scholarly journals Kv4 Accessory Protein DPPX (DPP6) is a Critical Regulator of Membrane Excitability in Hippocampal CA1 Pyramidal Neurons

2008 ◽  
Vol 100 (4) ◽  
pp. 1835-1847 ◽  
Author(s):  
Jinhyun Kim ◽  
Marcela S. Nadal ◽  
Ann M. Clemens ◽  
Matthew Baron ◽  
Sung-Cherl Jung ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Input Resistance ◽  
Physiological Effect ◽  
Membrane Excitability ◽  
Hippocampal Pyramidal Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
Kv4 Channels ◽  
Steady State Inactivation ◽  
Heterologous Expression Systems

A-type K+ currents have unique kinetic and voltage-dependent properties that allow them to finely tune synaptic integration, action potential (AP) shape and firing patterns. In hippocampal CA1 pyramidal neurons, Kv4 channels make up the majority of the somatodendritic A-type current. Studies in heterologous expression systems have shown that Kv4 channels interact with transmembrane dipeptidyl-peptidase-like proteins (DPPLs) to regulate the surface trafficking and biophysical properties of Kv4 channels. To investigate the influence of DPPLs in a native system, we conducted voltage-clamp experiments in patches from CA1 pyramidal neurons expressing short-interfering RNA (siRNA) targeting the DPPL variant known to be expressed in hippocampal pyramidal neurons, DPPX (siDPPX). In accordance with heterologous studies, we found that DPPX downregulation in neurons resulted in depolarizing shifts of the steady-state inactivation and activation curves, a shallower conductance-voltage slope, slowed inactivation, and a delayed recovery from inactivation for A-type currents. We carried out current-clamp experiments to determine the physiological effect of the A-type current modifications by DPPX. Neurons expressing siDPPX exhibited a surprisingly large reduction in subthreshold excitability as measured by a decrease in input resistance, delayed time to AP onset, and an increased AP threshold. Suprathreshold DPPX downregulation resulted in slower AP rise and weaker repolarization. Computer simulations supported our experimental results and demonstrated how DPPX remodeling of A-channel properties can result in opposing sub- and suprathreshold effects on excitability. The Kv4 auxiliary subunit DPPX thus acts to increase neuronal responsiveness and enhance signal precision by advancing AP initiation and accelerating both the rise and repolarization of APs.

scholarly journals Metformin Enhances Excitatory Synaptic Transmission onto Hippocampal CA1 Pyramidal Neurons

2020 ◽  
Vol 10 (10) ◽  
pp. 706
Author(s):  
Wen-Bing Chen ◽  
Jiang Chen ◽  
Zi-Yang Liu ◽  
Bin Luo ◽  
Tian Zhou ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Hippocampal Pyramidal Neurons ◽  
Beneficial Effects ◽  
Ca1 Pyramidal Neurons ◽  
Postsynaptic Currents ◽  
Hippocampal Ca1

Metformin (Met) is a first-line drug for type 2 diabetes mellitus (T2DM). Numerous studies have shown that Met exerts beneficial effects on a variety of neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). However, it is still largely unclear how Met acts on neurons. Here, by treating acute hippocampal slices with Met (1 μM and 10 μM) and recording synaptic transmission as well as neuronal excitability of CA1 pyramidal neurons, we found that Met treatments significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs), but not amplitude. Neither frequency nor amplitude of miniature inhibitory postsynaptic currents (mIPSCs) were changed with Met treatments. Analysis of paired-pulse ratios (PPR) demonstrates that enhanced presynaptic glutamate release from terminals innervating CA1 hippocampal pyramidal neurons, while excitability of CA1 pyramidal neurons was not altered. Our results suggest that Met preferentially increases glutamatergic rather than GABAergic transmission in hippocampal CA1, providing a new insight on how Met acts on neurons.

Ca2+ Channel Antagonist U-92032 Inhibits Both T-Type Ca2+ Channels and Na+ Channels in Hippocampal CA1 Pyramidal Neurons

1997 ◽  
Vol 77 (2) ◽  
pp. 1023-1028 ◽  
Author(s):  
Robert B. Avery ◽  
Daniel Johnston
Keyword(s):  
Pyramidal Neurons ◽  
Channel Blocker ◽  
Cell Voltage ◽  
Ionic Currents ◽  
Hippocampal Pyramidal Neurons ◽  
Voltage Gated ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
Old Rats ◽  
Ca2 Channels

Avery, Robert B. and Daniel Johnston. Ca2+ channel antagonist U-92032 inhibits both T-type Ca2+ channels and Na+ channels in hippocampal CA1 pyramidal neurons. J. Neurophysiol. 77: 1023–1028, 1997. The effects of 7-[[4-[bis(4-fluoropheny l ) - m e t h y l ] - 1 - p i p e r a z i n y l ] m e t h y l ] - 2 - [ ( 2 - h y d r o x y e t h y l ) a m i n o ]4 -( 1 - m e t h y l e t h y l ) - 2 , 4 , 6 - c y c l o h e p t a t r i e n - 1 - o n e  ( U - 9 2 0 3 2 ) ,  anewly described Ca2+ channel blocker, on voltage-gated ionic currents were measured. Whole cell voltage-clamp records were obtained from acutely isolated CA1 hippocampal pyramidal neurons from 7- to 14-day-old rats. Dimethyl sulfoxide, at either 0.01% or 0.1%, partially inhibited T-type Ca2+ currents (∼20% inhibition) but not high-voltage-activated (HVA) Ca2+ currents. Ethanol (0.2%) did not affect Ca2+ currents. U-92032 selectively inhibited T-type Ca2+ currents (median inhibiting concentration ∼ 500 nM). HVA Ca2+ currents were less sensitive, with ∼75% of the current resistant at 10 μM. Inhibition of Ca2+ currents was reversible. U-92032 inhibited Na+ currents at concentrations similar to those required for T-type currents (>33% block at 1 μM). Block of Na+ currents took several minutes to develop and was irreversible. Voltage-gated K+ currents were insensitive to U-92032 (1 or 10 μM). These results indicate that U-92032 inhibits both T-type Ca2+ channels and Na+ channels, constraining its utility in certain studies. Among Ca2+ channels, however, U-92032 should prove a useful tool for distinguishing physiological contributions of T-type channels.

