scholarly journals Diversity amongst human cortical pyramidal neurons revealed via their sag currents and frequency preferences

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Homeira Moradi Chameh ◽  
Scott Rich ◽  
Lihua Wang ◽  
Fu-Der Chen ◽  
Liang Zhang ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Theta Oscillations ◽  
Cortical Layers ◽  
Electrophysiological Properties ◽  
Theta Frequency ◽  
Subthreshold Resonance ◽  
Cortical Pyramidal Neurons ◽  
Whole Cell Recordings

AbstractIn the human neocortex coherent interlaminar theta oscillations are driven by deep cortical layers, suggesting neurons in these layers exhibit distinct electrophysiological properties. To characterize this potential distinctiveness, we use in vitro whole-cell recordings from cortical layers 2 and 3 (L2&3), layer 3c (L3c) and layer 5 (L5) of the human cortex. Across all layers we observe notable heterogeneity, indicating human cortical pyramidal neurons are an electrophysiologically diverse population. L5 pyramidal cells are the most excitable of these neurons and exhibit the most prominent sag current (abolished by blockade of the hyperpolarization activated cation current, Ih). While subthreshold resonance is more common in L3c and L5, we rarely observe this resonance at frequencies greater than 2 Hz. However, the frequency dependent gain of L5 neurons reveals they are most adept at tracking both delta and theta frequency inputs, a unique feature that may indirectly be important for the generation of cortical theta oscillations.

scholarly journals Sag currents are a major contributor to human pyramidal cell intrinsic differences across cortical layers

2019 ◽  
Author(s):  
Homeira Moradi Chameh ◽  
Scott Rich ◽  
Lihua Wang ◽  
Fu-Der Chen ◽  
Liang Zhang ◽  
...  
Keyword(s):  
Deep Layer ◽  
Pyramidal Cells ◽  
Theta Oscillations ◽  
Cortical Layers ◽  
Electrophysiological Properties ◽  
Human Neocortex ◽  
Cation Current ◽  
Subthreshold Resonance ◽  
Whole Cell Recordings

AbstractIn the human neocortex, coherent theta (∼8Hz) oscillations between superficial and deep cortical layers are driven by deep layer neurons, suggesting distinct intrinsic electrophysiological properties of L5 neurons. We used in vitro whole-cell recordings to characterize pyramidal cells in layer 2/3 (L2/3), layer 3c (L3c) and layer 5 (L5) of the human neocortex. L5 pyramidal cells were more excitable and had a more prominent sag relative to L2/3 and L3c neurons that was abolished by blockade of the hyperpolarization activated cation current (Ih). We found a greater proportion of L5 and L3c neurons displaying subthreshold resonance relative to L2/3. Although no theta subthreshold resonance was observed in either L5 and L2/3 neurons, L5 neurons were more adept at tracking both delta (4Hz) and theta oscillations, the former being dependent on Ih. The unique features of human L5 neurons likely contribute to the emergence of theta oscillations in human cortical microcircuits.

scholarly journals Optimizing computer models of corticospinal neurons to replicate in vitro dynamics

2017 ◽  
Vol 117 (1) ◽  
pp. 148-162 ◽  
Author(s):  
Samuel A. Neymotin ◽  
Benjamin A. Suter ◽  
Salvador Dura-Bernal ◽  
Gordon M. G. Shepherd ◽  
Michele Migliore ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Pyramidal Neurons ◽  
Computer Models ◽  
Cortical Layer ◽  
Cortical Layers ◽  
Electrophysiological Properties ◽  
Full Reconstruction ◽  
Resonance Properties ◽  
Oscillation Frequencies

