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
olivary-cerebellar network
It is significant that input signal incoming via MFs simultaneously activates GCs, input cells of
cerebellar cortex input layer of the network, and excitatory DCNCs DCNCes, output cells of cere-
bellum output layer of the network Fig. 1. Being transformed by the GC signal affects PCs
and numerous cerebellar inhibitory interneurones, such as Golgi, stellate, basket and Lugaro cells via
PFs. Every cell of the network is not only excited, but also inhibited Table 1. Usually, models of
cerebellar network do not make any allowance for this fact. Thus, inhibition of Golgi cell by Lugaro
interneuron was not considered in the model of the input layer of cerebellum Maex and De Schutter,
1998. Cerebellar interneurones inhibit each other providing the basis for disinhibition. This effect
was also left out of the account in models of learning.
It follows from suggested mechanism of plastic- ity that changes in the efficacy of simultaneously
activated excitatory and inhibitory synaptic inputs to a cell are interrelated. The strengthening atten-
uation of inhibition of PCs, GCs and DCNCs causes a decrease increase in postsynaptic Ca
2 +
level, increase decrease in PKG activity, receptor phosphorylation dephosphorylation, and simul-
taneous induction of LTPe together with LTDi LTDe together with LTPi. On the contrary, the
strengthening attenuation of inhibitory inputs to cerebellar interneurones causes a decrease in-
crease in Ca
2 +
level and inhibition activation of PKA, dephosphorylation phosphorylation of re-
ceptors, and simultaneous induction of LTDe to- gether with LTPi LTPe together with LTDi. The
conversion of input signal by GC is influenced by inhibitory Golgi cell, while the modification of the
same input signal arriving to output DCNCe is controlled by inhibitory PC Fig. 1. Thus, trans-
formations of input signals at different layers of olivary-cerebellar network are interrelated since
GCs activate PCs that in turn inhibit Golgi cells.
Other external signals incoming from inferior olive IO via CF and its collaterals simultaneously
activate PCs, DCNCes, inhibitory DCNCs DCN- Cis, Golgi cells and basket cells Fig. 1. Addi-
tional depolarization
of Golgi
cells, PCs
and DCNCs must affect synaptic efficacy. Thus, the character of simultaneous modification of
synapses at different layers of cerebellar network depends on the presence of a signal from IO.
Proposed long-term bidirectional changes in the efficacy of diverse cerebellar synapses are summa-
rized in Table 3. In turn, the activity of neurons in IO is influenced by cerebellar cells Fig. 1. Thus,
DCNCis inhibit olivary neurones, while DCNCes interpositus, for example excite olivary cells via
mesodiencefalic nuclei red nucleus, for example. Cells of red nucleus activate also DCNCes, form-
ing a reverberation loop and supporting modifica- tion of synapses on DCNCes.
A signal from IO is considered as a training signal. It could teach PCs to recognize specific
pattern of input signals Marr, 1969 or train PCs to reduce error Albus, 1971. With respect to
conventional opinion, the rise of output cerebellar signal requires CF activity, since this rise is the
consequence of associative LTDe in the PF – PC pathway and disinhibition of DCNCes. However,
such an effect is inconsistent with experimentally found data that activity of olivary cells is inhib-
ited during the reaching and all phases of the behavior Horn et al., 1998. Unlike, according to
our model, induction of LTPe in PF – PC synapses that occurs in the absence of a CF activity, this
could cause an increase of inhibition of DCNCes, and advance LTP of excitatory inputs from MFs
to DCNCes. Thus, a potentiation of output cere- bellar signal increase in the rate of DCNCes
discharges could be induced only during the si- lence of olivary neurones. This result is in a good
accordance with the aforementioned experimental data Horn et al., 1998.
Neural networks with numerous interconnected inhibitory cells have been implicated in the gener-
ation of high-frequency oscillations Whittington et al. 1995. The olivary-cerebellar network in-
cludes different reciprocally connected inhibitory neurones Fig. 1. Frequency of oscillations pro-
duced by this network tends to shift to lower frequencies after an inhibition of GABAa recep-
tors on IO cells decrease of inhibition of IO cells Lang et al., 1996. This result leads us to the
assumption that external stimulation andor DC- NCis discharges that cause inhibition of IO cells
could result in a rise in the frequency of oscillations.
5. The comparison with known experimental data
