scholarly journals Local Glutamate-Mediated Dendritic Plateau Potentials Change the State of the Cortical Pyramidal Neuron

2019 ◽  
Author(s):  
Peng P. Gao ◽  
Joseph. W. Graham ◽  
Wen-Liang Zhou ◽  
Jinyoung Jang ◽  
Sergio Angulo ◽  
...  
Keyword(s):  
Cell Body ◽  
Cortical Neurons ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Basal Dendrite ◽  
Plateau Potentials ◽  
Prepared State ◽  
Cortical Pyramidal Neurons ◽  
Afferent Inputs

AbstractDendritic spikes in thin dendritic branches (basal and oblique dendrites) of pyramidal neurons are traditionally inferred from spikelets measured in the cell body. Here, we used laser-spot voltage-sensitive dye imaging in cortical pyramidal neurons (rat brain slices) to investigate the voltage waveforms of dendritic potentials occurring in response to spatially-restricted glutamatergic inputs. Local dendritic potentials lasted 200–500 ms and propagated to the cell body where they caused sustained 10-20 mV depolarizations. Plateau potentials propagating from dendrite to soma, and action potentials propagating from soma to dendrite, created complex voltage waveforms in the middle of the thin basal dendrite, comprised of local sodium spikelets, local plateau potentials, and back-propagating action potentials, superimposed on each other. Our model replicated these experimental observations and made predictions, which were tested in experiments. Dendritic plateau potentials occurring in basal and oblique branches put pyramidal neurons into an activated neuronal state (“prepared state”), characterized by depolarized membrane potential and faster membrane responses. The prepared state provides a time window of 200-500 ms during which cortical neurons are particularly excitable and capable of following afferent inputs. At the network level, this predicts that sets of cells with simultaneous plateaus would provide cellular substrate for the formation of functional neuronal ensembles.New & NoteworthyIn cortical pyramidal neurons, we recorded glutamate-mediated dendritic plateau potentials using voltage imaging, and created a computer model that recreated experimental measures from dendrite and cell body. Our model made new predictions, which were then tested in experiments. Plateau potentials profoundly change neuronal state -- a plateau potential triggered in one basal dendrite depolarizes the soma and shortens membrane time constant, making the cell more susceptible to firing triggered by other afferent inputs.

scholarly journals Local glutamate-mediated dendritic plateau potentials change the state of the cortical pyramidal neuron

2021 ◽  
Vol 125 (1) ◽  
pp. 23-42
Author(s):  
Peng P. Gao ◽  
Joseph W. Graham ◽  
Wen-Liang Zhou ◽  
Jinyoung Jang ◽  
Sergio Angulo ◽  
...  
Keyword(s):  
Time Constant ◽  
Computer Model ◽  
Pyramidal Neuron ◽  
Pyramidal Neurons ◽  
Basal Dendrite ◽  
Plateau Potentials ◽  
Voltage Imaging ◽  
Plateau Potential ◽  
Cortical Pyramidal Neurons ◽  
Afferent Inputs

In cortical pyramidal neurons, we recorded glutamate-mediated dendritic plateau potentials with voltage imaging and created a computer model that recreated experimental measures from dendrite and cell body. Our model made new predictions, which were then tested in experiments. Plateau potentials profoundly change neuronal state: a plateau potential triggered in one basal dendrite depolarizes the soma and shortens membrane time constant, making the cell more susceptible to firing triggered by other afferent inputs.

scholarly journals Spatiotemporally Graded NMDA Spike/Plateau Potentials in Basal Dendrites of Neocortical Pyramidal Neurons

2008 ◽  
Vol 99 (5) ◽  
pp. 2584-2601 ◽  
Author(s):  
Guy Major ◽  
Alon Polsky ◽  
Winfried Denk ◽  
Jackie Schiller ◽  
David W. Tank
Keyword(s):  
Decision Making ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Dynamic Decision Making ◽  
Spatial Gradient ◽  
Basal Dendrite ◽  
Plateau Potentials ◽  
Basal Dendrites ◽  
Cortical Pyramidal Neurons