Corticospinal neurons (SPI), thick-tufted pyramidal neurons in motor cortex layer 5B that project caudally via the medullary pyramids, display distinct class-specific electrophysiological properties in vitro: strong sag with hyperpolarization, lack of adaptation, and a nearly linear frequency-current ( F– I) relationship. We used our electrophysiological data to produce a pair of large archives of SPI neuron computer models in two model classes: 1) detailed models with full reconstruction; and 2) simplified models with six compartments. We used a PRAXIS and an evolutionary multiobjective optimization (EMO) in sequence to determine ion channel conductances. EMO selected good models from each of the two model classes to form the two model archives. Archived models showed tradeoffs across fitness functions. For example, parameters that produced excellent F– I fit produced a less-optimal fit for interspike voltage trajectory. Because of these tradeoffs, there was no single best model but rather models that would be best for particular usages for either single neuron or network explorations. Further exploration of exemplar models with strong F– I fit demonstrated that both the detailed and simple models produced excellent matches to the experimental data. Although dendritic ion identities and densities cannot yet be fully determined experimentally, we explored the consequences of a demonstrated proximal to distal density gradient of Ih, demonstrating that this would lead to a gradient of resonance properties with increased resonant frequencies more distally. We suggest that this dynamical feature could serve to make the cell particularly responsive to major frequency bands that differ by cortical layer. NEW & NOTEWORTHY We developed models of motor cortex corticospinal neurons that replicate in vitro dynamics, including hyperpolarization-induced sag and realistic firing patterns. Models demonstrated resonance in response to synaptic stimulation, with resonance frequency increasing in apical dendrites with increasing distance from soma, matching the increasing oscillation frequencies spanning deep to superficial cortical layers. This gradient may enable specific corticospinal neuron dendrites to entrain to relevant oscillations in different cortical layers, contributing to appropriate motor output commands.

Acute Clozapine Suppresses Synchronized Pyramidal Synaptic Network Activity by Increasing Inhibition in the Ferret Prefrontal Cortex

2007 ◽  
Vol 97 (2) ◽  
pp. 1196-1208 ◽  
Author(s):  
Wen-Jun Gao
Keyword(s):  
Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Suppressive Effect ◽  
Network Activity ◽  
Cortical Circuitry ◽  
Prefrontal Cortical ◽  
Recurrent Excitation ◽  
Whole Cell Recordings

Recent studies have indicated that impaired neural circuitry in the prefrontal cortex is a prominent feature of the neuropathology of schizophrenia. Clozapine is one of the most effective antipsychotic drugs used for this debilitating disease. Despite its effectiveness, the mechanism by which clozapine acts on prefrontal cortical circuitry remains poorly understood. In this study, in vitro multiple whole cell recordings were performed in slices of the ferret prefrontal cortex. Clozapine, which effectively inhibited the spontaneous synchronized network activities in the prefrontal neurons, achieved the suppressive effect by decreasing the recurrent excitation among pyramidal neurons and by enhancing the inhibitory inputs onto pyramidal cells through a likely network mechanism. Indeed, under the condition of disinhibition, the depressing effects were reversed and clozapine enhanced the recurrent excitation. These results suggest that the therapeutic actions of clozapine in alleviating the positive symptoms of schizophrenia are achieved, at least partially, through the readjustment of synaptic balance between the excitation and inhibition in the prefrontal cortical circuitry.

Differential Impact of Miniature Synaptic Potentials on the Soma and Dendrites of Pyramidal Neurons In Vivo

1997 ◽  
Vol 78 (3) ◽  
pp. 1735-1739 ◽  
Author(s):  
Denis Paré ◽  
Elen Lebel ◽  
Eric J. Lang
Keyword(s):  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Input Resistance ◽  
Differential Impact ◽  
Synaptic Potentials ◽  
Ampa Antagonists ◽  
Intact Brain ◽  
The Impact

