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| Paolo Calabresi |
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Clinica Neurologica, Dipartimento di Neuroscienze, Facoltą di Medicina e Chirurgia, Universitą degli Studi di Roma "Tor Vergata", Via di Tor Vergata, 135
00133 - Roma - Italy
e-mail: calabre@uniroma2.it |
Presentation: |
| 2002-10-08, 12:15-13:00 |
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| Dopaminergic control of brain synaptic plasticity. |
| Paolo Calabresi, Diego Centonze, Antonio Pisani, Giorgio Bernardi | |
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Clinica Neurologica, Dipartimento di Neuroscienze, Universitą "Tor Vergata"
& IRCCS Fondazione Santa Lucia, Rome, Italy |
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| Most parts of the central nervous system contain dopamine (DA), a monoamine neurotransmitter released by axon terminals of midbrain neurons of the substantia nigra and ventral tegmental area. The importance of DA in complex motor and cognitive activities is evident in Parkinson's disease, in which the degeneration of nigrostriatal terminals results in severe motor deficits. Moreover, DA plays a critical role in motor learning, reward and drug addiction. The cellular mechanisms underlying these behavioural functions are represented by DA-dependent long-term synaptic changes in various brain areas.
Glutamatergic and nigral dopaminergic afferents impinge on projection spiny neurons of the striatum, providing the most significant inputs to this structure. Isolated activation of glutamate or dopamine (DA) receptors produces short-term effects on striatal neurons, whereas the combined stimulation of both glutamate and DA receptors is able to induce long-lasting modifications of synaptic excitability. Repetitive stimulation of corticostriatal fibres, in fact, causes a massive release of both glutamate and DA in the striatum and, depending on the glutamate receptor subtype preferentially activated, produces either long-term depression (LTD) or long-term potentiation (LTP) of excitatory synaptic transmission. D1-like and D2-like DA receptors interact synergistically to allow LTD formation, while they operate in opposition during the induction phase of LTP. Corticostriatal synaptic plasticity is severely impaired after chronic DA-denervation and requires the stimulation of DARPP-32, a small protein expressed in dopaminoceptive spiny neurons which acts as a potent inhibitor of protein phosphatase-1. |
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