Synaptic input and ACh modulation regulate dendritic Ca2+ spike duration in pyramidal neurons, directly affecting their somatic output

2021 ◽  
pp. JN-RM-1470-21
Author(s):  
Amir Dudai ◽  
Michael Doron ◽  
Idan Segev ◽  
Michael London
Keyword(s):  
Synaptic Input ◽  
Pyramidal Neurons

scholarly journals Increased Signal Delays and Unaltered Synaptic Input Pattern Recognition in Layer III Neocortical Pyramidal Neurons of the rTg4510 Mouse Model of Tauopathy: A Computer Simulation Study With Passive Membrane

2021 ◽  
Vol 15 ◽  
Author(s):  
Attila Somogyi ◽  
Ervin Wolf
Keyword(s):  
Pattern Recognition ◽  
Tau Protein ◽  
Synaptic Input ◽  
Pyramidal Neurons ◽  
Signal Propagation ◽  
Input Pattern ◽  
Tau Proteins ◽  
Chromosome 17 ◽  
Neuronal Membrane ◽  
Excitatory Postsynaptic Potential

Abnormal tau proteins are involved in pathology of many neurodegenerative disorders. Transgenic rTg4510 mice express high levels of human tau protein with P301L mutation linked to chromosome 17 that has been associated with frontotemporal dementia with parkinsonism. By 9 months of age, these mice recapitulate key features of human tauopathies, including presence of hyperphosphorylated tau and neurofibrillary tangles (NFTs) in brain tissue, atrophy and loss of neurons and synapses, and hyperexcitability of neurons, as well as cognitive deficiencies. We investigated effects of such human mutant tau protein on neuronal membrane, subthreshold dendritic signaling, and synaptic input pattern recognition/discrimination in layer III frontal transgenic (TG) pyramidal neurons of 9-month-old rTg4510 mice and compared these characteristics to those of wild-type (WT) pyramidal neurons from age-matched control mice. Passive segmental cable models of WT and TG neurons were set up in the NEURON simulator by using three-dimensionally reconstructed morphology and electrophysiological data of these cells. Our computer simulations predict leakage resistance and capacitance of neuronal membrane to be unaffected by the mutant tau protein. Computer models of TG neurons showed only modest alterations in distance dependence of somatopetal voltage and current transfers along dendrites and in rise times and half-widths of somatic Excitatory Postsynaptic Potential (EPSPs) relative to WT control. In contrast, a consistent and statistically significant slowdown was detected in the speed of simulated subthreshold dendritic signal propagation in all regions of the dendritic surface of mutant neurons. Predictors of synaptic input pattern recognition/discrimination remained unaltered in model TG neurons. This suggests that tau pathology is primarily associated with failures/loss in synaptic connections rather than with altered intraneuronal synaptic integration in neurons of affected networks.

scholarly journals Cannabinoids attenuate hippocampal gamma oscillations by suppressing excitatory synaptic input onto CA3 pyramidal neurons and fast spiking basket cells

2011 ◽  
Vol 589 (20) ◽  
pp. 4921-4934 ◽  
Author(s):  
Noémi Holderith ◽  
Beáta Németh ◽  
Orsolya I. Papp ◽  
Judit M. Veres ◽  
Gergő A. Nagy ◽  
...  
Keyword(s):  
Synaptic Input ◽  
Pyramidal Neurons ◽  
Gamma Oscillations ◽  
Basket Cells ◽  
Excitatory Synaptic Input ◽  
Fast Spiking ◽  
Ca3 Pyramidal Neurons

Dendritic Mechanisms of Phase Precession in Hippocampal CA1 Pyramidal Neurons

2001 ◽  
Vol 86 (1) ◽  
pp. 528-532 ◽  
Author(s):  
Jeffrey C. Magee
Keyword(s):  
Synaptic Input ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Sine Wave ◽  
Perforant Path ◽  
Adult Rats ◽  
Temporal Shift ◽  
Ca1 Pyramidal Neurons ◽  
Phase Precession ◽  
Voltage Gated Ion Channels

