Submillisecond Precision of the Input-Output Transformation Function Mediated by Fast Sodium Dendritic Spikes in Basal Dendrites of CA1 Pyramidal Neurons

Thin basal dendrites can strongly influence neuronal output via generation of dendritic spikes. It was recently postulated that glial processes actively support dendritic spikes by either ceasing glutamate uptake or by actively releasing glutamate and adenosine triphosphate (ATP). We used calcium imaging to study the role of NR2C/D-containing N -methyl- d -aspartate (NMDA) receptors and adenosine A1 receptors in the generation of dendritic NMDA spikes and plateau potentials in basal dendrites of layer 5 pyramidal neurons in the mouse prefrontal cortex. We found that NR2C/D glutamate receptor subunits contribute to the amplitude of synaptically evoked NMDA spikes. Dendritic calcium signals associated with glutamate-evoked dendritic plateau potentials were significantly shortened upon application of the NR2C/D receptor antagonist PPDA, suggesting that NR2C/D receptors prolong the duration of calcium influx during dendritic spiking. In contrast to NR2C/D receptors, adenosine A1 receptors act to abbreviate dendritic and somatic signals via the activation of dendritic K + current. This current is characterized as a slow-activating outward-rectifying voltage- and adenosine-gated current, insensitive to 4-aminopyridine but sensitive to TEA. Our data support the hypothesis that the release of glutamate and ATP from neurons or glia contribute to initiation, maintenance and termination of local dendritic glutamate-mediated regenerative potentials.

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Dendritic spikes in apical oblique dendrites of cortical layer 5 pyramidal neurons

10.1101/2020.08.15.252080 ◽

2020 ◽

Cited By ~ 1

Author(s):

Michael Lawrence G. Castañares ◽

Greg J. Stuart ◽

Vincent R. Daria

Keyword(s):

Sensory Processing ◽

Pyramidal Neurons ◽

Low Frequency ◽

Cortical Layer ◽

Voltage Gated ◽

Voltage Gated Calcium Channels ◽

Basal Dendrites ◽

Dendritic Spikes ◽

Specific Computation

AbstractDendritic spikes in layer 5 pyramidal neurons (L5PNs) play a major role in cortical computation. While dendritic spikes have been studied extensively in apical and basal dendrites of L5PNs, whether oblique dendrites, which ramify in the input layers of the cortex, also generate dendritic spikes is unknown. Here we report the existence of dendritic spikes in apical oblique dendrites of L5PNs. In silico investigations indicate that oblique branch spikes are triggered by brief, low-frequency action potential (AP) trains (~40 Hz) and are characterized by a fast sodium spike followed by activation of voltage-gated calcium channels. In vitro experiments confirmed the existence of oblique branch spikes in L5PNs during brief AP trains at frequencies of around 60 Hz. Oblique branch spikes offer new insights into branch-specific computation in L5PNs and may be critical for sensory processing in the input layers of the cortex.

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Lateral entorhinal cortex inputs modulate hippocampal dendritic excitability by recruiting a local disinhibitory microcircuit

10.1101/2022.01.13.476247 ◽

2022 ◽

Author(s):

Olesia M Bilash ◽

Spyridon Chavlis ◽

Panayiota Poirazi ◽

Jayeeta Basu

Keyword(s):

Entorhinal Cortex ◽

Pyramidal Neurons ◽

Inhibitory Neuron ◽

Inhibitory Neurons ◽

Environmental Cues ◽

Memory Processing ◽

Ca1 Pyramidal Neurons ◽

Dendritic Spikes ◽

Hippocampal Area ◽

Insight Into

The lateral entorhinal cortex (LEC) provides information about multi-sensory environmental cues to the hippocampus through direct inputs to the distal dendrites of CA1 pyramidal neurons. A growing body of work suggests that LEC neurons perform important functions for episodic memory processing, coding for contextually-salient elements of an environment or the experience within it. However, we know little about the functional circuit interactions between LEC and the hippocampus. In this study, we combine functional circuit mapping and computational modeling to examine how long-range glutamatergic LEC projections modulate compartment-specific excitation-inhibition dynamics in hippocampal area CA1. We demonstrate that glutamatergic LEC inputs can drive local dendritic spikes in CA1 pyramidal neurons, aided by the recruitment of a disinhibitory vasoactive intestinal peptide (VIP)-expressing inhibitory neuron microcircuit. Our circuit mapping further reveals that, in parallel, LEC also recruits cholecystokinin (CCK)-expressing inhibitory neurons, which our model predicts act as a strong suppressor of dendritic spikes. These results provide new insight into a cortically-driven GABAergic microcircuit mechanism that gates non-linear dendritic computations, which may support compartment-specific coding of multi-sensory contextual features within the hippocampus.

