scholarly journals Long-Term Inactivation of Sodium Channels as a Mechanism of Adaptation in CA1 Pyramidal Neurons

2021 ◽  
Author(s):  
Carol Upchurch ◽  
Crescent L. Combe ◽  
Christopher Knowlton ◽  
Valery G. Rousseau ◽  
Sonia Gasparini ◽  
...  
Keyword(s):  
Spatial Dependence ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Firing Frequency ◽  
Place Field ◽  
Spike Amplitude ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Pyramidal Neurons

The hippocampus is involved in memory and spatial navigation. Many CA1 pyramidal cells function as place cells, increasing their firing rate when a specific place field is traversed. The dependence of CA1 place cell firing on position within the place field is asymmetric. We investigated the source of this asymmetry by injecting triangular depolarizing current ramps to approximate the spatially-tuned, temporally-diffuse depolarizing synaptic input received by these neurons while traversing a place field. Ramps were applied to rat CA1 pyramidal neurons in vitro (slice electrophysiology) and in silico (multi-compartmental NEURON model). Under control conditions, CA1 neurons fired more action potentials at higher frequencies on the up-ramp versus the down-ramp. This effect was more pronounced for dendritic compared to somatic ramps. We incorporated a five-state Markov scheme for NaV1.6 channels into our model and calibrated the spatial dependence of long-term inactivation according to the literature; this spatial dependence was sufficient to explain the difference in dendritic versus somatic ramps. Long-term inactivation reduced the firing frequency by decreasing open-state occupancy, and reduced spike amplitude during trains by decreasing occupancy in closed states, which comprise the available pool. PKC activators like phorbol ester phorbol-dibutyrate (PDBu) are known to reduce NaV long-term inactivation. PDBu application removed spike amplitude attenuation during spike trains in vitro, more visibly in dendrites, consistent with decreased NaV long-term inactivation. Moreover, PDBu greatly reduced adaptation, consistent with our hypothesized mechanism. Our synergistic experimental/computational approach shows that long-term inactivation of NaV1.6 is the primary mechanism of adaptation in CA1 pyramidal cells.

scholarly journals Disinhibitory and neuromodulatory regulation of hippocampal synaptic plasticity

2020 ◽  
Author(s):  
Inês Guerreiro ◽  
Zhenglin Gu ◽  
Jerrel L. Yakel ◽  
Boris S. Gutkin
Keyword(s):  
Synaptic Plasticity ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
General Mechanism ◽  
Excitatory Synapses ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Synaptic Plasticity ◽  
Local Circuitry ◽  
Feedforward Inhibition

AbstractHippocampal synaptic plasticity, particularly in the Schaffer collateral (SC) to CA1 pyramidal excitatory transmission, is considered as the cellular mechanism underlying learning. The CA1 pyramidal neurons are embedded in an intricate local circuitry that contains a variety of interneurons. The roles these interneurons play in the regulation of the excitatory synaptic plasticity remains largely understudied. Our recent experiments showed that repeated cholinergic activation of α7 nACh receptors expressed in oriens-lacunosum-moleculare (OLMα2) interneurons could induce LTP in SC-CA1 synapses, likely through disinhibition by inhibiting stratum radiatum (s.r.) interneurons that provide feedforward inhibition onto CA1 pyramidal neurons, revealing a potential mechanism for local interneurons to regulate SC-CA1 synaptic plasticity. Here, we pair in vitro studies with biophysically-based modeling to uncover the mechanisms through which cholinergic-activated GABAergic interneurons can disinhibit CA1 pyramidal cells, and how repeated disinhibition modulates hippocampal plasticity at the excitatory synapses. We found that α7 nAChR activation increases OLM activity. OLM neurons, in turn inhibit the fast-spiking interneurons that provide feedforward inhibition onto CA1 pyramidal neurons. This disinhibition, paired with tightly timed SC stimulation, can induce potentiation at the excitatory synapses of CA1 pyramidal neurons. Our work further describes the pairing of disinhibition with SC stimulation as a general mechanism for the induction of hippocampal synaptic plasticity.Disinhibition of the excitatory synapses, paired with SC stimulation, leads to increased NMDAR activation and intracellular calcium concentration sufficient to upregulate AMPAR permeability and potentiate the synapse. Repeated paired disinhibition of the excitatory synapse leads to larger and longer lasting increases of the AMPAR permeability. Our study thus provides a novel mechanism for inhibitory interneurons to directly modify glutamatergic synaptic plasticity. In particular, we show how cholinergic action on OLM interneurons can down-regulate the GABAergic signaling onto CA1 pyramidal cells, and how this shapes local plasticity rules. We identify paired disinhibition with SC stimulation as a general mechanism for the induction of hippocampal synaptic plasticity.

