scholarly journals Dendritic Na+ spikes enable cortical input to drive action potential output from hippocampal CA2 pyramidal neurons

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Qian Sun ◽  
Kalyan V Srinivas ◽  
Alaba Sotayo ◽  
Steven A Siegelbaum
Keyword(s):  
Action Potential ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Brain Areas ◽  
Cortical Input ◽  
Strong Excitation ◽  
Dendritic Spikes ◽  
Efficient Coupling ◽  
Dendritic Arbors ◽  
Cortical Inputs

Synaptic inputs from different brain areas are often targeted to distinct regions of neuronal dendritic arbors. Inputs to proximal dendrites usually produce large somatic EPSPs that efficiently trigger action potential (AP) output, whereas inputs to distal dendrites are greatly attenuated and may largely modulate AP output. In contrast to most other cortical and hippocampal neurons, hippocampal CA2 pyramidal neurons show unusually strong excitation by their distal dendritic inputs from entorhinal cortex (EC). In this study, we demonstrate that the ability of these EC inputs to drive CA2 AP output requires the firing of local dendritic Na+ spikes. Furthermore, we find that CA2 dendritic geometry contributes to the efficient coupling of dendritic Na+ spikes to AP output. These results provide a striking example of how dendritic spikes enable direct cortical inputs to overcome unfavorable distal synaptic locale to trigger axonal AP output and thereby enable efficient cortico-hippocampal information flow.

scholarly journals Distinct roles for motor cortical and thalamic inputs to striatum during motor learning and execution

2019 ◽  
Author(s):  
Steffen B. E. Wolff ◽  
Raymond Ko ◽  
Bence P. Ölveczky
Keyword(s):  
Motor Cortex ◽  
Motor Learning ◽  
Learning Process ◽  
Brain Areas ◽  
Thalamic Neurons ◽  
Cortical Input ◽  
Motor Circuits ◽  
Motor Network ◽  
Motor Cortical ◽  
Cortical Inputs

AbstractThe acquisition and execution of learned motor sequences are mediated by a distributed motor network, spanning cortical and subcortical brain areas. The sensorimotor striatum is an important cog in this network, yet how its two main inputs, from motor cortex and thalamus respectively, contribute to its role in motor learning and execution remains largely unknown. To address this, we trained rats in a task that produces highly stereotyped and idiosyncratic motor sequences. We found that motor cortical input to the sensorimotor striatum is critical for the learning process, but after the behaviors were consolidated, this corticostriatal pathway became dispensable. Functional silencing of striatal-projecting thalamic neurons, however, disrupted the execution of the learned motor sequences, causing rats to revert to behaviors produced early in learning and preventing them from re-learning the task. These results show that the sensorimotor striatum is a conduit through which motor cortical inputs can drive experience-dependent changes in subcortical motor circuits, likely at thalamostriatal synapses.

scholarly journals Active dendrites enable strong but sparse inputs to determine orientation selectivity

2021 ◽  
Vol 118 (30) ◽  
pp. e2017339118
Author(s):  
Lea Goetz ◽  
Arnd Roth ◽  
Michael Häusser
Keyword(s):  
Action Potential ◽  
Pyramidal Neurons ◽  
Potential Output ◽  
Synaptic Inputs ◽  
Active Dendrites ◽  
Strongly Connected ◽  
Dendritic Spikes ◽  
Sensory Responses

The dendrites of neocortical pyramidal neurons are excitable. However, it is unknown how synaptic inputs engage nonlinear dendritic mechanisms during sensory processing in vivo, and how they in turn influence action potential output. Here, we provide a quantitative account of the relationship between synaptic inputs, nonlinear dendritic events, and action potential output. We developed a detailed pyramidal neuron model constrained by in vivo dendritic recordings. We drive this model with realistic input patterns constrained by sensory responses measured in vivo and connectivity measured in vitro. We show mechanistically that under realistic conditions, dendritic Na+ and NMDA spikes are the major determinants of neuronal output in vivo. We demonstrate that these dendritic spikes can be triggered by a surprisingly small number of strong synaptic inputs, in some cases even by single synapses. We predict that dendritic excitability allows the 1% strongest synaptic inputs of a neuron to control the tuning of its output. Active dendrites therefore allow smaller subcircuits consisting of only a few strongly connected neurons to achieve selectivity for specific sensory features.

scholarly journals Theta Modulation in the Medial and the Lateral Entorhinal Cortices

