BioSystems 57 2000 187 – 196
The cortico-basal ganglia-thalamocortical circuit with synaptic plasticity. I. Modification rules for excitatory and
inhibitory synapses in the striatum
Isabella Silkis
Neurophysiology of Learning Laboratory, Institute of Higher Ner6ous Acti6ity and Neurophysiology of the Russian Academy of Sciences, Butlero6a
5
a str.,
117865
Moscow, Russia Received 25 July 2000; accepted 28 August 2000
Abstract
It is pointed out that Ca
2 +
-dependent modification rules for NMDA-dependent NMDA-independent synaptic plasticity in the striatum are similar to those in the neocortex and hippocampus cerebellum. A unitary postsynaptic
mechanism of synaptic modification is proposed. It is based on the assumption that, in diverse central nervous system structures, long-term potentiationdepression LTPLTD of excitatory transmission depressionpotentiation of
inhibitory transmission, LTDiLTPi is the result of an increasingdecreasing the number of phosphorylated AMPA and NMDA GABA
A
receptors. According to the suggested mechanism, Ca
2 +
calmodulin-dependent protein kinase II and protein kinase C, whose activity is positively correlated with Ca
2 +
enlargement, together with cAMP-depen- dent protein kinase A cGMP-dependent protein kinase G, whose activity is negatively correlated with Ca
2 +
rise mainly phosphorylate ionotropic striatal receptors, if NMDA channels are opened closed. Therefore, the positive
negative post-tetanic Ca
2 +
shift in relation to a previous Ca
2 +
rise must cause NMDA-dependent LTP + LTDi LTD + LTPi or NMDA-independent LTD + LTPiLTP + LTDi. Dopamine D
1
D
2
or adenosine A
2A
A
1
receptor activation must facilitate LTP + LTDiLTD + LTPi due to an augmentinglowering PKA activity. Activation of
muscarinic M
1
M
4
receptors must enhance LTP + LTDiLTD + LTPi as a consequence of an increasedecrease in the activity of protein kinase CA. The proposed mechanism is in agreement with known experimental data. © 2000
Elsevier Science Ireland Ltd. All rights reserved.
Keywords
:
LTP; LTD; Striatum; Dopamine; Adenosine; Acetylcholine www.elsevier.comlocatebiosystems
1. Introduction
It is widely believed that an activity-dependent modification in the efficacy of synaptic transmis-
sion provides an important key to understanding the cellular mechanisms of learning and memory.
Tel.: + 7-95-3344345; fax: + 7-95-3388500. E-mail address
:
isabella-silkismtu-net.ru I. Silkis. 0303-264700 - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 3 0 3 - 2 6 4 7 0 0 0 0 1 3 4 - 9
Such forms of plasticity as long-term potentiation LTP and long-term depression LTD in the
efficacy of excitatory transmission, and inhibitory transmission LTPi, LTDi, have been obtained in
the neocortex, hippocampus, cerebellum, basal ganglia and other structures of the central ner-
vous system CNS. It has been found that Ca
2 +
- dependent changes in the activity of protein
kinases PKs and protein phosphatase 1 PP1 are necessary for synaptic modification in these
structures Calabresi et al., 1992, 1994, 1999b; Bear and Malenka, 1994; Pisani et al., 1997;
Daniel et al., 1998. The relatively highlow post- synaptic Ca
2 +
elevation usually causes neocorti- cal or hippocampal LTPLTD and cerebellar
LTDLTP Bear and Malenka, 1994; Hartell, 1994. In the neocortex or hippocampus cerebel-
lum, LTDi induction requires an additional Ca
2 +
lowering elevation compared with the Ca
2 +
level that causes LTPi for a review, see Silkis, 1998. Therefore, Ca
2 +
-dependent modifi- cation rules for excitatory and inhibitory synapses
are opposite. We have explained the diverse Ca
2 +
-dependent modification rules for the neocortical hippocampal and cerebellar cells by expression of
different cyclic nucleotides, cAMP and cGMP, respectively Silkis, 2000a,b.
In the striatum, the input structure of the basal ganglia, experimentally observed Ca
2 +
depen- dence of LTP and LTD looks contradictory. On
the one hand, it has been demonstrated that the highlow Ca
2 +
elevation is required for LTD LTP Calabresi et al., 1992, 1994. On the other,
LTP induction had been facilitated by diverse protocols that led to additional Ca
2 +
rise Cal- abresi et al., 1997; Pisani et al., 1997. The mecha-
nism explaining
these controversial
results remains unknown. In addition, the sign of synap-
tic modification in the striatum essentially de- pends on the activation of different types of
receptors sensitive to dopamine, adenosine and acetylcholine Calabresi et al., 1994, 1997, 1999a;
Hernandes-Lopez et al., 1997. However, the mechanism of participation of these modulatory
neurotransmitters in striatal plasticity is not clearly understood.
The aim of this work has been to analyze the possible mechanisms underlying experimentally
found features of striatal LTPLTD. We analyzed the role of NMDA receptor activation in the
Ca
2 +
dependence on the sign of synaptic modifi- cation and modulatory role of dopamine D
1
D
2
, adenosine A
1
A
2A
and acetylcholine muscarinic M
1
M
4
receptor activation in synaptic plasticity. An earlier suggested unitary postsynaptic mecha-
nism of plasticity Silkis, 1998, 2000a,b provided the basis for this analysis.
2. The proposed mechanism for synaptic plasticity in striatal spiny cells