Glutamatergic inputs clustered over ∼20–40 μm can elicit local N-methyl-d-aspartate (NMDA) spike/plateau potentials in terminal dendrites of cortical pyramidal neurons, inspiring the notion that a single terminal dendrite can function as a decision-making computational subunit. A typical terminal basal dendrite is ∼100–200 μm long: could it function as multiple decision-making subunits? We test this by sequential focal stimulation of multiple sites along terminal basal dendrites of layer 5 pyramidal neurons in rat somatosensory cortical brain slices, using iontophoresis or uncaging of brief glutamate pulses. There was an approximately sevenfold spatial gradient in average spike/plateau amplitude measured at the soma, from ∼3 mV for distal inputs to ∼23 mV for proximal inputs. Spike/plateaus were NMDA receptor (NMDAR) conductance-dominated at all locations. Large Ca2+ transients accompanied spike/plateaus over a ∼10- to 40-μm zone around the input site; smaller Ca2+ transients extended approximately uniformly to the dendritic tip. Spike/plateau duration grew with increasing glutamate and depolarization; high Ca2+ zone size grew with spike/plateau duration. The minimum high Ca2+ zone half-width (just above NMDA spike threshold) increased from distal (∼10 μm) to proximal locations (∼25 μm), as did the NMDA spike glutamate threshold. Depolarization reduced glutamate thresholds. Simulations exploring multi-site interactions based on this demonstrate that if appropriately timed and localized inputs occur in vivo, a single basal dendrite could correspond to a cascade of multiple co-operating dynamic decision-making subunits able to retain information for hundreds of milliseconds, with increasing influence on neural output from distal to proximal. Dendritic NMDA spike/plateaus are thus well-suited to support graded persistent firing.

Suppression of Ih Contributes to Propofol-Induced Inhibition of Mouse Cortical Pyramidal Neurons

2005 ◽  
Vol 94 (6) ◽  
pp. 3872-3883 ◽  
Author(s):  
Xiangdong Chen ◽  
Shaofang Shu ◽  
Douglas A. Bayliss
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Current Amplitude ◽  
Hcn Channels ◽  
General Anesthetic ◽  
Large Shift ◽  
Fast Kinetics ◽  
Membrane Hyperpolarization ◽  
Cortical Pyramidal Neurons

The contributions of the hyperpolarization-activated current, Ih, to generation of rhythmic activities are well described for various central neurons, particularly in thalamocortical circuits. In the present study, we investigated effects of a general anesthetic, propofol, on native Ih in neurons of thalamus and cortex and on the corresponding cloned HCN channel subunits. Whole cell voltage-clamp recordings from mouse brain slices identified neuronal Ih currents with fast activation kinetics in neocortical pyramidal neurons and with slower kinetics in thalamocortical relay cells. Propofol inhibited the fast-activating Ih in cortical neurons at a clinically relevant concentration (5 μM); inhibition of Ih involved a hyperpolarizing shift in half-activation voltage (Δ V1/2 approximately −9 mV) and a decrease in maximal available current (∼36% inhibition, measured at −120 mV). With the slower form of Ih expressed in thalamocortical neurons, propofol had no effect on current activation or amplitude. In heterologous expression systems, 5 μM propofol caused a large shift in V1/2 and decrease in current amplitude in homomeric HCN1 and linked heteromeric HCN1–HCN2 channels, both of which activate with fast kinetics but did not affect V1/2 or current amplitude of slowly activating homomeric HCN2 channels. With GABAA and glycine receptor channels blocked, propofol caused membrane hyperpolarization and suppressed action potential discharge in cortical neurons; these effects were occluded by the Ih blocker, ZD-7288. In summary, these data indicate that propofol selectively inhibits HCN channels containing HCN1 subunits, such as those that mediate Ih in cortical pyramidal neurons—and they suggest that anesthetic actions of propofol may involve inhibition of cortical neurons and perhaps other HCN1-expressing cells.

