Cannabinoids selectively decrease paired-pulse facilitation of perforant path synaptic potentials in the dentate gyrus in vitro

1. Activation of kappa 1-opioid receptors inhibits excitatory transmission in the hippocampal dentate gyrus of the guinea pig. The present studies used both anatomic and physiological approaches to distinguish between a pre- and postsynaptic localization of these receptors. 2. The entorhinal cortex was lesioned unilaterally to cause degeneration of perforant path afferents to the dentate molecular layer, and kappa 1-opioid binding sites were measured by labeling with the selective agonist, [3H]-U69593. Binding density was reduced significantly in the dentate gyrus molecular layer ipsilateral to the lesion compared with the contralateral molecular layer and with sham-lesioned controls. 3. Paired-pulse facilitation is a neurophysiologic paradigm that has been used to differentiate pre- and postsynaptic sites of action for agents that inhibit excitatory neurotransmission. U69593 reduced the amplitude of single population spikes and increased the degree of paired pulse facilitation. The potentiation of paired-pulse facilitation was maintained when the stimulation intensity was increased to compensate for the inhibition of excitatory transmission. These effects of kappa 1-receptor activation were similar to those seen after presynaptic inhibition of excitatory neurotransmitter release and support the hypothesis that U69593 presynaptically inhibits excitatory amino acid release in the dentate gyrus. 4. Local application of glutamate by pressure ejection in the dentate molecular layer evoked field excitatory postsynaptic potentials that mimicked those evoked by electrical stimulation of the perforant path. Both responses were sensitive to the non-N-methyl-D-aspartate glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione. U69593 inhibited responses evoked by perforant path stimulation but had no effect on responses evoked by glutamate application.(ABSTRACT TRUNCATED AT 250 WORDS)

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Idazoxan increases perforant path-evoked EPSP slope paired pulse inhibition and reduces perforant path-evoked population spike paired pulse facilitation in rat dentate gyrus

Brain Research ◽

10.1016/j.brainres.2005.12.020 ◽

2006 ◽

Vol 1072 (1) ◽

pp. 36-45 ◽

Cited By ~ 5

Author(s):

John Knight ◽

Carolyn W. Harley

Keyword(s):

Dentate Gyrus ◽

Population Spike ◽

Perforant Path ◽

Paired Pulse ◽

Paired Pulse Facilitation

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Paired-pulse facilitation in the dentate gyrus: a patch-clamp study in rat hippocampus in vitro

Journal of Neurophysiology ◽

10.1152/jn.1994.72.1.326 ◽

1994 ◽

Vol 72 (1) ◽

pp. 326-336 ◽

Cited By ~ 64

Author(s):

M. Andreasen ◽

J. J. Hablitz

Keyword(s):

