysiological properties. PyrCs in lower L2/3 receive increased excitatory and inhibitory input from L4, while upper L2/3 PyrCs receive a larger proportion of intralaminar input. Complementary in vivo calcium imaging revealed a systematic change in visual responsiveness, with deeper L2/3 PyrCs showing more robust responses than superficial PyrCs. Furthermore, deeper L2/3 PyrCs are more strongly driven by contralateral than ipsilateral eye stimulation. In contrast, orientation- and direction-selectivity of L2/3 PyrCs are not dependent on pial depth. Importantly, the transitions of the various properties are gradual, and cluster analysis does not support the classification of L2/3 PyrCs into discrete subtypes. These results show that L2/3 PyrCs' multiple functional and structural properties systematically correlate with their depth within L2/3, forming a continuum rather than representing discrete subtypes.

scholarly journals Distinct dendritic Ca2+ spike forms produce opposing input-output transformations in rat CA3 pyramidal cells

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ádám Magó ◽  
Noémi Kis ◽  
Balázs Lükő ◽  
Judit K Makara
Keyword(s):  
Dendritic Structure ◽  
Dendritic Tree ◽  
Pyramidal Cells ◽  
Afferent Input ◽  
Male Rats ◽  
Input Output ◽  
Single Action ◽  
Two Photon ◽  
Ca3 Pyramidal Cells ◽  
Output Transformation

Proper integration of different inputs targeting the dendritic tree of CA3 pyramidal cells (CA3PCs) is critical for associative learning and recall. Dendritic Ca2+ spikes have been proposed to perform associative computations in other PC types by detecting conjunctive activation of different afferent input pathways, initiating afterdepolarization (ADP), and triggering burst firing. Implementation of such operations fundamentally depends on the actual biophysical properties of dendritic Ca2+ spikes; yet little is known about these properties in dendrites of CA3PCs. Using dendritic patch-clamp recordings and two-photon Ca2+ imaging in acute slices from male rats, we report that, unlike CA1PCs, distal apical trunk dendrites of CA3PCs exhibit distinct forms of dendritic Ca2+ spikes. Besides ADP-type global Ca2+ spikes, a majority of dendrites expresses a novel, fast Ca2+ spike type that is initiated locally without bAPs, can recruit additional Na+ currents, and is compartmentalized to the activated dendritic subtree. Occurrence of the different Ca2+ spike types correlates with dendritic structure, indicating morpho-functional heterogeneity among CA3PCs. Importantly, ADPs and dendritically initiated spikes produce opposing somatic output: bursts versus strictly single-action potentials, respectively. The uncovered variability of dendritic Ca2+ spikes may underlie heterogeneous input-output transformation and bursting properties of CA3PCs, and might specifically contribute to key associative and non-associative computations performed by the CA3 network.

Propagation of Action Potentials in Dendrites Depends on Dendritic Morphology

2001 ◽  
Vol 85 (2) ◽  
pp. 926-937 ◽  
Author(s):  
Philipp Vetter ◽  
Arnd Roth ◽  
Michael Häusser
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Dendritic Tree ◽  
Pyramidal Cells ◽  
Dendritic Morphology ◽  
Dopamine Neurons ◽  
Action Potential Propagation ◽  
Voltage Gated ◽  
Wide Range ◽  
Gated Channel

Action potential propagation links information processing in different regions of the dendritic tree. To examine the contribution of dendritic morphology to the efficacy of propagation, simulations were performed in detailed reconstructions of eight different neuronal types. With identical complements of voltage-gated channels, different dendritic morphologies exhibit distinct patterns of propagation. Remarkably, the range of backpropagation efficacies observed experimentally can be reproduced by the variations in dendritic morphology alone. Dendritic geometry also determines the extent to which modulation of channel densities can affect propagation. Thus in Purkinje cells and dopamine neurons, backpropagation is relatively insensitive to changes in channel densities, whereas in pyramidal cells, backpropagation can be modulated over a wide range. We also demonstrate that forward propagation of dendritically initiated action potentials is influenced by morphology in a similar manner. We show that these functional consequences of the differences in dendritic geometries can be explained quantitatively using simple anatomical measures of dendritic branching patterns, which are captured in a reduced model of dendritic geometry. These findings indicate that differences in dendritic geometry act in concert with differences in voltage-gated channel density and kinetics to generate the diversity in dendritic action potential propagation observed between neurons. They also suggest that changes in dendritic geometry during development and plasticity will critically affect propagation. By determining the spatial pattern of action potential signaling, dendritic morphology thus helps to define the size and interdependence of functional compartments in the neuron.

