Extracellular alkaline shifts in rat hippocampal slice are mediated by NMDA and non-NMDA receptors

1. The pharmacology of synaptically evoked extracellular alkaline shifts was studied in the CA1 area of rat hippocampal slices. 2. Stimulus-evoked alkalinizations were unaffected by 2-amino-5-phosphonovalerate (APV) (20 microM). 3. 6-Cyano-7-nitro-nitroquinoxaline-2,3-dione (CNQX) (10 microM) inhibited the alkalinizations. In the continued presence of CNQX, an APV-sensitive, picrotoxin-insensitive, alkaline shift was elicited in low Mg2+ media. 4. Antidromic stimulation produced small alkaline shifts in comparison with orthodromic activation. 5. Our results demonstrate that in the hippocampal CA1 region, synaptically evoked alkalinizations can arise through both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors. These responses cannot be explained by cell firing per se.

Download Full-text

Noradrenergic Regulation of Synaptic Plasticity in the Hippocampal CA1 Region

Journal of Neurophysiology ◽

10.1152/jn.1997.77.6.3013 ◽

1997 ◽

Vol 77 (6) ◽

pp. 3013-3020 ◽

Cited By ~ 154

Author(s):

Hiroshi Katsuki ◽

Yukitoshi Izumi ◽

Charles F. Zorumski

Keyword(s):

Synaptic Plasticity ◽

Receptor Antagonist ◽

Hippocampal Slices ◽

Stimulus Frequency ◽

Long Term Potentiation ◽

Receptor Activation ◽

Ca1 Region ◽

Hippocampal Ca1 Region ◽

Hippocampal Ca1

Katsuki, Hiroshi, Yukitoshi Izumi, and Charles F. Zorumski. Noradrenergic regulation of synaptic plasticity in the hippocampal CA1 region. J. Neurophysiol. 77: 3013–3020, 1997. The effects of norepinephrine (NE) and related agents on long-lasting changes in synaptic efficacy induced by several patterns of afferent stimuli were investigated in the CA1 region of rat hippocampal slices. NE (10 μM) showed little effect on the induction of long-term potentiation (LTP) triggered by theta-burst-patterned stimulation, whereas it inhibited the induction of long-term depression (LTD) triggered by 900 pulses of 1-Hz stimulation. In nontreated slices, 900 pulses of stimuli induced LTD when applied at lower frequencies (1–3 Hz), and induced LTP when applied at a higher frequency (30 Hz). NE (10 μM) caused a shift of the frequency-response relationship in the direction preferring potentiation. The effect of NE was most prominent at a stimulus frequency of 10 Hz, which induced no changes in control slices but clearly induced LTP in the presence of NE. The facilitating effect of NE on the induction of LTP by 10-Hz stimulation was blocked by theβ-adrenergic receptor antagonist timolol (50 μM), but not by the α receptor antagonist phentolamine (50 μM), and was mimicked by the β-agonist isoproterenol (0.3 μM), but not by the α1 agonist phenylephrine (10 μM). The induction of LTD by 1-Hz stimulation was prevented by isoproterenol but not by phenylephrine, indicating that the activation of β-receptors is responsible for these effects of NE. NE (10 μM) also prevented the reversal of LTP (depotentiation) by 900 pulses of 1-Hz stimulation delivered 30 min after LTP induction. In contrast to effects on naive (nonpotentiated) synapses, the effect of NE on previously potentiated synapses was only partially mimicked by isoproterenol, but fully mimicked by coapplication of phenylephrine and isoproterenol. In addition, the effect of NE was attenuated either by phentolamine or by timolol, indicating that activation of both α1 and β-receptors is required. These results show that NE plays a modulatory role in the induction of hippocampal synaptic plasticity. Althoughβ-receptor activation is essential, α1 receptor activation is also necessary in determining effects on previously potentiated synapses.