Paré, Denis, Elen LeBel, and Eric J. Lang. Differential impact of miniature synaptic potentials on the somata and dendrites of pyramidal neurons in vivo. J. Neurophysiol. 78: 1735–1739, 1997. We studied the impact of transmitter release resistant to tetrodotoxin (TTX) in morphologically identified neocortical pyramidal neurons recorded intracellularly in barbiturate-anesthetized cats. It was observed that TTX-resistant release occurs in pyramidal neurons in vivo and at much higher frequencies than was previously reported in vitro. Further, in agreement with previous findings indicating that GABAergic and glutamatergic synapses are differentially distributed in the somata and dendrites of pyramidal cells, we found that most miniature synaptic potentials were sensitive to γ-aminobutyric acid-A (GABAA) or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonists in presumed somatic and dendritic impalements, respectively. Pharmacological blockage of spontaneous synaptic events produced large increases in input resistance that were more important in dendritic (≈50%) than somatic (≈10%) impalements. These findings imply that in the intact brain, pyramidal neurons are submitted to an intense spike-independent synaptic bombardment that decreases the space constant of the cells. These results should be taken into account when extrapolating in vitro findings to intact brains.

scholarly journals Optogenetic activation of SST-positive interneurons restores hippocampal theta oscillation impairment induced by soluble amyloid beta oligomersin vivo

2018 ◽  
Author(s):  
Hyowon Chung ◽  
Kyerl Park ◽  
Hyun Jae Jang ◽  
Michael M Kohl ◽  
Jeehyun Kwag
Keyword(s):  
Learning And Memory ◽  
Peak Power ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Theta Oscillations ◽  
Ca1 Pyramidal Neurons ◽  
Theta Frequency ◽  
Hippocampal Theta

AbstractAbnormal accumulation of amyloid β oligomers (AβO) is a hallmark of Alzheimer’s disease (AD), which leads to learning and memory deficits. Hippocampal theta oscillations that are critical in spatial navigation, learning and memory are impaired in AD. Since GABAergic interneurons, such as somatostatin-positive (SST+) and parvalbumin-positive (PV+) interneurons, are believed to play key roles in the hippocampal oscillogenesis, we asked whether AβO selectively impairs these SST+ and PV+ interneurons. To selectively manipulate SST+ or PV+ interneuron activity in mice with AβO pathologyin vivo, we co-injected AβO and adeno-associated virus (AAV) for expressing floxed channelrhodopsin-2 (ChR2) into the hippocampus of SST-Cre or PV-Cre mice. Local field potential (LFP) recordingsin vivoin these AβO–injected mice showed a reduction in the peak power of theta oscillations and desynchronization of spikes from CA1 pyramidal neurons relative to theta oscillations compared to those in control mice. Optogenetic-activation of SST+ but not PV+ interneurons in AβO–injected mice fully restored the peak power of theta oscillations and resynchronized the theta spike phases to a level observed in control mice.In vitrowhole-cell voltage-clamp recordings in CA1 pyramidal neurons in hippocampal slices treated with AβO revealed that short-term plasticity of SST+ interneuron inhibitory inputs to CA1 pyramidal neurons at theta frequency were selectively disrupted while that of PV+ interneuron inputs were unaffected. Together, our results suggest that dysfunction in inputs from SST+ interneurons to CA1 pyramidal neurons may underlie the impairment of theta oscillations observed in AβO-injected micein vivo.Our findings identify SST+ interneurons as a target for restoring theta-frequency oscillations in early AD.

scholarly journals Self-tuning of inhibition by endocannabinoids shapes spike-time precision in CA1 pyramidal neurons

2013 ◽  
Vol 110 (8) ◽  
pp. 1930-1944 ◽  
Author(s):  
Franck Dubruc ◽  
David Dupret ◽  
Olivier Caillard
Keyword(s):  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Memory Formation ◽  
Spike Timing ◽  
Excitatory Postsynaptic Potential ◽  
Spike Time ◽  
Transient Improvement ◽  
Self Tuning ◽  
Feedforward Inhibition