Watermaze Learning Enhances Excitability of CA1 Pyramidal Neurons

2003 ◽  
Vol 90 (4) ◽  
pp. 2171-2179 ◽  
Author(s):  
M. Matthew Oh ◽  
Amy G. Kuo ◽  
Wendy W. Wu ◽  
Evgeny A. Sametsky ◽  
John F. Disterhoft
Keyword(s):  
Pyramidal Neurons ◽  
Dorsal Hippocampus ◽  
Eyeblink Conditioning ◽  
Hippocampal Pyramidal Neurons ◽  
Ca1 Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Platform Location ◽  
Dorsal Hippocampal ◽  
Hippocampal Ca1 ◽  
Trace Eyeblink Conditioning

The dorsal hippocampus is crucial for learning the hidden-platform location in the hippocampus-dependent, spatial watermaze task. We have previously demonstrated that the postburst afterhyperpolarization (AHP) of hippocampal pyramidal neurons is reduced after acquisition of the hippocampus-dependent, temporal trace eyeblink conditioning task. We report here that the AHP and one or more of its associated currents ( IAHP and/or s IAHP) are reduced in dorsal hippocampal CA1 pyramidal neurons from rats that learned the watermaze task as compared with neurons from control rats. This reduction was a learning-induced phenomenon as the AHP of CA1 neurons from rats that failed to learn the hidden-platform location was similar to that of neurons from control rats. We propose that reduction of the AHP in pyramidal neurons in regions crucial for learning is a cellular mechanism of learning that is conserved across species and tasks.

Endogenous PGE2 Regulates Membrane Excitability and Synaptic Transmission in Hippocampal CA1 Pyramidal Neurons

2005 ◽  
Vol 93 (2) ◽  
pp. 929-941 ◽  
Author(s):  
Chu Chen ◽  
Nicolas G. Bazan
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Inflammatory Responses ◽  
Perforant Path ◽  
Membrane Excitability ◽  
Dentate Granule Cell ◽  
Ca1 Pyramidal Neurons ◽  
Dendritic Membrane ◽  
Hippocampal Ca1 ◽  
Cox 2

The significance of cyclooxygenases (COXs), the rate-limiting enzymes that convert arachidonic acid (AA) to prostaglandins (PGs) in the brain, is unclear, although they have been implicated in inflammatory responses and in some neurological disorders such as epilepsy and Alzheimer's disease. Recent evidence that COX-2, which is expressed in postsynaptic dendritic spines, regulates PGE2 signaling in activity-dependent long-term synaptic plasticity at hippocampal perforant path-dentate granule cell synapses, suggests an important role of the COX-2–generated PGE2 in synaptic signaling. However, little is known of how endogenous PGE2 regulates neuronal signaling. Here we showed that endogenous PGE2 selectively regulates fundamental membrane and synaptic properties in the hippocampus. Somatic and dendritic membrane excitability was significantly reduced when endogenous PGE2 was eliminated with a selective COX-2 inhibitor in hippocampal CA1 pyramidal neurons in slices. Exogenous application of PGE2 produced significant increases in frequency of firing, excitatory postsynaptic potentials (EPSP) amplitude, and temporal summation in slices treated with the COX-2 inhibitor. The PGE2-induced increase in membrane excitability seemed to result from its inhibition of the potassium currents, which in turn, boosted dendritic Ca2+ influx during dendritic-depolarizing current injections. In addition, the PGE2-induced enhancement of EPSPs was blocked by eliminating both PKA and PKC activities. These findings indicate that endogenous PGE2 dynamically regulates membrane excitability, synaptic transmission, and plasticity and that the PGE2-induced synaptic modulation is mediated via cAMP-PKA and PKC pathways in rat hippocampal CA1 pyramidal neurons.

scholarly journals 3P221 The endocrine disrupter Bisphenol-A acutely induces morphologica changes in rat hippocampal CA1 pyramidal neurons

2004 ◽  
Vol 44 (supplement) ◽  
pp. S245
Author(s):  
N Tanabe ◽  
Y Komatsuzaki ◽  
T Tsurugizawa ◽  
K Mitsuhashi ◽  
Y Ooishi ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Pyramidal Neurons ◽  
Endocrine Disrupter ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1

scholarly journals Early Life Vitamin C Deficiency Does Not Alter Morphology of Hippocampal CA1 Pyramidal Neurons or Markers of Synaptic Plasticity in a Guinea Pig Model

Nutrients ◽  
2018 ◽  
Vol 10 (6) ◽  
pp. 749 ◽  
Author(s):  
Stine Hansen ◽  
Jane Jørgensen ◽  
Jens Nyengaard ◽  
Jens Lykkesfeldt ◽  
Pernille Tveden-Nyborg
Keyword(s):  
Synaptic Plasticity ◽  
Vitamin C ◽  
Guinea Pig ◽  
Early Life ◽  
Pyramidal Neurons ◽  
Pig Model ◽  
Vitamin C Deficiency ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
Guinea Pig Model
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