scholarly journals IK1 channels do not contribute to the slow afterhyperpolarization in pyramidal neurons

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Kang Wang ◽  
Pedro Mateos-Aparicio ◽  
Christoph Hönigsperger ◽  
Vijeta Raghuram ◽  
Wendy W Wu ◽  
...  
Keyword(s):  
Action Potentials ◽  
Basolateral Amygdala ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
K Channel ◽  
Memory Decline ◽  
Ca1 Pyramidal Neurons ◽  
Molecular Identity ◽  
Age Related ◽  
Hippocampal Area

In pyramidal neurons such as hippocampal area CA1 and basolateral amygdala, a slow afterhyperpolarization (sAHP) follows a burst of action potentials, which is a powerful regulator of neuronal excitability. The sAHP amplitude increases with aging and may underlie age related memory decline. The sAHP is due to a Ca2+-dependent, voltage-independent K+ conductance, the molecular identity of which has remained elusive until a recent report suggested the Ca2+-activated K+ channel, IK1 (KCNN4) as the sAHP channel in CA1 pyramidal neurons. The signature pharmacology of IK1, blockade by TRAM-34, was reported for the sAHP and underlying current. We have examined the sAHP and find no evidence that TRAM-34 affects either the current underling the sAHP or excitability of CA1 or basolateral amygdala pyramidal neurons. In addition, CA1 pyramidal neurons from IK1 null mice exhibit a characteristic sAHP current. Our results indicate that IK1 channels do not mediate the sAHP in pyramidal neurons.

scholarly journals Redox Sensitive Calcium Stores Underlie Enhanced After Hyperpolarization of Aged Neurons: Role for Ryanodine Receptor Mediated Calcium Signaling

2010 ◽  
Vol 104 (5) ◽  
pp. 2586-2593 ◽  
Author(s):  
Karthik Bodhinathan ◽  
Ashok Kumar ◽  
Thomas C. Foster
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Slow Component ◽  
Ryanodine Receptors ◽  
Calcium Stores ◽  
Memory Decline ◽  
Ca1 Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Age Related ◽  
Intracellular Ca

A decrease in the excitability of CA1 pyramidal neurons contributes to the age related decrease in hippocampal function and memory decline. Decreased neuronal excitability in aged neurons can be observed as an increase in the Ca2+- activated K+- mediated post burst afterhyperpolarization (AHP). In this study, we demonstrate that the slow component of AHP (sAHP) in aged CA1 neurons (aged-sAHP) is decreased ∼50% by application of the reducing agent dithiothreitol (DTT). The DTT-mediated decrease in the sAHP was age specific, such that it was observed in CA1 pyramidal neurons of aged (20–25 mo), but not young (6–9 mo) F344 rats. The effect of DTT on the aged-sAHP was blocked following depletion of intracellular Ca2+ stores (ICS) by thapsigargin or blockade of ryanodine receptors (RyRs) by ryanodine, suggesting that the age-related increase in the sAHP was due to release of Ca2+ from ICS through redox sensitive RyRs. The DTT-mediated decrease in the aged-sAHP was not blocked by inhibition of L-type voltage gated Ca2+ channels (L-type VGCC), inhibition of Ser/Thr kinases, or inhibition of the large conductance BK potassium channels. The results add support to the idea that a shift in the intracellular redox state contributes to Ca2+ dysregulation during aging.

Dichotomy of Action-Potential Backpropagation in CA1 Pyramidal Neuron Dendrites

2001 ◽  
Vol 86 (6) ◽  
pp. 2998-3010 ◽  
Author(s):  
Nace L. Golding ◽  
William L. Kath ◽  
Nelson Spruston
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Synaptic Activity ◽  
Resting Potential ◽  
Model Parameters ◽  
Voltage Sensitivity ◽  
Whole Cell ◽  
Ca1 Pyramidal Neurons ◽  
Whole Cell Recordings

In hippocampal CA1 pyramidal neurons, action potentials are typically initiated in the axon and backpropagate into the dendrites, shaping the integration of synaptic activity and influencing the induction of synaptic plasticity. Despite previous reports describing action-potential propagation in the proximal apical dendrites, the extent to which action potentials invade the distal dendrites of CA1 pyramidal neurons remains controversial. Using paired somatic and dendritic whole cell recordings, we find that in the dendrites proximal to 280 μm from the soma, single backpropagating action potentials exhibit <50% attenuation from their amplitude in the soma. However, in dendritic recordings distal to 300 μm from the soma, action potentials in most cells backpropagated either strongly (26–42% attenuation; n = 9/20) or weakly (71–87% attenuation; n = 10/20) with only one cell exhibiting an intermediate value (45% attenuation). In experiments combining dual somatic and dendritic whole cell recordings with calcium imaging, the amount of calcium influx triggered by backpropagating action potentials was correlated with the extent of action-potential invasion of the distal dendrites. Quantitative morphometric analyses revealed that the dichotomy in action-potential backpropagation occurred in the presence of only subtle differences in either the diameter of the primary apical dendrite or branching pattern. In addition, action-potential backpropagation was not dependent on a number of electrophysiological parameters (input resistance, resting potential, voltage sensitivity of dendritic spike amplitude). There was, however, a striking correlation of the shape of the action potential at the soma with its amplitude in the dendrite; larger, faster-rising, and narrower somatic action potentials exhibited more attenuation in the distal dendrites (300–410 μm from the soma). Simple compartmental models of CA1 pyramidal neurons revealed that a dichotomy in action-potential backpropagation could be generated in response to subtle manipulations of the distribution of either sodium or potassium channels in the dendrites. Backpropagation efficacy could also be influenced by local alterations in dendritic side branches, but these effects were highly sensitive to model parameters. Based on these findings, we hypothesize that the observed dichotomy in dendritic action-potential amplitude is conferred primarily by differences in the distribution, density, or modulatory state of voltage-gated channels along the somatodendritic axis.

