Relationships Between Intracellular Calcium and Afterhyperpolarizations in Neocortical Pyramidal Neurons

2004 ◽  
Vol 91 (1) ◽  
pp. 324-335 ◽  
Author(s):  
H. J. Abel ◽  
J.C.F. Lee ◽  
J. C. Callaway ◽  
R. C. Foehring
Keyword(s):  
Intracellular Calcium ◽  
Linear Relationship ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Firing Frequency ◽  
Discharge Activity ◽  
Apical Dendrites ◽  
Neocortical Pyramidal Neurons

We examined the effects of recent discharge activity on [Ca2+]i in neocortical pyramidal cells. Our data confirm and extend the observation that there is a linear relationship between plateau [Ca2+]i and firing frequency in soma and proximal apical dendrites. The rise in [Ca2+] activates K+ channels underlying the afterhyperpolarization (AHP), which consists of 2 Ca2+-dependent components: the medium AHP (mAHP) and the slow AHP (sAHP). The mAHP is blocked by apamin, indicating involvement of SK-type Ca2+-dependent K+ channels. The identity of the apamin-insensitive sAHP channel is unknown. We compared the sAHP and the mAHP with regard to: 1) number and frequency of spikes versus AHP amplitude; 2) number and frequency of spikes versus [Ca2+]i; 3) IAHP versus [Ca2+]i. Our data suggest that sAHP channels require an elevation of [Ca2+]i in the cytoplasm, rather than at the membrane, consistent with a role for a cytoplasmic intermediate between Ca2+ and the K+ channels. The mAHP channels appear to respond to a restricted Ca2+ domain.

scholarly journals Evidence of calcium-permeable AMPA receptors in dendritic spines of CA1 pyramidal neurons

2014 ◽  
Vol 112 (2) ◽  
pp. 263-275 ◽  
Author(s):  
Hayley A. Mattison ◽  
Ashish A. Bagal ◽  
Michael Mohammadi ◽  
Nisha S. Pulimood ◽  
Christian G. Reich ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Ampa Receptors ◽  
Pyramidal Neurons ◽  
Calcium Influx ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Stratum Radiatum ◽  
Acute Hippocampal Slices ◽  
Cultured Slices ◽  
Apical Dendrites

GluA2-lacking, calcium-permeable α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPARs) have unique properties, but their presence at excitatory synapses in pyramidal cells is controversial. We have tested certain predictions of the model that such receptors are present in CA1 cells and show here that the polyamine spermine, but not philanthotoxin, causes use-dependent inhibition of synaptically evoked excitatory responses in stratum radiatum, but not s. oriens, in cultured and acute hippocampal slices. Stimulation of single dendritic spines by photolytic release of caged glutamate induced an N-methyl-d-aspartate receptor-independent, use- and spermine-sensitive calcium influx only at apical spines in cultured slices. Bath application of glutamate also triggered a spermine-sensitive influx of cobalt into CA1 cell dendrites in s. radiatum. Responses of single apical, but not basal, spines to photostimulation displayed prominent paired-pulse facilitation (PPF) consistent with use-dependent relief of cytoplasmic polyamine block. Responses at apical dendrites were diminished, and PPF was increased, by spermine. Intracellular application of pep2m, which inhibits recycling of GluA2-containing AMPARs, reduced apical spine responses and increased PPF. We conclude that some calcium-permeable, polyamine-sensitive AMPARs, perhaps lacking GluA2 subunits, are present at synapses on apical dendrites of CA1 pyramidal cells, which may allow distinct forms of synaptic plasticity and computation at different sets of excitatory inputs.

Fiberoptic System for Recording Dendritic Calcium Signals in Layer 5 Neocortical Pyramidal Cells in Freely Moving Rats

2007 ◽  
Vol 98 (3) ◽  
pp. 1791-1805 ◽  
Author(s):  
Masanori Murayama ◽  
Enrique Pérez-Garci ◽  
Hans-Rudolf Lüscher ◽  
Matthew E. Larkum
Keyword(s):  
Pyramidal Neurons ◽  
Calcium Influx ◽  
Signal To Noise Ratio ◽  
Pyramidal Cells ◽  
Cellular Mechanisms ◽  
Novel Approach ◽  
Specific Loading ◽  
Apical Dendrites