scholarly journals Implantable microcoils for intracortical magnetic stimulation

2016 ◽  
Vol 2 (12) ◽  
pp. e1600889 ◽  
Author(s):  
Seung Woo Lee ◽  
Florian Fallegger ◽  
Bernard D. F. Casse ◽  
Shelley I. Fried
Keyword(s):  
Cortical Neurons ◽  
Magnetic Stimulation ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Behavioral Responses ◽  
Wide Range ◽  
Cortical Pyramidal Neurons ◽  
Over Time

Neural prostheses that stimulate the neocortex have the potential to treat a wide range of neurological disorders. However, the efficacy of electrode-based implants remains limited, with persistent challenges that include an inability to create precise patterns of neural activity as well as difficulties in maintaining response consistency over time. These problems arise from fundamental limitations of electrodes as well as their susceptibility to implantation and have proven difficult to overcome. Magnetic stimulation can address many of these limitations, but coils small enough to be implanted into the cortex were not thought strong enough to activate neurons. We describe a new microcoil design and demonstrate its effectiveness for both activating cortical neurons and driving behavioral responses. The stimulation of cortical pyramidal neurons in brain slices in vitro was reliable and could be confined to spatially narrow regions (<60 μm). The spatially asymmetric fields arising from the coil helped to avoid the simultaneous activation of passing axons. In vivo implantation was safe and resulted in consistent and predictable behavioral responses. The high permeability of magnetic fields to biological substances may yield another important advantage because it suggests that encapsulation and other adverse effects of implantation will not diminish coil performance over time, as happens to electrodes. These findings suggest that a coil-based implant might be a useful alternative to existing electrode-based devices. The enhanced selectivity of microcoil-based magnetic stimulation will be especially useful for visual prostheses as well as for many brain-computer interface applications that require precise activation of the cortex.

scholarly journals Widely Different Correlation Patterns Between Pairs of Adjacent Thalamic Neurons In vivo

2021 ◽  
Vol 15 ◽  
Author(s):  
Anders Wahlbom ◽  
Hannes Mogensen ◽  
Henrik Jörntell
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Thalamic Nuclei ◽  
Thalamic Neurons ◽  
Low Weight ◽  
Afferent Inputs ◽  
Cortical Inputs ◽  
Unique Relationship ◽  
Spike Firing

We have previously reported different spike firing correlation patterns among pairs of adjacent pyramidal neurons within the same layer of S1 cortex in vivo, which was argued to suggest that acquired synaptic weight modifications would tend to differentiate adjacent cortical neurons despite them having access to near-identical afferent inputs. Here we made simultaneous single-electrode loose patch-clamp recordings from 14 pairs of adjacent neurons in the lateral thalamus of the ketamine-xylazine anesthetized rat in vivo to study the correlation patterns in their spike firing. As the synapses on thalamic neurons are dominated by a high number of low weight cortical inputs, which would be expected to be shared for two adjacent neurons, and as far as thalamic neurons have homogenous membrane physiology and spike generation, they would be expected to have overall similar spike firing and therefore also correlation patterns. However, we find that across a variety of thalamic nuclei the correlation patterns between pairs of adjacent thalamic neurons vary widely. The findings suggest that the connectivity and cellular physiology of the thalamocortical circuitry, in contrast to what would be expected from a straightforward interpretation of corticothalamic maps and uniform intrinsic cellular neurophysiology, has been shaped by learning to the extent that each pair of thalamic neuron has a unique relationship in their spike firing activity.

A Time-Dependent Excitability change in the soma of an identified Insect Motoneurone

1992 ◽  
Vol 162 (1) ◽  
pp. 251-263
Author(s):  
JULES C. HANCOX ◽  
ROBERT M. PITMAN
Keyword(s):  
Cell Body ◽  
Action Potentials ◽  
Periplaneta Americana ◽  
Channel Blocker ◽  
Time Dependent ◽  
Sodium Channel Blocker ◽  
Plateau Potentials ◽  
Excitability Change ◽  
Membrane Oscillations