scholarly journals Lateral entorhinal cortex inputs modulate hippocampal dendritic excitability by recruiting a local disinhibitory microcircuit

2022 ◽  
Author(s):  
Olesia M Bilash ◽  
Spyridon Chavlis ◽  
Panayiota Poirazi ◽  
Jayeeta Basu
Keyword(s):  
Entorhinal Cortex ◽  
Pyramidal Neurons ◽  
Inhibitory Neuron ◽  
Inhibitory Neurons ◽  
Environmental Cues ◽  
Memory Processing ◽  
Ca1 Pyramidal Neurons ◽  
Dendritic Spikes ◽  
Hippocampal Area ◽  
Insight Into

The lateral entorhinal cortex (LEC) provides information about multi-sensory environmental cues to the hippocampus through direct inputs to the distal dendrites of CA1 pyramidal neurons. A growing body of work suggests that LEC neurons perform important functions for episodic memory processing, coding for contextually-salient elements of an environment or the experience within it. However, we know little about the functional circuit interactions between LEC and the hippocampus. In this study, we combine functional circuit mapping and computational modeling to examine how long-range glutamatergic LEC projections modulate compartment-specific excitation-inhibition dynamics in hippocampal area CA1. We demonstrate that glutamatergic LEC inputs can drive local dendritic spikes in CA1 pyramidal neurons, aided by the recruitment of a disinhibitory vasoactive intestinal peptide (VIP)-expressing inhibitory neuron microcircuit. Our circuit mapping further reveals that, in parallel, LEC also recruits cholecystokinin (CCK)-expressing inhibitory neurons, which our model predicts act as a strong suppressor of dendritic spikes. These results provide new insight into a cortically-driven GABAergic microcircuit mechanism that gates non-linear dendritic computations, which may support compartment-specific coding of multi-sensory contextual features within the hippocampus.

Resting and Active Properties of Pyramidal Neurons in Subiculum and CA1 of Rat Hippocampus

2000 ◽  
Vol 84 (5) ◽  
pp. 2398-2408 ◽  
Author(s):  
Nathan P. Staff ◽  
Hae-Yoon Jung ◽  
Tara Thiagarajan ◽  
Michael Yao ◽  
Nelson Spruston
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Current Injection ◽  
Synaptic Integration ◽  
Membrane Properties ◽  
Neuronal Membrane ◽  
Similar Action ◽  
Ca1 Neurons ◽  
Ca1 Pyramidal Neurons

Action potentials are the end product of synaptic integration, a process influenced by resting and active neuronal membrane properties. Diversity in these properties contributes to specialized mechanisms of synaptic integration and action potential firing, which are likely to be of functional significance within neural circuits. In the hippocampus, the majority of subicular pyramidal neurons fire high-frequency bursts of action potentials, whereas CA1 pyramidal neurons exhibit regular spiking behavior when subjected to direct somatic current injection. Using patch-clamp recordings from morphologically identified neurons in hippocampal slices, we analyzed and compared the resting and active membrane properties of pyramidal neurons in the subiculum and CA1 regions of the hippocampus. In response to direct somatic current injection, three subicular firing types were identified (regular spiking, weak bursting, and strong bursting), while all CA1 neurons were regular spiking. Within subiculum strong bursting neurons were found preferentially further away from the CA1 subregion. Input resistance ( R N), membrane time constant (τm), and depolarizing “sag” in response to hyperpolarizing current pulses were similar in all subicular neurons, while R N and τm were significantly larger in CA1 neurons. The first spike of all subicular neurons exhibited similar action potential properties; CA1 action potentials exhibited faster rising rates, greater amplitudes, and wider half-widths than subicular action potentials. Therefore both the resting and active properties of CA1 pyramidal neurons are distinct from those of subicular neurons, which form a related class of neurons, differing in their propensity to burst. We also found that both regular spiking subicular and CA1 neurons could be transformed into a burst firing mode by application of a low concentration of 4-aminopyridine, suggesting that in both hippocampal subfields, firing properties are regulated by a slowly inactivating, D-type potassium current. The ability of all subicular pyramidal neurons to burst strengthens the notion that they form a single neuronal class, sharing a burst generating mechanism that is stronger in some cells than others.