In the hippocampus, activity-dependent changes of synaptic transmission and spike-timing coordination are thought to mediate information processing for the purpose of memory formation. Here, we investigated the self-tuning of intrinsic excitability and spiking reliability by CA1 hippocampal pyramidal cells via changes of their GABAergic inhibitory inputs and endocannabinoid (eCB) signaling. Firing patterns of CA1 place cells, when replayed in vitro, induced an eCB-dependent transient reduction of spontaneous GABAergic activity, sharing the main features of depolarization-induced suppression of inhibition (DSI), and conditioned a transient improvement of spike-time precision during consecutive burst discharges. When evaluating the consequences of DSI on excitatory postsynaptic potential (EPSP)-spike coupling, we found that transient reductions of uncorrelated (spontaneous) or correlated (feedforward) inhibition improved EPSP-spike coupling probability. The relationship between EPSP-spike-timing reliability and inhibition was, however, more complex: transient reduction of correlated (feedforward) inhibition disrupted or improved spike-timing reliability according to the initial spike-coupling probability. Thus eCB-mediated tuning of pyramidal cell spike-time precision is governed not only by the initial level of global inhibition, but also by the ratio between spontaneous and feedforward GABAergic activities. These results reveal that eCB-mediated self-tuning of spike timing by the discharge of pyramidal cells can constitute an important contribution to place-cell assemblies and memory formation in the hippocampus.

scholarly journals Electrophysiological Diversity of Layer 5 Pyramidal Cells in the Prefrontal Cortex of the Rhesus Monkey: In Vitro Slice Studies

2007 ◽  
Vol 98 (5) ◽  
pp. 2622-2632 ◽  
Author(s):  
Yu-Ming Chang ◽  
Jennifer I. Luebke
Keyword(s):  
Prefrontal Cortex ◽  
Rhesus Monkey ◽  
Spike Train ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Dendritic Morphology ◽  
Firing Patterns ◽  
Electrophysiological Properties ◽  
Whole Cell Patch Clamp

Whole cell patch-clamp recordings were employed to characterize the electrophysiological properties of layer 5 pyramidal cells in slices of the prefrontal cortex (Area 46) of the rhesus monkey. Four electrophysiologically distinct cell types were discriminated based on distinctive repetitive action potential (AP) firing patterns and single AP characteristics: regular-spiking slowly adapting type-1 cells (RS1; 62%), regular-spiking slowly adapting type-2 cells (RS2; 18%), regular-spiking fast-adapting cells (FA; 15%), and intrinsically bursting cells (IB; 5%). These cells did not differ with regard to their location in layer 5 nor in their dendritic morphology. In RS1 cells, AP threshold and amplitude did not change significantly during a 2-s spike train, whereas in RS2 and FA cells, AP threshold increased significantly and AP amplitude decreased significantly during the train. In FA cells, complete adaptation of AP firing was observed within 600 ms. IB cells displayed an all-or-none burst of three to six APs, followed by RS1-type firing behavior. RS1 cells could be further subdivided into three subtypes. Low-threshold spiking (LTS) RS1 cells exhibited an initial doublet riding on a depolarizing potential at the onset of a spike train and a prominent depolarizing afterpotential (DAP); intermediate RS1 cells (IM) exhibited a DAP, but no initial doublet, and non-LTS RS1 cells exhibited neither a DAP nor an initial doublet. RS2 and FA cells did not exhibit a DAP or initial doublets. The distinctive firing patterns of these diverse layer 5 pyramidal cells may reflect different roles played by these cells in the mediation of subcortical neuronal activity by the dorsolateral PFC.