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On the Initiation and Propagation of Dendritic Spikes in CA1 Pyramidal Neurons

Journal of Neuroscience ◽

10.1523/jneurosci.2520-04.2004 ◽

2004 ◽

Vol 24 (49) ◽

pp. 11046-11056 ◽

Cited By ~ 181

Author(s):

S. Gasparini

Keyword(s):

Pyramidal Neurons ◽

Ca1 Pyramidal Neurons ◽

Initiation And Propagation ◽

Dendritic Spikes

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Input-Output Relationship of CA1 Pyramidal Neurons Reveals Intact Homeostatic Mechanisms in a Mouse Model of Fragile X Syndrome

Cell Reports ◽

10.1016/j.celrep.2020.107988 ◽

2020 ◽

Vol 32 (6) ◽

pp. 107988 ◽

Cited By ~ 1

Author(s):

Sam A. Booker ◽

Laura Simões de Oliveira ◽

Natasha J. Anstey ◽

Zrinko Kozic ◽

Owen R. Dando ◽

...

Keyword(s):

Mouse Model ◽

Fragile X Syndrome ◽

Pyramidal Neurons ◽

Fragile X ◽

Input Output ◽

Ca1 Pyramidal Neurons ◽

Relationship Of ◽

Homeostatic Mechanisms

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Dendrite-to-Soma Input/Output Function of Continuous Time-Varying Signals in Hippocampal CA1 Pyramidal Neurons

Journal of Neurophysiology ◽

10.1152/jn.00414.2007 ◽

2007 ◽

Vol 98 (5) ◽

pp. 2943-2955 ◽

Cited By ~ 25

Author(s):

Erik P. Cook ◽

Jennifer A. Guest ◽

Yong Liang ◽

Nicolas Y. Masse ◽

Costa M. Colbert

Keyword(s):

Pyramidal Neurons ◽

Gain Control ◽

Linear Filter ◽

Band Pass Filter ◽

Time Varying ◽

Input Output ◽

Frequency Range ◽

Pass Filter ◽

Ca1 Pyramidal Neurons ◽

Band Pass

We examined how hippocamal CA1 neurons process complex time-varying inputs that dendrites are likely to receive in vivo. We propose a functional model of the dendrite-to-soma input/output relationship that combines temporal integration and static-gain control mechanisms. Using simultaneous dual whole cell recordings, we injected 50 s of subthreshold and suprathreshold zero-mean white-noise current into the primary dendritic trunk along the proximal 2/3 of stratum radiatum and measured the membrane potential at the soma. Applying a nonlinear system-identification analysis, we found that a cascade of a linear filter followed by an adapting static-gain term fully accounted for the nonspiking input/output relationship between the dendrite and soma. The estimated filters contained a prominent band-pass region in the 1- to 10-Hz frequency range that remained constant as a function of stimulus variance. The gain of the dendrite-to-soma input/output relationship, in contrast, varied as a function of stimulus variance. When the contribution of the voltage-dependent current Ih was eliminated, the estimated filters lost their band-pass properties and the gain regulation was substantially altered. Our findings suggest that the dendrite-to-soma input/output relationship for proximal apical inputs to CA1 pyramidal neurons is well described as a band-pass filter in the theta frequency range followed by a gain-control nonlinearity that dynamically adapts to the statistics of the input signal.

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Background Activity Regulates Excitability of Rat Hippocampal CA1 Pyramidal Neurons by Adaptation of a K+ Conductance

Journal of Neurophysiology ◽

10.1152/jn.00220.2005 ◽

2006 ◽

Vol 95 (3) ◽

pp. 2007-2012 ◽

Cited By ~ 11

Author(s):

Ingrid van Welie ◽

Johannes A. van Hooft ◽

Wytse J. Wadman

Keyword(s):

Neuronal Excitability ◽

Pyramidal Neurons ◽

Dynamic Range ◽

Background Activity ◽

Hippocampal Slices ◽

Synaptic Activity ◽

Input Output ◽

Ca1 Pyramidal Neurons

In the in vivo brain background synaptic activity has a strong modulatory influence on neuronal excitability. Here we report that in rat hippocampal slices, blockade of endogenous in vitro background activity results in an increased excitability of CA1 pyramidal neurons within tens of minutes. The increase in excitability constitutes a leftward shift in the input–output relationship of pyramidal neurons, indicating a reduced threshold for the induction of action potentials. The increase in excitability results from an adaptive decrease in a sustained K+ conductance, as recorded from somatic cell–attached patches. After 20 min of blockade of background activity, the mean sustained K+ current amplitude in somatic patches was reduced to 46 ± 9% of that in time-matched control patches. Blockade of background activity did not affect fast Na+ conductance. Together, these results suggests that the reduction in K+ conductance serves as an adaptive mechanism to increase the excitability of CA1 pyramidal neurons in response to changes in background activity such that the dynamic range of the input–output relationship is effectively maintained.