Long-term, current-clamp recordings were made from the cell body of the fast coxal depressor motoneurone (Df) of the third thoracic ganglion of the cockroach Periplaneta americana. In freshly dissected preparations the response to shortduration, suprathreshold, depolarising current pulses was a graded series of damped membrane oscillations similar to those reported previously in this neurone. The response to current injection changed, however, with increasing time after setting up the preparation: cells developed the ability to exhibit all-ornone action potentials. Their amplitude, however, was usually insufficient to overshoot 0 m V. Our observations suggest that the enhancement in excitability is dependent on time following dissection rather than on time following impalement. Recordings taken from neurone somata mechanically divided from their processes indicated that the time-dependent changes in excitability were not attributable to changes in synaptic input to the neurone and, moreover, that the cell body was involved in action potential genesis. The action potentials were resistant to treatment with the sodium channel blocker tetrodotoxin (up to 10−5 mol l−1), but were reversibly abolished when preparations were bathed in saline containing cadmium ions (1 mmol l−1) or manganese ions (20 or 40 mmol l−1) and, therefore, the inward current underlying these events was largely, if not entirely, carried by calcium ions. These time-dependent action potentials can co-exist with plateau potentials. In neurones giving both plateau potentials and time-dependent action potentials, plateau potentials can drive action potentials in bursts.

Prolonged Synaptic Integration in Perirhinal Cortical Neurons

2000 ◽  
Vol 83 (6) ◽  
pp. 3294-3298 ◽  
Author(s):  
John M. Beggs ◽  
James R. Moyer ◽  
John P. McGann ◽  
Thomas H. Brown
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Perirhinal Cortex ◽  
Visually Guided ◽  
Time Intervals ◽  
Current Step ◽  
Long Time ◽  
Temporal Learning ◽  
Whole Cell Recordings

Layer II/III of rat perirhinal cortex (PR) contains numerous late-spiking (LS) pyramidal neurons. When injected with a depolarizing current step, these LS cells typically delay spiking for one or more seconds from the onset of the current step and then sustain firing for the duration of the step. This pattern of delayed and sustained firing suggested a specific computational role for LS cells in temporal learning. This hypothesis predicts and requires that some layer II/III neurons should also exhibit delayed and sustained spiking in response to a train of excitatory synaptic inputs. Here we tested this prediction using visually guided, whole cell recordings from rat PR brain slices. Most LS cells (19 of 26) exhibited delayed spiking to synaptic stimulation (>1 s latency from the train onset), and the majority of these cells (13 of 19) also showed sustained firing that persisted for the duration of the synaptic train (5–10 s duration). Delayed and sustained firing in response to long synaptic trains has not been previously reported in vertebrate neurons. The data are consistent with our model that a circuit containing late spiking neurons can be used for encoding long time intervals during associative learning.

scholarly journals Mechanisms underlying serotonergic excitation of callosal projection neurons

2017 ◽  
Author(s):  
Emily K. Stephens ◽  
Arielle L. Baker ◽  
Allan T. Gulledge
Keyword(s):  
Intracellular Calcium ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Projection Neurons ◽  
Calcium Dependent ◽  
M Current ◽  
Cation Conductance ◽  
Cortical Pyramidal Neurons ◽  
Excitatory Responses ◽  
Callosal Projection