Patch Clamp ◽

Dentate Gyrus ◽

Time Constant ◽

Rise Time ◽

Time Course ◽

Nmda Antagonist ◽

Paired Pulse ◽

Stimulation Intensity ◽

Paired Pulse Facilitation ◽

Epsc Amplitude

1. Whole-cell patch-clamp recordings were used to study paired-pulse facilitation (PPF) of the lateral perforant path input to the dentate gyrus in thin hippocampal slices. 2. Orthodromic stimulation of the lateral perforant pathway evoked a excitatory postsynaptic current (EPSC) with a latency of 3.3 +/- 0.1 ms (mean +/- SE) that fluctuated in amplitude. The EPSC had a rise time (10-90%) of 2.79 +/- 0.06 ms (n = 35) and decayed with a single exponential time course with a time-constant of 9.14 +/- 0.24 ms (n = 35). No correlation was found between the amplitude of the EPSC and the rise time or decay time-constant. The non-N-methyl-D-aspartate (NMDA) antagonist 6-cyano-7-nitroquinoxaline-2,3-dione completely blocked the EPSC whereas the NMDA antagonist D-aminophosphonovaleric acid (APV) had modest effects. 3. When a test (T-)EPSC was preceded at an interval of 100 ms by a conditioning (C-)EPSC, a significant increase in the amplitude of the T-EPSC was seen in 38 out of 44 trials analyzed from a total of 27 granule cells. The average amount of PPF was 35.7 +/- 2.1%. There was no apparent correlation between the amount of PPF and the stimulation intensity or mean amplitude of the C-EPSC. The time course of the facilitated T-EPSC was not significantly different from that of the C-EPSC. 4. No correlation was found between the amplitude of the C-EPSC and that of the T-EPSC. Estimates of quantal content (mcv) were determined by calculating the ratio of the squared averaged EPSC amplitude (from 48 responses) to the variance of these responses (M2/sigma 2) whereas quantal amplitudes (qcv) were estimated by calculating the ratio of the response variance to average EPSC amplitude (sigma 2/M). PPF was found to be associated with an average increase in mcv of 64.8 +/- 7.2% (n = 38) whereas qcv was decreased by 12.1 +/- 3.8%. 5. The time course of PPF was studied by varying the interval between the C- and T-pulse from 10 to 400 ms while keeping the stimulation intensity constant. Maximal facilitation of the T-EPSC was obtained with interpulse intervals < or = 25 ms where the average facilitation amounted to approximately 70% (n = 6). The decline of facilitation was nearly exponential and was no longer evident with intervals > 350 ms.(ABSTRACT TRUNCATED AT 400 WORDS

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NMDA receptors have a dominant role in population spike-paired pulse facilitation in the dentate gyrus of urethane-anesthetized rats

Brain Research ◽

10.1016/0006-8993(93)90379-2 ◽

1993 ◽

Vol 604 (1-2) ◽

pp. 273-282 ◽

Cited By ~ 44

Author(s):

Robert M. Joy ◽

Timothy E. Albertson

Keyword(s):

Dentate Gyrus ◽

Nmda Receptors ◽

Dominant Role ◽

Population Spike ◽

Paired Pulse ◽

Paired Pulse Facilitation ◽

Anesthetized Rats

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Presynaptic Group II mGluR Inhibition of Short-Term Depression in the Medial Perforant Path of the Dentate Gyrus In Vitro

Journal of Neurophysiology ◽

10.1152/jn.2001.85.6.2509 ◽

2001 ◽

Vol 85 (6) ◽

pp. 2509-2515 ◽

Cited By ~ 20

Author(s):

John Kilbride ◽

Anthony M. Rush ◽

Michael J. Rowan ◽

Roger Anwyl

Keyword(s):

Dentate Gyrus ◽

Metabotropic Glutamate Receptors ◽

State Level ◽

Perforant Path ◽

Dependent Manner ◽

Short Term ◽

Concentration Dependent Manner ◽

Postsynaptic Response ◽

Group Ii

Inhibition of short-term plasticity by activation of presynaptic group II metabotropic glutamate receptors (group II mGluR) was investigated in the medial perforant path of the dentate gyrus in the hippocampus in vitro. Brief trains of stimulation (10 stimuli at 1–200 Hz) evoked short-term depression of field excitatory postsynaptic potentials (EPSPs). The steady-state level of depression, measured after 10 stimuli, was frequency dependent, increasing between 1 and 200 Hz. Activation of group II mGluR by the selective agonist LY354740 did not alter short-term depression evoked by frequencies up to 10 Hz, but did inhibit short-term depression evoked at higher frequencies in a frequency- and concentration-dependent manner. The time-averaged postsynaptic response (EPSP per unit time) was found to increase linearly with frequency up to ∼20 Hz. At higher frequencies, the response plateaued, thereby becoming independent of frequency. Frequencies above this were differentiated only during the transient postsynaptic response that accompanies changes in firing rates. Activation of presynaptically located group II mGluR increased the frequency at which the EPSP per unit time plateaued up to 30–50 Hz.

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