scholarly journals A general principle of dendritic constancy – a neuron’s size and shape invariant excitability

2019 ◽  
Author(s):  
Hermann Cuntz ◽  
Alexander D Bird ◽  
Marcel Beining ◽  
Marius Schneider ◽  
Laura Mediavilla ◽  
...  
Keyword(s):  
Dendritic Morphology ◽  
Spike Timing ◽  
List Type ◽  
Input Output ◽  
Neuron Models ◽  
Dendrite Morphology ◽  
Synaptic Inputs ◽  
Size And Shape ◽  
Dendritic Length ◽  
The Impact

AbstractReducing neuronal size results in less cell membrane and therefore lower input conductance. Smaller neurons are thus more excitable as seen in their voltage responses to current injections in the soma. However, the impact of a neuron’s size and shape on its voltage responses to synaptic activation in dendrites is much less understood. Here we use analytical cable theory to predict voltage responses to distributed synaptic inputs and show that these are entirely independent of dendritic length. For a given synaptic density, a neuron’s response depends only on the average dendritic diameter and its intrinsic conductivity. These results remain true for the entire range of possible dendritic morphologies irrespective of any particular arborisation complexity. Also, spiking models result in morphology invariant numbers of action potentials that encode the percentage of active synapses. Interestingly, in contrast to spike rate, spike times do depend on dendrite morphology. In summary, a neuron’s excitability in response to synaptic inputs is not affected by total dendrite length. It rather provides a homeostatic input-output relation that specialised synapse distributions, local non-linearities in the dendrites and synaptic plasticity can modulate. Our work reveals a new fundamental principle of dendritic constancy that has consequences for the overall computation in neural circuits.In briefWe show that realistic neuron models essentially collapse to point neurons when stimulated by randomly distributed inputs instead of by single synapses or current injection in the soma.HighlightsA simple equation that predicts voltage in response to distributed synaptic inputs.Responses to distributed and clustered inputs are largely independent of dendritic length.Spike rates in various Hodgkin Huxley (HH) like or Leaky Integrate-and-Fire (LIF) models are largely independent of morphology.Precise spike timing (firing pattern) depends on dendritic morphology.NeuroMorpho.Org database-wide analysis of the relation between dendritic morphology and electrophysiology.Our equations set precise input-output relations in realistic dendrite models.

SHAPING NEURONAL DENDRITES: INTERPLAY OF TOPOLOGICAL AND METRICAL PARAMETERS

1995 ◽  
Vol 03 (04) ◽  
pp. 1193-1200 ◽  
Author(s):  
ANDREAS K. SCHIERWAGEN ◽  
JAAP VAN PELT
Keyword(s):  
Radial Distance ◽  
Dendritic Tree ◽  
Pyramidal Cells ◽  
Topological Parameters ◽  
Neuronal Dendrites ◽  
Simulation Results ◽  
Superior Colliculus Neurons ◽  
The Relationship ◽  
Cat Superior Colliculus

The functional role of a neuron within a network is influenced by the geometry of its dendrites. In the present study we have used a new model of dendritic arborization to analyze how metrical and topological parameters interact to shape a certain dendritic tree. One of the specific questions addressed is how to change topological variability in a systematic way while preserving the metrical features. The second problem concerns the effect of topology on the relationship between dendritic size and the distribution of dendritic surface area with radial distance from soma. The simulation results reproduce features of dendritic architecture found in neocortical pyramidal cells and cat superior colliculus neurons.

scholarly journals Distinct dendritic Ca2+ spike forms produce opposing input-output transformations in rat CA3 pyramidal cells