Dual whole-cell patch clamp recordings from the soma and dendrites of CA1 pyramidal neurons located in hippocampal slices of adult rats were used to examine the potential mechanisms of phase precession. To mimic phasic synaptic input, 5-Hz sine wave current injections were simultaneously delivered both to the soma and apical dendrites (dendritic current was 180° out-of-phase with soma). Increasing the amplitude of the dendritic current injection caused somatic action potential initiation to advance in time (move forward up to 180°). The exact pattern of phase advancement is dependent on the dendritic location of input, with more distal input causing a more gradual temporal shift in spike initiation and a smaller increase in spike number. Patterned stimulation of Schaffer collateral/perforant path synaptic input can produce phase precession that is very similar to that observed with sine wave current injections. Finally, the exact amount of synaptic input required to produce phase advancement was found to be regulated by dendritic voltage-gated ion channels. Together, these data demonstrate that the summation of primarily proximal inhibition with an increasing amount of out-of-phase, primarily distal excitation can result in a form of phase advancement similar to that seen during theta activity in the intact hippocampus.

scholarly journals Robustness of sensory-evoked excitation is increased by inhibitory inputs to distal apical tuft dendrites

2015 ◽  
Vol 112 (45) ◽  
pp. 14072-14077 ◽  
Author(s):  
Robert Egger ◽  
Arno C. Schmitt ◽  
Damian J. Wallace ◽  
Bert Sakmann ◽  
Marcel Oberlaender ◽  
...  
Keyword(s):  
Synaptic Input ◽  
Pyramidal Neurons ◽  
Barrel Cortex ◽  
Cell Types ◽  
Cortical Layer ◽  
Evoked Responses ◽  
Apical Tuft ◽  
Sensory Evoked ◽  
Pharmacological Manipulations

Cortical inhibitory interneurons (INs) are subdivided into a variety of morphologically and functionally specialized cell types. How the respective specific properties translate into mechanisms that regulate sensory-evoked responses of pyramidal neurons (PNs) remains unknown. Here, we investigated how INs located in cortical layer 1 (L1) of rat barrel cortex affect whisker-evoked responses of L2 PNs. To do so we combined in vivo electrophysiology and morphological reconstructions with computational modeling. We show that whisker-evoked membrane depolarization in L2 PNs arises from highly specialized spatiotemporal synaptic input patterns. Temporally L1 INs and L2–5 PNs provide near synchronous synaptic input. Spatially synaptic contacts from L1 INs target distal apical tuft dendrites, whereas PNs primarily innervate basal and proximal apical dendrites. Simulations of such constrained synaptic input patterns predicted that inactivation of L1 INs increases trial-to-trial variability of whisker-evoked responses in L2 PNs. The in silico predictions were confirmed in vivo by L1-specific pharmacological manipulations. We present a mechanism—consistent with the theory of distal dendritic shunting—that can regulate the robustness of sensory-evoked responses in PNs without affecting response amplitude or latency.

scholarly journals Lineage does not regulate the sensory synaptic input of projection neurons in the mouse olfactory bulb

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Luis Sánchez-Guardado ◽  
Carlos Lois
Keyword(s):  
Olfactory Bulb ◽  
Sensory Neurons ◽  
Synaptic Input ◽  
Pyramidal Neurons ◽  
Cell Lineage ◽  
Olfactory Receptors ◽  
Projection Neurons ◽  
Olfactory Sensory Neurons ◽  
Neuronal Progenitors ◽  
Functional Relevance

Lineage regulates the synaptic connections between neurons in some regions of the invertebrate nervous system. In mammals, recent experiments suggest that cell lineage determines the connectivity of pyramidal neurons in the neocortex, but the functional relevance of this phenomenon and whether it occurs in other neuronal types remains controversial. We investigated whether lineage plays a role in the connectivity of mitral and tufted cells, the projection neurons in the mouse olfactory bulb. We used transgenic mice to sparsely label neuronal progenitors and observed that clonally related neurons receive synaptic input from olfactory sensory neurons expressing different olfactory receptors. These results indicate that lineage does not determine the connectivity between olfactory sensory neurons and olfactory bulb projection neurons.

