NMDA INDEPENDENT LTP BY ADENOSINE A2 RECEPTOR-MEDIATED
POSTSYNAPTIC AMPA POTENTIATION IN HIPPOCAMPUS
Kofi Kessey and David J. Mogul
Neurobiology & Physiology and Biomedical Engineering
Northwestern University, Evanston, IL 60208 USA
APStracts 4:0088N, 1997.
ABSTRACT
The role of adenosine A2 receptors in normal synaptic transmission and
tetanus- induced long-term potentiation (LTP) was tested by stimulation of the
Schaffer collateral pathway and recording of the field excitatory postsynaptic
potential (EPSP) in the CA1 region of rat transverse hippocampal slices.
Activation of adenosine A2 receptors with the A2 agonist DPMA (20 nM) enhanced
synaptic transmission during low-frequency test pulses (0.033 Hz). Paired
stimulation before and during DPMA exposure indicated no paired-pulse
faciliation as a result of A2 activation suggesting that enhancement was not a
result of presynaptic modulation. DPMA enhanced the early phase AMPA component
of the EPSP. In contrast, DPMA had no effect on the NMDA component isolated
using low extracellular Mg2+ and the AMPA receptor blocker CNQX (20 æM)
indicating that the effects of A2 activation on synaptic transmission were
mediated by a postsynaptic enhancement of the AMPA response. Activation of
adenosine A2 receptors during a brief tetanus (100 Hz, 1s) increased the level
of LTP by 36% over that seen in response to a tetanus under control
conditions. DPMA exposure after prior induction of LTP showed no additional
potentiation indicating that the mechanisms that contribute to both types of
increases in synaptic transmission share a common mechanism. A slow onset
NMDA-independent LTP could be induced by application of a tetanus during
perfusion of DPMA with the NMDA blocker AP5 (50 æM). Blockade of L-type Ca
channels with nifedipine (10 æM) had no effect on normal synaptic transmission
but reduced NMDA-independent LTP by 32%. Very little NMDA-independent LTP
could be induced following prior saturation of NMDA-dependent LTP via multiple
tetani spaced 10 min apart indicating that both forms of LTP are ultimately
convergent on a common mechanism, presumably the postsynaptic AMPA receptor
response. Because extracellular adenosine levels are modulated by cellular
activity throughout the brain and since adenosine receptor activation can
markedly alter levels of synaptic transmission independent of NMDA receptors,
adenosine may play an important and complex role as a modulator of synaptic
transmission in the brain.
Received 30 September 1996; accepted in final form 9 June 1997.
APS Manuscript Number J787-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 15 July 1997