cells, respectively, underlies the opposite Ca
2 +
-de- pendent modification rules for these structures
Silkis, 1999. This assumption is based on the data that cGMP concentration is down-regulated
by Ca
2 +
calmodulin Baltrons et al., 1997, while the increase in cAMP level is positively correlated
with Ca
2 +
rise. We have proposed that the rise in cGMP level could be provided not only by NO
action on soluble guanylate cyclase Linden, 1994; Daniel et al., 1998, but also by the activation of
membrane-bound guanylate cyclase via GABAb receptors Silkis, 1998. Our preliminary experi-
mental data support this hypothesis Silkis et al., 1998.
To provide the fulfillment of the Hebbian rule, we have postulated that only receptors activated
by a transmitter are modifiable. This postulate corresponds with the data that artificial rise of
intracellular Ca
2 +
level or increase in protein kinase activity does not lead to a change in phos-
phorylation state to LTP or LTD in the absence of synaptic activation Nakazawa et al., 1995;
Otsu et al., 1995; Wu et al., 1998. Using the computational model of postsynaptic processes,
we have found that the Hebbian rule the coinci- dence of pre- and postsynaptic cell activity is the
only necessary condition for synaptic plasticity. Modification of simultaneously activated excita-
tory and inhibitory inputs, such as LTPe together with LTDi, or LTDe together with LTPi can be
obtained only due to variations in pre- andor postsynaptic cell activity. The sign of modification
LTP or LTD is determined by the shift positive or negative in the ratio between active protein
kinases and phosphatases in relation to the ratio produced by prior stimulation Silkis, 1998.
3. Necessary conditions for the modifications of synapses on different cerebellar cells
The arrangement of excitatory and inhibitory inputs to different cells of olivary-cerebellar net-
works is summarized in Table 1. The examination of known experimental data have shown that
postsynaptic membranes of excitatory synapses at different cerebellar cells contain NMDA recep-
tors, mGlu receptors and AMPA receptors with high permeability for Ca
2 +
ions, while inhibitory synapses
contain postsynaptic
GABAa and
GABAb receptors Table 2. The presence of voltage-dependent Ca
2 +
channels on different cerebellar neurones was also demonstrated. Based
on these data, we have assumed that necessary conditions for the changes in protein kinases and
protein phosphatase activity, and subsequent synaptic modification, are fulfilled for all elements
of olivary-cerebellar network. Since cGMP is ex- pressed in granule cells GCs and DCNCs, and
since GABAb receptors are found on these cells, we used identical modification rules for PCs, GCs
and DCNCs. Another cyclic nucleotide, cAMP, is probably expressed in Golgi cells due to the pres-
ence of type II mGlu receptors on these cells
Table 1 The organization of excitatory excit and inhibitory inhib inputs to cerebellar cells
Type of cell Inputs to cerebellar cells
Cerebellar cells From excitatory fibers
From axon terminals of inhibitory cells MF
CF PF
PC Golgi
Stellatebasket Lugaro
inhib excit
Granule cell input Excitatory
inhib excit
excit DCNCe output
excit Inhibitory
Purkinje cell inhib
inhib excit
excit excit
excit inhib
inhib Golgi cell
excit inhib
inhib inhib
Stellatebasket cells excit
Lugaro cell inhib
excit inhib
excit DCNCi
Table 2 Receptors and channels at postsynaptic membranes of excitatory and inhibitory synapses on different cerebellar cells
a
Cerebellar cells Ca
2+
channels Receptors
Cyclic nucleotides GABA sensitive
Glutamate sensitive NMDA
mGlu GABAa
GABAb cGMP
cAMP AMPA
1 2
1 Granule cell
3 1
4 5
DCNCe 6
7 ?
8 9
7 10
Purkinje cell 11
12 11
11 13
11 11
14 15, 16
+ 1
Golgi cell 16?
14 2
Stellatebasket cells +
17 ?
2 15
+ Lugaro cell
? DCNCi
+ +
a
1, Maex and De Schutter 1998; 2, Grandes et al. 1994; 3, Barthel et al. 1996; 4, D’Angelo et al. 1997; 5, Poulopoulou and Nowak 1998; 6, Audinat et al. 1990; 7, Sastry et al. 1997; 8, Morishita and Sastry 1993; 9, Mouginot and Gahwiler 1995;
10, Biggio and Guidotti 1976; 11, Daniel et al. 1998; 12, Yuzaki et al. 1996; 13, Batchelor and Garthwait 1992; 14, Scherzer et al. 1997; 15, Hamori et al. 1996; 16, Knoflach and Kemp 1998; 17, Bureau and Mulle 1998; +, the expression of receptors
is defined by presence of presynaptic terminals.
Neki et al., 1996. We assume that modification rules for inhibitory Golgi, stellate, basket and
Lugaro interneurones can be taken identical to those of hippocampalneocortical cells.
4. Interrelated modifications in the efficacy of excitatory and inhibitory synapses in