2010 ◽  
Vol 104 (2) ◽  
pp. 994-1006 ◽  
Author(s):  
Sachin S. Deshmukh ◽  
D. Yoganarasimha ◽  
Horatiu Voicu ◽  
James J. Knierim
Keyword(s):  
Entorhinal Cortex ◽  
Hippocampal Neurons ◽  
Theta Oscillations ◽  
Neural Firing ◽  
Physiological Mechanisms ◽  
Cortical Input ◽  
Theta Frequency ◽  
Temporal Encoding ◽  
Cortical Inputs ◽  
Delta Oscillations

Hippocampal neurons show a strong modulation by theta frequency oscillations. This modulation is thought to be important not only for temporal encoding and decoding of information in the hippocampal system, but also for temporal ordering of neuronal activities on timescales at which physiological mechanisms of synaptic plasticity operate. The medial entorhinal cortex (MEC), one of the two major cortical inputs to the hippocampus, is known to show theta modulation. Here, we show that the local field potentials (LFPs) in the other major cortical input to the hippocampus, the lateral entorhinal cortex (LEC), show weaker theta oscillations than those shown in the MEC. Neurons in LEC also show weaker theta modulation than that of neurons in MEC. These findings suggest that LEC inputs are integrated into hippocampal representations in a qualitatively different manner than the MEC inputs. Furthermore, MEC grid cells increase the scale of their periodic spatial firing patterns along the dorsoventral axis, corresponding to the increasing size of place fields along the septotemporal axis of the hippocampus. We show here a corresponding gradient in the tendency of MEC neural firing to skip alternate theta cycles. We propose a simple model based on interference of delta oscillations with theta oscillations to explain this behavior.

scholarly journals Small-conductance Ca2+-activated K+ channels modulate action potential-induced Ca2+ transients in hippocampal neurons

2013 ◽  
Vol 109 (6) ◽  
pp. 1514-1524 ◽  
Author(s):  
Raffaella Tonini ◽  
Teresa Ferraro ◽  
Marisol Sampedro-Castañeda ◽  
Anna Cavaccini ◽  
Martin Stocker ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Apical Dendrite ◽  
Channel Blockers ◽  
Sk Channels ◽  
Hippocampal Pyramidal Neurons ◽  
Voltage Gated ◽  
Small Conductance

In hippocampal pyramidal neurons, voltage-gated Ca2+ channels open in response to action potentials. This results in elevations in the intracellular concentration of Ca2+ that are maximal in the proximal apical dendrites and decrease rapidly with distance from the soma. The control of these action potential-evoked Ca2+ elevations is critical for the regulation of hippocampal neuronal activity. As part of Ca2+ signaling microdomains, small-conductance Ca2+-activated K+ (SK) channels have been shown to modulate the amplitude and duration of intracellular Ca2+ signals by feedback regulation of synaptically activated Ca2+ sources in small distal dendrites and dendritic spines, thus affecting synaptic plasticity in the hippocampus. In this study, we investigated the effect of the activation of SK channels on Ca2+ transients specifically induced by action potentials in the proximal processes of hippocampal pyramidal neurons. Our results, obtained by using selective SK channel blockers and enhancers, show that SK channels act in a feedback loop, in which their activation by Ca2+ entering mainly through L-type voltage-gated Ca2+ channels leads to a reduction in the subsequent dendritic influx of Ca2+. This underscores a new role of SK channels in the proximal apical dendrite of hippocampal pyramidal neurons.

scholarly journals Factors Underlying Bursting Behavior in a Network of Cultured Hippocampal Neurons Exposed to Zero Magnesium

2004 ◽  
Vol 91 (2) ◽  
pp. 946-957 ◽  
Author(s):  
Patrick S. Mangan ◽  
Jaideep Kapur
Keyword(s):  
Nmda Receptor ◽  
Action Potential ◽  
Receptor Antagonist ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Membrane Surface ◽  
Nmda Receptor Antagonist ◽  
Low Density ◽  
Hippocampal Cell Culture ◽  
Low Culture