Calcium influx into the dendritic tufts of layer 5 neocortical pyramidal neurons modifies a number of important cellular mechanisms. It can trigger local synaptic plasticity and switch the firing properties from regular to burst firing. Due to methodological limitations, our knowledge about Ca2+ spikes in the dendritic tuft stems mostly from in vitro experiments. However, it has been speculated that regenerative Ca2+ events in the distal dendrites correlate with distinct behavioral states. Therefore it would be most desirable to be able to record these Ca2+ events in vivo, preferably in the behaving animal. Here, we present a novel approach for recording Ca2+ signals in the dendrites of populations of layer 5 pyramidal neurons in vivo, which ensures that all recorded fluorescence changes are due to intracellular Ca2+ signals in the apical dendrites. The method has two main features: 1) bolus loading of layer 5 with a membrane-permeant Ca2+ dye resulting in specific loading of pyramidal cell dendrites in the upper layers and 2) a fiberoptic cable attached to a gradient index lens and a prism reflecting light horizontally at 90° to the angle of the apical dendrites. We demonstrate that the in vivo signal-to-noise ratio recorded with this relatively inexpensive and easy-to-implement fiberoptic-based device is comparable to conventional camera-based imaging systems used in vitro. In addition, the device is flexible and lightweight and can be used for recording Ca2+ signals in the distal dendritic tuft of freely behaving animals.

scholarly journals Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Audrey J. Weber ◽  
Ashley B. Adamson ◽  
Kelsey M. Greathouse ◽  
Julia P. Andrade ◽  
Cameron D. Freeman ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Spine Density ◽  
Control Of Gene Expression ◽  
Spine Morphology ◽  
Dendritic Spine Morphology ◽  
Morphometry Analysis ◽  
Apical Dendrites

AbstractRho-associated kinase isoform 2 (ROCK2) is an attractive drug target for several neurologic disorders. A critical barrier to ROCK2-based research and therapeutics is the lack of a mouse model that enables investigation of ROCK2 with spatial and temporal control of gene expression. To overcome this, we generated ROCK2fl/fl mice. Mice expressing Cre recombinase in forebrain excitatory neurons (CaMKII-Cre) were crossed with ROCK2fl/fl mice (Cre/ROCK2fl/fl), and the contribution of ROCK2 in behavior as well as dendritic spine morphology in the hippocampus, medial prefrontal cortex (mPFC), and basolateral amygdala (BLA) was examined. Cre/ROCK2fl/fl mice spent reduced time in the open arms of the elevated plus maze and increased time in the dark of the light–dark box test compared to littermate controls. These results indicated that Cre/ROCK2fl/fl mice exhibited anxiety-like behaviors. To examine dendritic spine morphology, individual pyramidal neurons in CA1 hippocampus, mPFC, and the BLA were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. In dorsal CA1, Cre/ROCK2fl/fl mice displayed significantly increased thin spine density on basal dendrites and reduced mean spine head volume across all spine types on apical dendrites. In ventral CA1, Cre/ROCK2fl/fl mice exhibited significantly increased spine length on apical dendrites. Spine density and morphology were comparable in the mPFC and BLA between both genotypes. These findings suggest that neuronal ROCK2 mediates spine density and morphology in a compartmentalized manner among CA1 pyramidal cells, and that in the absence of ROCK2 these mechanisms may contribute to anxiety-like behaviors.

Muscarinic Inhibition of Persistent Na+ Current in Rat Neocortical Pyramidal Neurons

1998 ◽  
Vol 79 (3) ◽  
pp. 1579-1582 ◽  
Author(s):  
Thomas Mittmann ◽  
Christian Alzheimer
Keyword(s):  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Cholinergic Innervation ◽  
Voltage Range ◽  
Rat Neocortex ◽  
The Rich ◽  
Subthreshold Voltage ◽  
Whole Cell Recordings ◽  
Muscarinic Modulation ◽  
Neocortical Pyramidal Neurons

Mittmann, Thomas and Christian Alzheimer. Muscarinic inhibition of persistent Na+ current in rat neocortical pyramidal neurons. J. Neurophysiol. 79: 1579–1582, 1998. Muscarinic modulation of persistent Na+ current ( I NaP) was studied using whole cell recordings from acutely isolated pyramidal cells of rat neocortex. After suppression of Ca2+ and K+ currents, I NaP was evoked by slow depolarizing voltage ramps or by long depolarizing voltage steps. The cholinergic agonist, carbachol, produced an atropine-sensitive decrease of I NaP at all potentials. When applied at a saturating concentration (20 μM), carbachol reduced peak I NaP by 38% on average. Carbachol did not alter the voltage dependence of I NaP activation nor did it interfere with the slow inactivation of I NaP. Our data indicate that I NaP can be targeted by the rich cholinergic innervation of the neocortex. Because I NaP is activated in the subthreshold voltage range, cholinergic inhibition of this current would be particularly suited to modulate the electrical behavior of neocortical pyramidal cells below and near firing threshold.

