The Journal of Neuroscience, July 15, 1999, 19(14):6102-6110
Glutamate-Triggered Events Inducing Corticostriatal Long-Term
Depression
Paolo
Calabresi1, 2,
Diego
Centonze1,
Paolo
Gubellini1, 3,
Girolama A.
Marfia1, and
Giorgio
Bernardi1, 2
1 Clinica Neurologica, Università di Roma Tor
Vergata, 00133 Rome, Italy, 2 IRCCS Ospedale, Santa
Lucia, 00176 Rome, Italy, and 3 Istituto di Medicina
Sperimentale, Consiglio Nazionale delle Ricerche, 00133 Rome,
Italy
Repetitive activation of corticostriatal fibers produces long-term
depression (LTD) of excitatory synaptic potentials recorded from
striatal spiny neurons. This form of synaptic plasticity might be
considered the possible neural basis of some forms of motor learning
and memory. In the present study, intracellular recordings were
performed from rat corticostriatal slice preparations to study the role
of glutamate and other critical factors underlying striatal LTD. In
current-clamp, but not in voltage-clamp experiments, brief focal
applications of glutamate, as well as high-frequency stimulation (HFS)
of corticostriatal fibers, induced LTD. This pharmacological LTD
and the HFS-induced LTD were mutually occlusive, suggesting that both
forms of synaptic plasticity share common induction mechanisms.
Isolated activation of either non-NMDA-ionotropic glutamate receptors
(iGluRs) or metabotropic glutamate receptors (mGluRs), respectively by
AMPA and t-ACPD failed to produce significant long-term
changes of corticostriatal synaptic transmission. Conversely, LTD was
obtained after the simultaneous application of AMPA plus t-ACPD. Moreover, also quisqualate, a compound that
activates both iGluRs and group I mGluRs, was able to induce this form
of pharmacological LTD. Electrical depolarization of the recorded neurons either alone or in the presence of t-ACPD and
dopamine (DA) failed to mimic the effects of the activation of
glutamate receptors in inducing LTD. However, electrical depolarization was able to induce LTD when preceded by coadministration of
t-ACPD, DA, and a low dose of hydroxylamine, a compound
generating nitric oxide (NO) in the tissue. None of these compounds
alone produced LTD. Glutamate-induced LTD, as well as the HFS-induced
LTD, was blocked by L-sulpiride, a D2 DA receptor
antagonist, and by 7-nitroindazole monosodium salt, a NO
synthase inhibitor. The present study indicates that four main factors
are required to induce corticostriatal LTD: (1) membrane depolarization
of the postsynaptic neuron; (2) activation of mGluRs; (3) activation of
DA receptors; and (4) release of NO from striatal interneurons.
Key words:
dopamine; excitatory amino acids; nitric oxide; metabotropic glutamate receptors; motor learning; striatum
Copyright © 1999 Society for Neuroscience 0270-6474/99/19146102-09$05.00/0
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