2021 ◽  
Author(s):  
Ádám Magó ◽  
Noémi Kis ◽  
Balázs Lükó ◽  
Judit K Makara
Keyword(s):  
Action Potentials ◽  
Dendritic Structure ◽  
Dendritic Tree ◽  
Pyramidal Cells ◽  
Afferent Input ◽  
Male Rats ◽  
Input Output ◽  
Single Action ◽  
Na Currents ◽  
Ca3 Pyramidal Cells

Proper integration of different inputs targeting the dendritic tree of CA3 pyramidal cells (CA3PCs) is critical for associative learning and recall. Dendritic Ca2+ spikes have been proposed to perform associative computations in other PC types, by detecting conjunctive activation of different afferent input pathways, initiating afterdepolarization (ADP) and triggering burst firing. Implementation of such operations fundamentally depends on the actual biophysical properties of dendritic Ca2+ spikes; yet little is known about these properties in dendrites of CA3PCs. Using dendritic patch-clamp recordings and two-photon Ca2+ imaging in acute slices from male rats we report that, unlike CA1PCs, distal apical trunk dendrites of CA3PCs exhibit distinct forms of dendritic Ca2+ spikes. Besides ADP-type global Ca2+ spikes, a majority of dendrites expresses a novel, fast Ca2+ spike type that is initiated locally without backpropagating action potentials, can recruit additional Na+ currents, and is compartmentalized to the activated dendritic subtree. Occurrence of the different Ca2+ spike types correlates with dendritic structure, indicating morpho-functional heterogeneity among CA3PCs. Importantly, ADPs and dendritically initiated spikes produce opposing somatic output: bursts versus strictly single action potentials, respectively. The uncovered variability of dendritic Ca2+ spikes may underlie heterogeneous input-output transformation and bursting properties of CA3PCs, and might specifically contribute to key associative and non-associative computations performed by the CA3 network.

scholarly journals Early oxygen levels contribute to brain injury in extremely preterm infants

2021 ◽  
Author(s):  
Krista Rantakari ◽  
Olli-Pekka Rinta-Koski ◽  
Marjo Metsäranta ◽  
Jaakko Hollmén ◽  
Simo Särkkä ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Brain Structures ◽  
High Oxygen ◽  
List Type ◽  
Neurodevelopmental Outcomes ◽  
Oxygen Levels ◽  
Arterial Blood ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Abstract Background Extremely low gestational age newborns (ELGANs) are at risk of neurodevelopmental impairments that may originate in early NICU care. We hypothesized that early oxygen saturations (SpO2), arterial pO2 levels, and supplemental oxygen (FiO2) would associate with later neuroanatomic changes. Methods SpO2, arterial blood gases, and FiO2 from 73 ELGANs (GA 26.4 ± 1.2; BW 867 ± 179 g) during the first 3 postnatal days were correlated with later white matter injury (WM, MRI, n = 69), secondary cortical somatosensory processing in magnetoencephalography (MEG-SII, n = 39), Hempel neurological examination (n = 66), and developmental quotients of Griffiths Mental Developmental Scales (GMDS, n = 58). Results The ELGANs with later WM abnormalities exhibited lower SpO2 and pO2 levels, and higher FiO2 need during the first 3 days than those with normal WM. They also had higher pCO2 values. The infants with abnormal MEG-SII showed opposite findings, i.e., displayed higher SpO2 and pO2 levels and lower FiO2 need, than those with better outcomes. Severe WM changes and abnormal MEG-SII were correlated with adverse neurodevelopment. Conclusions Low oxygen levels and high FiO2 need during the NICU care associate with WM abnormalities, whereas higher oxygen levels correlate with abnormal MEG-SII. The results may indicate certain brain structures being more vulnerable to hypoxia and others to hyperoxia, thus emphasizing the role of strict saturation targets. Impact This study indicates that both abnormally low and high oxygen levels during early NICU care are harmful for later neurodevelopmental outcomes in preterm neonates. Specific brain structures seem to be vulnerable to low and others to high oxygen levels. The findings may have clinical implications as oxygen is one of the most common therapies given in NICUs. The results emphasize the role of strict saturation targets during the early postnatal period in preterm infants.