scholarly journals Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output

2019 ◽  
Author(s):  
Matt Udakis ◽  
Victor Pedrosa ◽  
Sophie E.L. Chamberlain ◽  
Claudia Clopath ◽  
Jack R Mellor
Keyword(s):  
Pyramidal Neurons ◽  
Physiological Activity ◽  
Activity Patterns ◽  
Pyramidal Cells ◽  
Network Activity ◽  
Inhibitory Synapses ◽  
Ca1 Pyramidal Cells ◽  
Hippocampal Cell ◽  
Hippocampal Network

SummaryThe formation and maintenance of spatial representations within hippocampal cell assemblies is strongly dictated by patterns of inhibition from diverse interneuron populations. Although it is known that inhibitory synaptic strength is malleable, induction of long-term plasticity at distinct inhibitory synapses and its regulation of hippocampal network activity is not well understood. Here, we show that inhibitory synapses from parvalbumin and somatostatin expressing interneurons undergo long-term depression and potentiation respectively (PV-iLTD and SST-iLTP) during physiological activity patterns. Both forms of plasticity rely on T-type calcium channel activation to confer synapse specificity but otherwise employ distinct mechanisms. Since parvalbumin and somatostatin interneurons preferentially target perisomatic and distal dendritic regions respectively of CA1 pyramidal cells, PV-iLTD and SST-iLTP coordinate a reprioritisation of excitatory inputs from entorhinal cortex and CA3. Furthermore, circuit-level modelling reveals that PV-iLTD and SST-iLTP cooperate to stabilise place cells while facilitating representation of multiple unique environments within the hippocampal network.

Distribution of Slow AHP Channels on Hippocampal CA1 Pyramidal Neurons

2000 ◽  
Vol 83 (3) ◽  
pp. 1756-1759 ◽  
Author(s):  
John M. Bekkers
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Apical Dendrite ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Pyramidal Neurons ◽  
Basal Dendrites ◽  
Hippocampal Ca1 ◽  
Cell Current ◽  
Whole Cell Current

This work was designed to localize the Ca2+-activated K+ channels underlying the slow afterhyperpolarization (sAHP) in hippocampal CA1 pyramidal cells. Cell-attached patches on the proximal 100 μm of the apical dendrite contained K+ channels, but not sAHP channels, activated by backpropagating action potentials. Amputation of the apical dendrite ∼30 μm from the soma, while simultaneously recording the sAHP whole cell current at the soma, depressed the sAHP amplitude by only ∼30% compared with control. Somatic cell-attached and nucleated patches did not contain sAHP current. Amputation of the axon ≥20 μm from the soma had little effect on the amplitude of the sAHP recorded in cortical pyramidal cells. By this process of elimination, it is suggested that sAHP channels may be concentrated in the basal dendrites of CA1 pyramids.