AbstractSerotonin (5-HT) selectively excites subpopulations of pyramidal neurons in the neocortex via activation of 5-HT2A (2A) receptors coupled to Gq subtype G-protein alpha subunits. Gq-mediated excitatory responses have been attributed primarily to suppression of potassium conductances, including those mediated by KV7 potassium channels (i.e., the M-current), or activation of nonspecific cation conductances that underly calcium-dependent afterdepolarizations (ADPs). However, 2A-dependent excitation of cortical neurons has not been extensively studied, and no consensus exists regarding the underlying ionic effector(s) involved. We tested potential mechanisms of serotonergic excitation in commissural/callosal projection neurons (COM neurons) in layer 5 of the mouse medial prefrontal cortex, a subpopulation of cortical pyramidal neurons that exhibit 2A-dependent excitation in response to 5-HT. In baseline conditions, 5-HT enhanced the rate of action potential generation in COM neurons experiencing suprathreshold somatic current injection. This serotonergic excitation was occluded by activation of muscarinic acetylcholine (ACh) receptors, confirming that 5-HT acts via the same Gq-signaling cascades engaged by ACh. Like ACh, 5-HT promoted the generation of calcium-dependent ADPs following spike trains. However, calcium was not necessary for serotonergic excitation, as responses to 5-HT were enhanced (by >100%), rather than reduced, by chelation of intracellular calcium with 10 mM BAPTA. This suggests intracellular calcium negatively regulates additional ionic conductances contributing to 2A excitation. Removal of extracellular calcium had no effect when intracellular calcium signaling was intact, but suppressed 5-HT response amplitudes, by about 50% (i.e., back to normal baseline values) when BAPTA was included in patch pipettes. This suggests that 2A excitation involves activation of a nonspecific cation conductance that is both calcium-sensitive and calcium-permeable. M-current suppression was found to be a third ionic effector, as blockade of KV7 channels with XE991 (10 μM) reduced serotonergic excitation by ∼50% in control conditions, and by ∼30% with intracellular BAPTA present. These findings demonstrate a role for at least three distinct ionic effectors, including KV7 channels, a calcium-sensitive and calcium-permeable nonspecific cation conductance, and the calcium-dependent ADP conductance, in mediating serotonergic excitation of COM neurons.

scholarly journals Single Cortical Neurons as Deep Artificial Neural Networks

2019 ◽  
Author(s):  
David Beniaguev ◽  
Idan Segev ◽  
Michael London
Keyword(s):  
Neural Networks ◽  
Cortical Neurons ◽  
Deep Neural Networks ◽  
Pyramidal Neurons ◽  
Classical Architecture ◽  
Novel Approach ◽  
Cortical Pyramidal Neurons ◽  
Spatio Temporal ◽  
Cortical Pyramidal Cell

AbstractWe introduce a novel approach to study neurons as sophisticated I/O information processing units by utilizing recent advances in the field of machine learning. We trained deep neural networks (DNNs) to mimic the I/O behavior of a detailed nonlinear model of a layer 5 cortical pyramidal cell, receiving rich spatio-temporal patterns of input synapse activations. A Temporally Convolutional DNN (TCN) with seven layers was required to accurately, and very efficiently, capture the I/O of this neuron at the millisecond resolution. This complexity primarily arises from local NMDA-based nonlinear dendritic conductances. The weight matrices of the DNN provide new insights into the I/O function of cortical pyramidal neurons, and the approach presented can provide a systematic characterization of the functional complexity of different neuron types. Our results demonstrate that cortical neurons can be conceptualized as multi-layered “deep” processing units, implying that the cortical networks they form have a non-classical architecture and are potentially more computationally powerful than previously assumed.

scholarly journals Voltage-gated sodium channels in neocortical pyramidal neurons display Cole-Moore activation kinetics

2017 ◽  
Author(s):  
Mara Almog ◽  
Tal Barkai ◽  
Angelika Lampert ◽  
Alon Korngreen
Keyword(s):  
Action Potential ◽  
Sodium Channels ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Gating Mechanism ◽  
Cortical Pyramidal Neurons

AbstractExploring the properties of action potentials is a crucial step towards a better understanding of the computational properties of single neurons and neural networks. The voltage-gated sodium channel is a key player in action potential generation. A comprehensive grasp of the gating mechanism of this channel can shed light on the biophysics of action potential generation. Most models of voltage-gated sodium channels assume it obeys a concerted Hodgkin and Huxley kinetic gating scheme. Here we performed high resolution voltage-clamp experiments from nucleated patches extracted from the soma of layer 5 (L5) cortical pyramidal neurons in rat brain slices. We show that the gating mechanism does not follow traditional Hodgkin and Huxley kinetics and that much of the channel voltage-dependence is probably due to rapid closed-closed transitions that lead to substantial onset latency reminiscent of the Cole-Moore effect observed in voltage-gated potassium conductances. This may have key implications for the role of sodium channels in synaptic integration and action potential generation.

Sign in / Sign up

Export Citation Format

Share Document