Propagating dendritic action potential mediates synaptic transmission in CA1 pyramidal cells in situ

1990 ◽  
Vol 64 (5) ◽  
pp. 1429-1441 ◽  
Author(s):  
O. Herreras
Keyword(s):  
Pyramidal Neurons ◽  
Current Source ◽  
Maximum Amplitude ◽  
Pyramidal Cells ◽  
Distal Portion ◽  
Ca1 Pyramidal Cells ◽  
Basal Dendrites ◽  
Voltage Dependent ◽  
Speed Of Propagation ◽  
Apical Dendrites

1. The events leading to the Schaffer collateral-induced discharge of CA1 pyramidal neurons were investigated in the hippocampus of anesthetized rats by current source-density (CSD) analysis. 2. The earliest evoked currents detected shortly after a stimulus were a sink in the zone where synapses are known to be located (300-350 microns ventral to the somatic layer) flanked by two smaller sources in the distal portion of the apical dendrites and in the somatic layer. This synaptic sink (SyS) extended over 75-100 microns; it lasted for 15-20 ms, and it reached its maximum amplitude some milliseconds after the population spike (PS) and remained in the same location. Stimuli submaximal and supramaximal for evoking a PS yielded the same pattern of current distribution for the SyS. Presynaptic fiber volleys were not detected in these recordings. 3. During the rising phase of the SyS a second sink appeared in a more proximal portion of the apical dendrites. This late dendritic sink (LS) extended over 50-75 microns and was centered 100-150 microns ventral to the somatic layer. This proximal dendritic sink was of amplitude comparable with the SyS; it outlasted the latter and was not necessarily followed by a somatic PS. The LS was extinguished with the appearance of a PS, whereas the SyS persisted regardless of the presence of a PS. 4. After maximal stimuli the LS grew until it exceeded a threshold amplitude, and then, it started to move somatopetally as a continuously propagating sink (PrS). The average speed of propagation was approximately 0.2 m/s. In 0.5-0.7 ms the PrS reached the cell-body layer displacing the passive source that moved into the basal dendrites. The PrS then became the intensive sink corresponding to the main (negative) phase of the somatic PS. This was followed by the development of an active source in the soma layer, probably corresponding to the repolarization phase of the PS. 5. From these observations it appears that the LS and PrS are active dendritic responses. It may be inferred that, shortly after the synaptic currents enter the dendrites, depolarization of adjacent membranes causes the opening of low-threshold, voltage-dependent, slowly inactivating channels that generate the LS. If the depolarization resulting from the LS current is intense enough, another population of channels open that are also voltage-dependent but of higher threshold and faster inactivation.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Electrophysiological properties of genetically identified subtypes of layer 5 neocortical pyramidal neurons: Ca2+ dependence and differential modulation by norepinephrine

2015 ◽  
Vol 113 (7) ◽  
pp. 2014-2032 ◽  
Author(s):  
Dongxu Guan ◽  
William E. Armstrong ◽  
Robert C. Foehring
Keyword(s):  
Pyramidal Neurons ◽  
Fluorescent Protein ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Field Size ◽  
Repetitive Firing ◽  
Differential Modulation ◽  
Electrophysiological Properties ◽  
Laminar Distribution ◽  
Neocortical Pyramidal Neurons