scholarly journals Metrifonate Increases Neuronal Excitability in CA1 Pyramidal Neurons from Both Young and Aging Rabbit Hippocampus

1999 ◽  
Vol 19 (5) ◽  
pp. 1814-1823 ◽  
Author(s):  
M. Matthew Oh ◽  
John M. Power ◽  
Lucien T. Thompson ◽  
Pamela L. Moriearty ◽  
John F. Disterhoft
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Rabbit Hippocampus

scholarly journals Decreased IH in Hippocampal Area CA1 Pyramidal Neurons after Perinatal Seizure-inducing Hypoxia

Epilepsia ◽  
2006 ◽  
Vol 47 (6) ◽  
pp. 1023-1028 ◽  
Author(s):  
Kun Zhang ◽  
Bi-wen Peng ◽  
Russell M. Sanchez
Keyword(s):  
Pyramidal Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Area Ca1 ◽  
Hippocampal Area

scholarly journals Of mice and intrinsic excitability: genetic background affects the size of the postburst afterhyperpolarization in CA1 pyramidal neurons

2011 ◽  
Vol 106 (3) ◽  
pp. 1570-1580 ◽  
Author(s):  
Shannon J. Moore ◽  
Benjamin T. Throesch ◽  
Geoffrey G. Murphy
Keyword(s):  
Genetic Background ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Critical Role ◽  
Genetically Engineered ◽  
Gradual Transition ◽  
Cellular Mechanisms ◽  
Ca1 Pyramidal Neurons ◽  
Genetically Engineered Mice ◽  
Cell Current

As the use of genetically engineered mice has become increasingly prevalent in neurobiological research, evidence has steadily accumulated that substantial differences exist between strains. Although a number of studies have reported effects of genetic background on behavior, few have focused on differences in neurophysiology. The postburst afterhyperpolarization (AHP) is an important determinant of intrinsic neuronal excitability and has been suggested to play a critical role in the cellular mechanisms underlying learning and memory. Using whole cell current-clamp recordings of CA1 pyramidal neurons, we examined the magnitude of different phases of the AHP (peak, medium, and slow) in two commonly used genetic backgrounds, C57BL/6 (B6) and 129SvEv (129), as well as in an F2 hybrid B6:129 background (F2). We found that neurons from B6 and F2 animals exhibited a significantly larger AHP compared with 129 animals and that this difference was consistent across all phases. Furthermore, our recordings revealed a marked dichotomy in the shape of the AHP waveform, which was independent of genetic background. Approximately 60% of cells exhibited an AHP with a sharp transition between the peak AHP and medium AHP, whereas the remaining 40% exhibited a more gradual transition. Our data add to the growing body of work suggesting that genetic background can affect neuronal function as well as behavior. In addition, these results highlight the innate heterogeneity of CA1 pyramidal neurons, even within a single genetic background. These differences should be taken into consideration during the analysis and comparison of experimental results.

Metrifonate Decreases sI AHP in CA1 Pyramidal Neurons In Vitro

2001 ◽  
Vol 85 (1) ◽  
pp. 319-322 ◽  
Author(s):  
John M. Power ◽  
M. Mathew Oh ◽  
John F. Disterhoft
Keyword(s):  
Pyramidal Neurons ◽  
Slow Component ◽  
Cell Voltage ◽  
Current Clamp ◽  
Hippocampal Pyramidal Neurons ◽  
Tail Current ◽  
Electrode Current ◽  
Ca1 Pyramidal Neurons ◽  
Age Related

Metrifonate, a cholinesterase inhibitor, has been shown to enhance learning in aging rabbits and rats, and to alleviate the cognitive deficits observed in Alzheimer's disease patients. We have previously determined that bath application of metrifonate reduces the spike frequency adaptation and postburst afterhyperpolarization (AHP) in rabbit CA1 pyramidal neurons in vitro using sharp electrode current-clamp recording. The postburst AHP and accommodation observed in current clamp are the result of four slow outward potassium currents (s I AHP, I AHP, I M, and I C) and the hyperpolarization activated mixed cation current, I h. We recorded from visually identified CA1 hippocampal pyramidal neurons in vitro using whole cell voltage-clamp technique to better isolate and characterize which component currents of the AHP are affected by metrifonate. We observed an age-related enhancement of the slow component of the AHP tail current (s I AHP), but not of the fast decaying component of the AHP tail current ( I AHP, I M, and I C). Bath perfusion of metrifonate reduced s I AHP at concentrations that cause a reduction of the AHP and accommodation in current-clamp recordings, with no apparent reduction of I AHP, I M, and I C. The functional consequences of metrifonate administration are apparently mediated solely through modulation of the s I AHP.

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