Factors contributing to reduced magnesium-induced neuronal action potential bursting were investigated in primary hippocampal cell culture at high and low culture density. In nominally zero external magnesium medium, pyramidal neurons from high-density cultures produced recurrent spontaneous action potential bursts superimposed on prolonged depolarizations. These bursts were partially attenuated by the NMDA receptor antagonist d-APV. Pharmacological analysis of miniature excitatory postsynaptic currents (EPSCs) revealed 2 components: one sensitive to d-APV and another to the AMPA receptor antagonist DNQX. The components were kinetically distinct. Participation of NMDA receptors in reduced magnesium-induced synaptic events was supported by the localization of the NR1 subunit of the NMDA receptor with the presynaptic vesicular protein synaptophysin. Presynaptically, zero magnesium induced a significant increase in EPSC frequency likely attributable to increased neuronal hyperexcitability induced by reduced membrane surface charge screening. Mean quantal content was significantly increased in zero magnesium. Cells from low-density cultures did not exhibit action potential bursting in zero magnesium but did show increased EPSC frequency. Low-density neurons had less synaptophysin immunofluorescence and fewer active synapses as determined by FM1-43 analysis. These results demonstrate that multiple factors are involved in network bursting. Increased probability of transmitter release presynaptically, enhanced NMDA receptor-mediated excitability postsynaptically, and extent of neuronal interconnectivity contribute to initiation and maintenance of elevated network excitability.

scholarly journals Postnatal Development of Dendritic Synaptic Integration in Rat Neocortical Pyramidal Neurons

2009 ◽  
Vol 102 (2) ◽  
pp. 735-751 ◽  
Author(s):  
Susan E. Atkinson ◽  
Stephen R. Williams
Keyword(s):  
Action Potential ◽  
Postnatal Development ◽  
Synaptic Input ◽  
Pyramidal Neurons ◽  
Dendritic Tree ◽  
Action Potential Generation ◽  
Hcn Channel ◽  
Potential Generation ◽  
Site Of Action ◽  
Dendritic Spikes

The dendritic tree of layer 5 (L5) pyramidal neurons spans the neocortical layers, allowing the integration of intra- and extracortical synaptic inputs. Here we investigate the postnatal development of the integrative properties of rat L5 pyramidal neurons using simultaneous whole cell recording from the soma and distal apical dendrite. In young (P9-10) neurons, apical dendritic excitatory synaptic input powerfully drove action potential output by efficiently summating at the axonal site of action potential generation. In contrast, in mature (P25-29) neurons, apical dendritic excitatory input provided little direct depolarization at the site of action potential generation but was integrated locally in the apical dendritic tree leading to the generation of dendritic spikes. Consequently, over the first postnatal month the fraction of action potentials driven by apical dendritic spikes increased dramatically. This developmental remodeling of the integrative operations of L5 pyramidal neurons was controlled by a >10-fold increase in the density of apical dendritic Hyperpolarization-activated cyclic nucleotide (HCN)-gated channels found in cell-attached patches or by immunostaining for the HCN channel isoform HCN1. Thus an age-dependent increase in apical dendritic HCN channel density ensures that L5 pyramidal neurons develop from compact temporal integrators to compartmentalized integrators of basal and apical dendritic synaptic input.

scholarly journals Activity-dependent mismatch between axo-axonic synapses and the axon initial segment controls neuronal output

2015 ◽  
Vol 112 (31) ◽  
pp. 9757-9762 ◽  
Author(s):  
Winnie Wefelmeyer ◽  
Daniel Cattaert ◽  
Juan Burrone
Keyword(s):  
Action Potential ◽  
Hippocampal Neurons ◽  
Initial Segment ◽  
Pyramidal Neurons ◽  
Neuronal Cell ◽  
Axon Initial Segment ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Auditory Nucleus

The axon initial segment (AIS) is a structure at the start of the axon with a high density of sodium and potassium channels that defines the site of action potential generation. It has recently been shown that this structure is plastic and can change its position along the axon, as well as its length, in a homeostatic manner. Chronic activity-deprivation paradigms in a chick auditory nucleus lead to a lengthening of the AIS and an increase in neuronal excitability. On the other hand, a long-term increase in activity in dissociated rat hippocampal neurons results in an outward movement of the AIS and a decrease in the cell’s excitability. Here, we investigated whether the AIS is capable of undergoing structural plasticity in rat hippocampal organotypic slices, which retain the diversity of neuronal cell types present at postnatal ages, including chandelier cells. These interneurons exclusively target the AIS of pyramidal neurons and form rows of presynaptic boutons along them. Stimulating individual CA1 pyramidal neurons that express channelrhodopsin-2 for 48 h leads to an outward shift of the AIS. Intriguingly, both the pre- and postsynaptic components of the axo-axonic synapses did not change position after AIS relocation. We used computational modeling to explore the functional consequences of this partial mismatch and found that it allows the GABAergic synapses to strongly oppose action potential generation, and thus downregulate pyramidal cell excitability. We propose that this spatial arrangement is the optimal configuration for a homeostatic response to long-term stimulation.

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