scholarly journals 332 The diagnostic role of shunt series radiographs (SSR) in children presenting to the children’s emergency department (CED) with suspected ventriculoperitoneal (VP) shunt failure

2020 ◽  
Vol 37 (12) ◽  
pp. 852.3-853
Author(s):  
Angharad Griffiths ◽  
Ikechukwu Okafor ◽  
Thomas Beattie
Keyword(s):  
Clinical Outcome ◽  
Sensitivity And Specificity ◽  
Clinical Information ◽  
Flow Diagram ◽  
List Type ◽  
Shunt Failure ◽  
Vp Shunt ◽  
Wide Range ◽  
Diagnostic Role

Aims/Objectives/BackgroundVP shunts are used to drain CSF from the cranial vault because of a wide range of pathologies and, like any piece of hardware, can fail. Traditionally investigations include SSR and CT. This project examines the role of SSR in evaluating children with suspected VP shunt failure.Primary outcome: Sensitivity and specificity of SSR in children presenting to the CED with concern for shunt failure.Methods/DesignConducted in a single centre, tertiary CED of the national Irish Neurosurgical(NS) referral centre (ED attendance:>50,000 patients/year). 100 sequential SSR requested by the CED were reviewed. Clinical information was extracted from electronic requests. Shunt failure was defined by the need for NS intervention(Revision).Abstract 332 Figure 1Abstract 332 Figure 2Results/ConclusionsSensitivity and specificity is presented in figure 1 (two by two table).100 radiographs performed in 84 children.22% shunts revised (see flow diagram).7 SSR’s were abnormal.85% (n=6) shunts revised. [5 following abnormal CT].Of the normal SSR’s; 16 had abnormal CT and revised.85/100 received CT.64 of 85 CT’s (75%) were normal.□6 of the 64 had focal shunt concern.SSR’s shouldn’t be used in isolation. NPV&PPV, Sensitivity&Specificity is low.SSR’s are beneficial where there’s concern over focal shunt problems (injury/pain/swelling) or following abnormal CT.VP shunt failure is not well investigated with SSR alone.SSR’s could be omitted where there is no focal shunt concern/after normal CT (without impacting clinical outcome) reducing radiation exposure and reduce impact on CED’s.59 SSR’s could have been avoided without adverse clinical outcome.

scholarly journals Hippocampal Interneurons are Required for Trace Eyeblink Conditioning in Mice

2021 ◽  
Author(s):  
Wei-Wei Zhang ◽  
Rong-Rong Li ◽  
Jie Zhang ◽  
Jie Yan ◽  
Qian-Hui Zhang ◽  
...  
Keyword(s):  
Eyeblink Conditioning ◽  
Pyramidal Cells ◽  
Conditioned Eyeblink ◽  
Cellular Mechanisms ◽  
Sustained Activity ◽  
Early Acquisition ◽  
Freely Moving ◽  
Trace Eyeblink Conditioning

AbstractWhile the hippocampus has been implicated in supporting the association among time-separated events, the underlying cellular mechanisms have not been fully clarified. Here, we combined in vivo multi-channel recording and optogenetics to investigate the activity of hippocampal interneurons in freely-moving mice performing a trace eyeblink conditioning (tEBC) task. We found that the hippocampal interneurons exhibited conditioned stimulus (CS)-evoked sustained activity, which predicted the performance of conditioned eyeblink responses (CRs) in the early acquisition of the tEBC. Consistent with this, greater proportions of hippocampal pyramidal cells showed CS-evoked decreased activity in the early acquisition of the tEBC. Moreover, optogenetic suppression of the sustained activity in hippocampal interneurons severely impaired acquisition of the tEBC. In contrast, suppression of the sustained activity of hippocampal interneurons had no effect on the performance of well-learned CRs. Our findings highlight the role of hippocampal interneurons in the tEBC, and point to a potential cellular mechanism subserving associative learning.

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