Axon terminal hyperexcitability associated with epileptogenesis in vitro. I. Origin of ectopic spikes

1993 ◽  
Vol 70 (3) ◽  
pp. 961-975 ◽  
Author(s):  
S. F. Stasheff ◽  
M. Hines ◽  
W. A. Wilson
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Model Neuron ◽  
Extracellular Recording ◽  
Pyramidal Cells ◽  
Initiation Site ◽  
Electrographic Seizures ◽  
Ca3 Pyramidal Cells

1. Intracellular and extracellular recording techniques were used to study the increase in ectopic (i.e., nonsomatic) action-potential generation occurring among CA3 pyramidal cells during the kindling-like induction of electrographic seizures (EGSs) in this subpopulation of the hippocampal slice. Kindling-like stimulus trains (60 Hz, 2 s) were delivered to s. radiatum of CA3 at 10-min intervals. As EGSs developed, the frequency of ectopic firing increased markedly (by 10.33 +/- 3.29 spikes/min, mean +/- SE, P << 0.01). Several methods were applied to determine the initiation site for these action potentials within the cell (axons vs. dendrites). 2. Collision tests were conducted between known antidromic and orthodromic action potentials in CA3 cells to determine the critical period, c, for collision. Attempts were then made to collide ectopic spikes with known antidromic action potentials. At intervals less than c, ectopic spikes failed to collide with antidromic ones, in 5 of 10 cases. In these cells, this clearly indicates that the ectopic spikes were themselves of axonal origin. In the remaining five cases, ectopic spikes collided with antidromic action potentials at intervals approximately equal to c, most likely because of interactions within the complex system of recurrent axon collaterals in CA3. 3. Action potentials of CA3 pyramidal cells were simulated with the use of a compartmental computer model, NEURON. These simulations were based on prior models of CA3 pyramidal neurons and of the motoneuron action potential. Simulated action potentials generated in axonal compartments possessed a prominent inflection on their rising phase (IS-SD break), which was difficult to appreciate in those spikes generated in somatic or dendritic compartments. 4. An analysis of action potentials recorded experimentally from CA3 pyramidal cells also showed that antidromic spikes possess a prominent IS-SD break that is not present in orthodromic spikes. In addition to identified antidromic action potentials, ectopic spikes also possess such an inflection. Together with the predictions of computer simulations, this analysis also indicates that ectopic spikes originate in the axons of CA3 cells. 5. Tetrodotoxin (TTX, 50 microM) was locally applied by pressure injection while monitoring ectopic spike activity. Localized application of TTX to regions of the slice that could include the axons but not the dendrites of recorded cells abolished or markedly reduced the frequency of ectopic spikes (n = 5), further confirming the hypothesis that these action potentials arise from CA3 axons.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Maturation of Intrinsic and Synaptic Properties of Layer 2/3 Pyramidal Neurons in Mouse Auditory Cortex

2008 ◽  
Vol 99 (6) ◽  
pp. 2998-3008 ◽  
Author(s):  
Anne-Marie M. Oswald ◽  
Alex D. Reyes
Keyword(s):  
Auditory Processing ◽  
Pyramidal Neurons ◽  
Input Resistance ◽  
Transitional Period ◽  
Resting Membrane Potential ◽  
Neural Excitability ◽  
Age Related ◽  
Mean And Variance ◽  
Whole Cell Recordings

We investigated the development of L2/3 pyramidal cell (PC) circuitry in juvenile mice from postnatal day 10 (P10) to P29. Using whole cell recordings in an in vitro thalamocortical slice preparation, we examined the connection architecture and intrinsic and synaptic properties of PCs. The excitatory connections between PCs were highly localized: the probability of connection between PCs declined with intersomatic distance from 0.18 to about 0.05 over 150 μm, but did not vary with age. However, the mean and variance of the intrinsic and synaptic properties of PCs changed dramatically between P10 and P29. The input resistance, membrane time constant, and resting membrane potential decreased, leading to reduced neural excitability in older animals. Likewise, there were age-dependent decreases in the amplitude and decay time of the excitatory postsynaptic potentials as well as short-term synaptic depression. Both the intrinsic and synaptic properties underwent a transitional period between P10 and P18 prior to reaching steady state at P19–P29. We show that these properties combine to produce age-related differential synaptic responses to low- and high-frequency synaptic input that may contribute to differences in auditory processing during development.

Sign in / Sign up

Export Citation Format

Share Document