We studied neocortical pyramidal neurons from two lines of bacterial artificial chromosome mice ( etv1 and glt; Gene Expression Nervous System Atlas: GENSAT project), each of which expresses enhanced green fluorescent protein (EGFP) in a different subpopulation of layer 5 pyramidal neurons. In barrel cortex, etv1 and glt pyramidal cells were previously reported to differ in terms of their laminar distribution, morphology, thalamic inputs, cellular targets, and receptive field size. In this study, we measured the laminar distribution of etv1 and glt cells. On average, glt cells were located more deeply; however, the distributions of etv1 and glt cells extensively overlap in layer 5. To test whether these two cell types differed in electrophysiological properties that influence firing behavior, we prepared acute brain slices from 2–4-wk-old mice, where EGFP-positive cells in somatosensory cortex were identified under epifluorescence and then studied using whole cell current- or voltage-clamp recordings. We studied the details of action potential parameters and repetitive firing, characterized by the larger slow afterhyperpolarizations (AHPs) in etv1 neurons and larger medium AHPs (mAHPS) in glt cells, and compared currents underlying the mAHP and slow AHP (sAHP) in etv1 and glt neurons. Etv1 cells exhibited lower d V/d t for spike polarization and repolarization and reduced direct current (DC) gain (lower f- I slope) for repetitive firing than glt cells. Most importantly, we found that 1) differences in the expression of Ca2+-dependent K+ conductances (small-conductance calcium-activated potassium channels and sAHP channels) determine major functional differences between etv1 and glt cells, and 2) there is differential modulation of etv1 and glt neurons by norepinephrine.

Mechanisms Underlying Burst and Regular Spiking Evoked by Dendritic Depolarization in Layer 5 Cortical Pyramidal Neurons

1999 ◽  
Vol 81 (3) ◽  
pp. 1341-1354 ◽  
Author(s):  
Peter Schwindt ◽  
Wayne Crill
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Critical Level ◽  
Pyramidal Cells ◽  
Burst Firing ◽  
Action Current ◽  
Constant Frequency ◽  
Functional Implications ◽  
Cortical Pyramidal Neurons ◽  
Apical Dendrites

Mechanisms underlying burst and regular spiking evoked by dendritic depolarization in layer 5 cortical pyramidal neurons. Apical dendrites of layer 5 pyramidal cells in a slice preparation of rat sensorimotor cortex were depolarized focally by long-lasting glutamate iontophoresis while recording intracellularly from their soma. In most cells the firing pattern evoked by the smallest dendritic depolarization that evoked spikes consisted of repetitive bursts of action potentials. During larger dendritic depolarizations initial burst firing was followed by regular spiking. As dendritic depolarization was increased further the duration (but not the firing rate) of the regular spiking increased, and the duration of burst firing decreased. Depolarization of the soma in most of the same cells evoked only regular spiking. When the dendrite was depolarized to a critical level below spike threshold, intrasomatic current pulses or excitatory postsynaptic potentials also triggered bursts instead of single spikes. The bursts were driven by a delayed depolarization (DD) that was triggered in an all-or-none manner along with the first Na+ spike of the burst. Somatic voltage-clamp experiments indicated that the action current underlying the DD was generated in the dendrite and was Ca2+ dependent. Thus the burst firing was caused by a Na+ spike-linked dendritic Ca2+spike, a mechanism that was available only when the dendrite was adequately depolarized. Larger dendritic depolarization that evoked late, constant-frequency regular spiking also evoked a long-lasting, Ca2+-dependent action potential (a “plateau”). The duration of the plateau but not its amplitude was increased by stronger dendritic depolarization. Burst-generating dendritic Ca2+spikes could not be elicited during this plateau. Thus plateau initiation was responsible for the termination of burst firing and the generation of the constant-frequency regular spiking. We conclude that somatic and dendritic depolarization can elicit quite different firing patterns in the same pyramidal neuron. The burst and regular spiking observed during dendritic depolarization are caused by two types of Ca2+-dependent dendritic action potentials. We discuss some functional implications of these observations.

Plasticity in an electrosensory system. I. General features of a dynamic sensory filter

1996 ◽  
Vol 76 (4) ◽  
pp. 2483-2496 ◽  
Author(s):  
J. Bastian
Keyword(s):  
Synaptic Plasticity ◽  
Pyramidal Cell ◽  
Electric Fish ◽  
Pyramidal Cells ◽  
Afferent Input ◽  
Firing Frequency ◽  
Negative Image ◽  
Local Stimulus ◽  
Adaptive Cancellation ◽  
Apical Dendrites