Download Full-text

Long-Term Potentiation in the Hippocampal CA1 Region Does Not Require Insertion and Activation of GluR2-Lacking AMPA Receptors

Journal of Neurophysiology ◽

10.1152/jn.00473.2007 ◽

2007 ◽

Vol 98 (4) ◽

pp. 2488-2492 ◽

Cited By ~ 56

Author(s):

Erin E. Gray ◽

Ann E. Fink ◽

Joshua Sariñana ◽

Bryce Vissel ◽

Thomas J. O'Dell

Keyword(s):

Glutamate Receptor ◽

Ampa Receptors ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Ca1 Region ◽

Hippocampal Ca1 Region ◽

Term Potentiation ◽

Hippocampal Ca1 ◽

Old Mice

Activity-dependent insertion of AMPA-type glutamate receptors is thought to underlie long-term potentiation (LTP) at Schaffer collateral fiber synapses on pyramidal cells in the hippocampal CA1 region. Although it is widely accepted that the AMPA receptors at these synapses contain glutamate receptor type 2 (GluR2) subunits, recent findings suggest that LTP in hippocampal slices obtained from 2- to 3-wk-old rodents is dependent on the transient postsynaptic insertion and activation of Ca2+-permeable, GluR2-lacking AMPA receptors. Here we examined whether LTP in slices prepared from adult animals exhibits similar properties. In contrast to previously reported findings, pausing synaptic stimulation for as long as 30 min post LTP induction had no effect on LTP maintenance in slices from 2- to 3-mo-old mice. LTP was also not disrupted by postinduction application of a selective blocker of GluR2-lacking AMPA receptors or the broad-spectrum glutamate receptor antagonist kynurenate. Although these results suggest that the role of GluR2-lacking AMPA receptors in LTP might be regulated during postnatal development, LTP in slices obtained from 15- to 21-day-old mice also did not require postinduction synaptic stimulation or activation of GluR2-lacking AMPA receptors. Thus the insertion and activation of GluR2-lacking AMPA receptors do not appear to be fundamental processes involved in LTP at excitatory synapses in the hippocampal CA1 region.

Download Full-text

Effects of Chronic Stress and Phenytoin on the Long-term Potentiation (LTP) in Rat Hippocampal CA1 Region

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/36.5.375 ◽

2004 ◽

Vol 36 (5) ◽

pp. 375-378 ◽

Cited By ~ 13

Author(s):

Hui Zheng ◽

Quan Yang ◽

Chong-Tao Xu

Keyword(s):

Chronic Stress ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Saline Group ◽

Control Group ◽

Ca1 Region ◽

Hippocampal Ca1 Region ◽

Term Potentiation ◽

Hippocampal Ca1 ◽

Hippocampal Ca1 Field

Abstract To investigate the changes of LTP in hippocampal CA1 region induced by chronic stress and the effect of phenytoin on them, thirty-two adult male Sprague-Dawley rats were randomly divided equally into four groups: control group, control-phenytoin group, stress-saline group and stress-phenytoin group. Isolated hippocampal slices of rats were used to observe the changes of long-term potentiation (LTP) in hippocampal CA1 field using electrophysiological technique. Amplitude of population spike (PS) and field excitatory postsynaptic potentials (fEPSPs) slope were used to indicate the changes of LTP. High-frequency stimulation (HFS) was applied to Schaffer collaterals of hippocampal CA3 field, and the changes of PS amplitude and fEPSPs slope in CA1 field were observed. The results showed that the LTP induction rate, the increases of PS amplitude and fEPSPs slope after HFS in control and stress-phenytoin groups were significantly greater than those in stress-saline group (P<0.05). There were no significant differences between control group and stressphenytoin group or between control and control-phenytoin groups in these indexes (P<0.05). It is suggested that chronic stress can damage the development of LTP in hippocampal CA1 field, while phenytoin can protect the LTP of stressed hippocampal slices in normal state.

Download Full-text