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 Heterogeneous Firing Responses Predict Diverse Couplings to Presynaptic Activity in mice Layer V Pyramidal Neurons

2016 ◽  
Author(s):  
Yann Zerlaut ◽  
Alain Destexhe
Keyword(s):  
Membrane Potential ◽  
Synaptic Input ◽  
Pyramidal Neurons ◽  
Network Activity ◽  
Local Network ◽  
Potential Fluctuations ◽  
Branching Rule ◽  
Layer V ◽  
Different Levels ◽  
Membrane Potential Fluctuations

In this study, we present a theoretical framework combining experimental characterizations and analytical calculus to capture the firing rate input-output properties of single neurons in the fluctuation-driven regime. Our framework consists of a two-step procedure to treat independently how the dendritic input translates into somatic fluctuation variables, and how the latter determine action potential firing. We use this framework to investigate the functional impact of the heterogeneity in firing responses found experimentally in young mice layer V pyramidal cells. We first design and calibrate in vitro a simplified morphological model of layer V pyramidal neurons with a dendritic tree following Rall's branching rule. Then, we propose an analytical derivation for the membrane potential fluctuations at the soma as a function of the properties of the synaptic input in dendrites. This mathematical description allows us to easily emulate various forms of synaptic input: either balanced, unbalanced, synchronized, purely proximal or purely distal synaptic activity. We find that those different forms of input activity lead to various impact on the membrane potential fluctuations properties, thus raising the possibility that individual neurons will differentially couple to specific forms of activity as a result of their different firing response. We indeed found such a heterogeneous coupling between synaptic input and firing response for all types of presynaptic activity. This heterogeneity can be explained by different levels of cellular excitability in the case of the balanced, unbalanced, synchronized and purely distal activity. A notable exception appears for proximal dendritic inputs: increasing the input level can either promote firing response in some cells, or suppress it in some other cells whatever their individual excitability. This behavior can be explained by different sensitivities to the speed of the fluctuations, which was previously associated to different levels of sodium channel inactivation and density. Because local network connectivity rather targets proximal dendrites, our results suggest that this aspect of biophysical heterogeneity might be relevant to neocortical processing by controlling how individual neurons couple to local network activity.

Amplification of EPSPs by Low Ni2+- and Amiloride-Sensitive Ca2+ Channels in Apical Dendrites of Rat CA1 Pyramidal Neurons

1997 ◽  
Vol 77 (3) ◽  
pp. 1639-1643 ◽  
Author(s):  
Thomas Gillessen ◽  
Christian Alzheimer
Keyword(s):  
Membrane Potential ◽  
Synaptic Input ◽  
Pyramidal Neurons ◽  
Low Voltage ◽  
Stratum Radiatum ◽  
Excitatory Postsynaptic Potential ◽  
Appreciable Effect ◽  
Epsp Amplitude ◽  
Ca1 Pyramidal Neurons ◽  
Apical Dendrites

Gillessen, Thomas and Christian Alzheimer. Amplification of EPSPs by low Ni2+- and amiloride-sensitive Ca2+ channels in apical dendrites of rat CA1 pyramidal neurons. J. Neurophysiol. 77: 1639–1643, 1997. Distal synaptic input to hippocampal CA1 pyramidal neurons was evoked by electrical stimulation of afferent fibers in outer stratum radiatum. Whole cell recordings from CA1 cell somata served to monitor excitatory postsynaptic potential (EPSP) envelopes after dendritic processing. To probe a functional role of low-voltage-activated Ca2+ current [or T current ( I T)] in the apical dendrite, EPSP recordings were combined with local application of antagonists of I T. Dendritic application of low concentrations of Ni2+ (5 μM) and amiloride (50 μM) reduced EPSP amplitude measured at the soma (resting membrane potential −70 mV) by 33.0 ± 2.9% (mean ± SE, n = 27) and 27.0 ± 2.1%( n = 26), respectively. No appreciable effect on EPSP time course was observed. As expected from the voltage dependence of I T activation, the inhibitory effect of both antagonists was strongly attenuated when EPSPs were recorded at hyperpolarized membrane potential (−90 mV). In contrast to dendritic application, somatic application of Ni2+ or amiloride produced only weak reduction of EPSP amplitude. Our data indicate that dendritic low Ni2+- and amiloride-sensitive Ca2+ channels giving rise predominantly to I T can produce substantial amplification of synaptic input. We thus propose that these channels represent an important component of subthreshold signal integration in apical dendrites of CA1 pyramidal cells.

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