Acetylcholine Sensitivity of Hippocampal Formation Neurons

1974 ◽  
Vol 52 (5) ◽  
pp. 966-971 ◽  
Author(s):  
B. H. Bland ◽  
G. K. Kostopoulos ◽  
J. W. Phillis
Keyword(s):  
Pyramidal Neurons ◽  
Granule Cells ◽  
Hippocampal Formation ◽  
Pyramidal Cells ◽  
Dentate Granule Cells ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Pyramidal Neurons ◽  
Acetylcholine Sensitivity ◽  
Two Populations ◽  
Number Of Cells

Microiontophoretic application of acetylcholine to neurons in the CA1 pyramidal and dentate granule layers of the rabbit hippocampus revealed differences both in the number of cells excited and the nature of the excitation in the two populations of neurons. A smaller percentage (35.7%) of CA1 pyramidal neurons were found to be excited by acetylcholine, compared with the percentage (92.3%) of dentate granule cells excited. Excitation of CA1 pyramidal cells was slow in onset and antagonized by atropine. Excitation of dentate granule cells was rapid in onset and atropine did not specifically antagonize the action of acetylcholine on these cells.

scholarly journals Synaptic GABAA Activation Inhibits AMPA-Kainate Receptor–Mediated Bursting in the Newborn (P0–P2) Rat Hippocampus

2000 ◽  
Vol 83 (1) ◽  
pp. 359-366 ◽  
Author(s):  
Karri Lamsa ◽  
J. Matias Palva ◽  
Eva Ruusuvuori ◽  
Kai Kaila ◽  
Tomi Taira
Keyword(s):  
Pyramidal Neurons ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Neuronal Population ◽  
Excitatory Input ◽  
Calcium Oscillations ◽  
Rat Hippocampus ◽  
Network Activity ◽  
Ca1 Pyramidal Cells

The mechanisms of synaptic transmission in the rat hippocampus at birth are assumed to be fundamentally different from those found in the adult. It has been reported that in the CA3-CA1 pyramidal cells a conversion of “silent” glutamatergic synapses to conductive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) synapses starts gradually after P2. Further, GABA via its depolarizing action seems to give rise to grossly synchronous yet slow calcium oscillations. Therefore, GABA is generally thought to have a purely excitatory rather than an inhibitory role during the first postnatal week. In the present study field potential recordings and gramicidin perforated and whole cell clamp techniques as well as K+-selective microelectrodes were used to examine the relative contributions of AMPA and GABAA receptors to network activity of CA3-CA1 pyramidal cells in the newborn rat hippocampus. As early as postnatal day( P 0–P2), highly coherent spontaneous firing of CA3 pyramidal cells was seen in vitro. Negative-going extracellular spikes confined to periodic bursts (interval 16 ± 3 s) consisting of 2.9 ± 0.1 spikes were observed in stratum pyramidale. The spikes were accompanied by AMPA-R–mediated postsynaptic currents (PSCs) in simultaneously recorded pyramidal neurons (7.6 ± 3.0 unitary currents per burst). In CA1 pyramidal cells synchronous discharging of CA3 circuitry produced a barrage of AMPA currents at >20 Hz frequencies, thus demonstrating a transfer of the fast CA3 network activity to CA1 area. Despite its depolarizing action, GABAA-R–mediated transmission appeared to exert inhibition in the CA3 pyramidal cell population. The GABAA-R antagonist bicuculline hypersynchronized the output of glutamatergic CA3 circuitry and increased the network-driven excitatory input to the pyramidal neurons, whereas the GABAA-R agonist muscimol (100 nM) did the opposite. However, the occurrence of unitary GABAA-R currents was increased after muscimol application from 0.66 ± 0.16 s−1 to 1.43 ± 0.29 s−1. It was concluded that AMPA synapses are critical in the generation of spontaneous high-frequency bursts in CA3 as well as in CA3-CA1 transmission as early as P0–P2 in rat hippocampus. Concurrently, although GABAA-R–mediated depolarization may excite hippocampal interneurons, in CA3 pyramidal neurons it can restrain excitatory inputs and limit the size of the activated neuronal population.

scholarly journals SK (KCa2) Channels Do Not Control Somatic Excitability in CA1 Pyramidal Neurons But Can Be Activated by Dendritic Excitatory Synapses and Regulate Their Impact