1. In this study we describe changes in neuronal responses within the primary electrosensory processing nucleus of a weakly electric fish that occur when the fish are exposed to repetitive patterns of electrosensory stimuli. Extracellular single-unit recordings show that pyramidal cells within the electrosensory lateral line lobe develop, over a time course of several minutes, an insensitivity to repetitive stimuli applied to a cell's receptive field (local stimulus). The pyramidal cell response cancellation only develops if the local stimulus is applied simultaneously with a diffuse pattern of electrosensory stimulation that affects the entire fish, or with proprioceptive stimuli. 2. The mechanism by which responses to repetitive afferent inputs are canceled relies on the central generation of "negative image inputs" that provide increased inhibitory input to a cell's apical dendrites at times when excitatory afferent input is increased. The negative image input becomes excitatory when afferent excitation is reduced or when input from inhibitory interneurons is predominant. The integration of a specific pattern of receptor afferent input with the complementary negative image input results in strong attenuation of pyramidal cell responses. The negative image inputs are plastic, so that a single pyramidal cell can learn to reject a variety of afferent input patterns. 3. These electric fish commonly experience repetitive electrosensory signals as a result of changes in posture. Because the electric organ is located in the trunk and tail, cyclical movements associated with exploratory behaviors result in amplitude modulations (AMs) of the electric field, and these AMs alter electroreceptor afferent firing frequency but not the firing frequency of second-order pyramidal cells. The adaptive cancellation mechanism described in this study can account for the insensitivity of pyramidal cells to reafferent electrosensory stimulation caused by tail movements and other postural changes. 4. The tail movements generate proprioceptive as well as electrosensory inputs, and either of these signals alone provides sufficient information for the generation of negative image inputs. The size of the negative image is larger, however, if both inputs are active. 5. The synaptic plasticity underlying the development of negative image inputs has a long-term component; under appropriate conditions changes in synaptic efficacy persist for > 30 min. 6. Normally functioning glutamatergic synapses are necessary for the expression of the synaptic plasticity associated with this cancellation mechanism. The development of negative image responses is blocked by micropressure ejection of the glutamate antagonist 6,7-dinitroquinoxaline-2,3-dione into the neighborhood of the pyramidal cell apical dendrites. 7. The adaptive cancellation of repetitive inputs is based on anti-Hebbian mechanisms; that is, correlated pre- and postsynaptic activity lead to a reduction in the excitatory input provided by the plastic synapses. As has been shown for several other systems, the cancellation mechanism reduces the cells responses to reafferent patterns of sensory input. In addition, the results of this study indicate that the mechanism may be more general, enabling the system to also cancel patterns of input resulting from exogenous stimuli.

Control of layer 5 pyramidal cell spiking by oscillatory inhibition in the distal apical dendrites: a computational modeling study

2013 ◽  
Vol 109 (11) ◽  
pp. 2739-2756 ◽  
Author(s):  
Xiumin Li ◽  
Kenji Morita ◽  
Hugh P. C. Robinson ◽  
Michael Small
Keyword(s):  
Pyramidal Cell ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Recurrent Inhibition ◽  
Aspartate Receptor ◽  
Coupled Cells ◽  
Single Spike ◽  
Cell Firing ◽  
The Impact ◽  
Apical Dendrites

The distal apical dendrites of layer 5 pyramidal neurons receive cortico-cortical and thalamocortical top-down and feedback inputs, as well as local recurrent inputs. A prominent source of recurrent inhibition in the neocortical circuit is somatostatin-positive Martinotti cells, which preferentially target distal apical dendrites of pyramidal cells. These electrically coupled cells can fire synchronously at various frequencies, including over a relatively slow range (5∼30 Hz), thereby imposing oscillatory inhibition on the pyramidal apical tuft dendrites. We examined how such distal oscillatory inhibition influences the firing of a biophysically detailed layer 5 pyramidal neuron model, which reproduced the spatiotemporal properties of sodium, calcium, and N-methyl-d-aspartate receptor spikes found experimentally. We found that oscillatory synchronization strongly influences the impact of distal inhibition on the pyramidal cell firing. Whereas asynchronous inhibition largely cancels out the facilitatory effects of distal excitatory inputs, inhibition oscillating synchronously at around 10∼20 Hz allows distal excitation to drive axosomatic firing, as if distal inhibition were absent. Underlying this is a switch from relatively infrequent burst firing to single spike firing at every period of the inhibitory oscillation. This phenomenon depends on hyperpolarization-activated cation current-dependent membrane potential resonance in the dendrite, but also, in a novel manner, on a cooperative amplification of this resonance by N-methyl-d-aspartate-receptor-driven dendritic action potentials. Our results point to a surprising dependence of the effect of recurrent inhibition by Martinotti cells on their oscillatory synchronization, which may control not only the local circuit activity, but also how it is transmitted to and decoded by downstream circuits.

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