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Selective Shunting of the NMDA EPSP Component by the Slow Afterhyperpolarization in Rat CA1 Pyramidal Neurons

Journal of Neurophysiology ◽

10.1152/jn.00422.2006 ◽

2007 ◽

Vol 97 (5) ◽

pp. 3242-3255 ◽

Cited By ~ 12

Author(s):

David Fernández de Sevilla ◽

Marco Fuenzalida ◽

Ana B. Porto Pazos ◽

Washington Buño

Keyword(s):

Pyramidal Neurons ◽

Spatial Summation ◽

Decisive Role ◽

Perforant Path ◽

Ca1 Pyramidal Neurons ◽

Basal Dendrites ◽

Hippocampal Ca1 ◽

Dendritic Location ◽

Conductance Increase

Pyramidal neuron dendrites express voltage-gated conductances that control synaptic integration and plasticity, but the contribution of the Ca2+-activated K+-mediated currents to dendritic function is not well understood. Using dendritic and somatic recordings in rat hippocampal CA1 pyramidal neurons in vitro, we analyzed the changes induced by the slow Ca2+-activated K+-mediated afterhyperpolarization (sAHP) generated by bursts of action potentials on excitatory postsynaptic potentials (EPSPs) evoked at the apical dendrites by perforant path-Schaffer collateral stimulation. Both the amplitude and decay time constants of EPSPs (τEPSP) were reduced by the sAHP in somatic recordings. In contrast, the dendritic EPSP amplitude remained unchanged, whereas τEPSP was reduced. Temporal summation was reduced and spatial summation linearized by the sAHP. The amplitude of the isolated N-methyl-d-aspartate component of EPSPs (EPSPNMDA) was reduced, whereas τNMDA was unaffected by the sAHP. In contrast, the sAHP did not modify the amplitude of the isolated EPSPAMPA but reduced τAMPA both in dendritic and somatic recordings. These changes are attributable to a conductance increase that acted mainly via a selective “shunt” of EPSPNMDA because they were absent under voltage clamp, not present with imposed hyperpolarization simulating the sAHP, missing when the sAHP was inhibited with isoproterenol, and reduced under block of EPSPNMDA. EPSPs generated at the basal dendrites were similarly modified by the sAHP, suggesting both a somatic and apical dendritic location of the sAHP channels. Therefore the sAHP may play a decisive role in the dendrites by regulating synaptic efficacy and temporal and spatial summation.

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Distribution of Slow AHP Channels on Hippocampal CA1 Pyramidal Neurons

Journal of Neurophysiology ◽

10.1152/jn.2000.83.3.1756 ◽

2000 ◽

Vol 83 (3) ◽

pp. 1756-1759 ◽

Cited By ~ 34

Author(s):

John M. Bekkers

Keyword(s):

Action Potentials ◽

Pyramidal Neurons ◽

Pyramidal Cells ◽

Apical Dendrite ◽

Ca1 Pyramidal Cells ◽

Ca1 Pyramidal Neurons ◽

Basal Dendrites ◽

Hippocampal Ca1 ◽

Cell Current ◽

Whole Cell Current

This work was designed to localize the Ca2+-activated K+ channels underlying the slow afterhyperpolarization (sAHP) in hippocampal CA1 pyramidal cells. Cell-attached patches on the proximal 100 μm of the apical dendrite contained K+ channels, but not sAHP channels, activated by backpropagating action potentials. Amputation of the apical dendrite ∼30 μm from the soma, while simultaneously recording the sAHP whole cell current at the soma, depressed the sAHP amplitude by only ∼30% compared with control. Somatic cell-attached and nucleated patches did not contain sAHP current. Amputation of the axon ≥20 μm from the soma had little effect on the amplitude of the sAHP recorded in cortical pyramidal cells. By this process of elimination, it is suggested that sAHP channels may be concentrated in the basal dendrites of CA1 pyramids.

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