2008 ◽  
Vol 100 (5) ◽  
pp. 2589-2604 ◽  
Author(s):  
Ning Gu ◽  
Hua Hu ◽  
Koen Vervaeke ◽  
Johan F. Storm
Keyword(s):  
Pyramidal Neurons ◽  
Calcium Influx ◽  
Pyramidal Cells ◽  
Spike Trains ◽  
Mammalian Brain ◽  
Sk Channels ◽  
Cell Type ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Pyramidal Neurons ◽  
Sk Channel

Calcium-activated K+ channels of the KCa2 type (SK channels) are prominently expressed in the mammalian brain, including hippocampus. These channels are thought to underlie neuronal excitability control and have been implicated in plasticity, memory, and neural disease. Contrary to previous reports, we found that somatic spike-evoked medium afterhyperpolarizations (mAHPs) and corresponding excitability control were not caused by SK channels but mainly by Kv7/KCNQ/M channels in CA1 hippocampal pyramidal neurons. Thus apparently, these SK channels are hardly activated by somatic Na+ spikes. To further test this conclusion, we used sharp electrode, whole cell, and perforated-patch recordings from rat CA1 pyramidal neurons. We found that SK channel blockers consistently failed to suppress mAHPs under a range of experimental conditions: mAHPs following single spikes or spike trains, at −60 or −80 mV, at 20–30°C, in low or elevated extracellular [K+], or spike trains triggered by synaptic stimulation after blocking N-methyl-d-aspartic acid receptors (NMDARs). Nevertheless, we found that SK channels in these cells were readily activated by artificially enhanced Ca2+ spikes, and an SK channel opener (1-ethyl-2-benzimidazolinone) enhanced somatic AHPs following Na+ spikes, thus reducing excitability. In contrast to CA1 pyramidal cells, bursting pyramidal cells in the subiculum showed a Na+ spike-evoked mAHP that was reduced by apamin, indicating cell-type-dependent differences in mAHP mechanisms. Testing for other SK channel functions in CA1, we found that field excitatory postsynaptic potentials mediated by NMDARs were enhanced by apamin, supporting the idea that dendritic SK channels are activated by NMDAR-dependent calcium influx. We conclude that SK channels in rat CA1 pyramidal cells can be activated by NMDAR-mediated synaptic input and cause feedback regulation of synaptic efficacy but are normally not appreciably activated by somatic Na+ spikes in this cell type.

scholarly journals Selective Induction of LTP and LTD by Postsynaptic [Ca2+]i Elevation

1999 ◽  
Vol 81 (2) ◽  
pp. 781-787 ◽  
Author(s):  
Shao-Nian Yang ◽  
Yun-Gui Tang ◽  
Robert S. Zucker
Keyword(s):  
Calcium Concentration ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Biological Information ◽  
Synaptic Modulation ◽  
Ca1 Pyramidal Cells ◽  
Caged Calcium ◽  
Term Potentiation ◽  
Calcium Compound

Selective Induction of LTP and LTD by Postsynaptic [Ca2+]i Elevation. Long-term potentiation (LTP) and long-term depression (LTD), two prominent forms of synaptic plasticity at glutamatergic afferents to CA1 hippocampal pyramidal cells, are both triggered by the elevation of postsynaptic intracellular calcium concentration ([Ca2+]i). To understand how one signaling molecule can be responsible for triggering two opposing forms of synaptic modulation, different postsynaptic [Ca2+]i elevation patterns were generated by a new caged calcium compound nitrophenyl-ethylene glycol-bis(β-aminoethyl ether)- N, N, N′, N′-tetraacetic acid in CA1 pyramidal cells. We found that specific patterns of [Ca2+]i elevation selectively activate LTP or LTD. In particular, only LTP was triggered by a brief increase of [Ca2+]i with relatively high magnitude, which mimics the [Ca2+]i rise during electrical stimulation typically used to induce LTP. In contrast, a prolonged modest rise of [Ca2+]i reliably induced LTD. An important implication of the results is that both the amplitude and the duration of an intracellular chemical signal can carry significant biological information.

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.

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