Synaptic depression: a dynamic regulator of synaptic communication with varied functional roles

It appears that a bewildering array of processes can contribute to the mechanism of synaptic depression. Markram and Tsodyks argued that the depression they observed in cortical cells was probably dependent on the amount of transmitter released, as indicated in the model (Fig. 1Fig. 1), although changes in the affinity of postsynaptic glutamate receptors could not be excluded[9xMarkram, H. and Tsodyks, M. Nature. 1996; 882: 807–810Crossref | Scopus (510)See all References[9]. However, in studies of the visual cortex several postsynaptic factors have been eliminated because synaptic depression at excitatory synapses is unaffected by postsynaptic receptor blockade with the non-NMDA receptor antagonist CNQX or by reduction of receptor desensitization by cyclohexemide (J.A. Varela et al., unpublished observations). In developing muscle afferent–motoneuron contacts a presynaptic mechanism for depression has also been implicated because depression is abolished when transmitter release is decreased by low extracellular Ca2+ concentrations or bath-application of the GABAB agonist, baclofen[5xLev-Tov, A. and Pinco, M. J. Physiol. 1992; 447: 149–169Crossref | PubMedSee all References[5]. In cultured spinal cord neurons transmitter depletion is probably also responsible for synaptic depression at some synapses. However, at other synapses in such cultures, the depression might be due to failure of the presynaptic action potential to invade all of the terminals[6xStreit, J., Luscher, C., and Luscher, H-R. J. Neurophysiol. 1992; 68: 1793–1803PubMedSee all References[6]. It has also been proposed that synaptic depression might be caused by a form of negative feedback. This can occur if excess transmitter leaks from synaptic sites to engage presynaptic autoreceptors which decrease transmitter release[8xDeisz, R.A. and Prince, D.A. J. Physiol. 1989; 412: 513–541PubMedSee all References, 21xScanziani, M. et al. Nature. 1997; 385: 630–634Crossref | PubMed | Scopus (357)See all References], or by an activity-dependent reduction in the presynaptic calcium currents responsible for transmitter release[22xJia, M. and Nelson, P.G. J. Neurophysiol. 1986; 56: 1257–1267PubMedSee all References[22]. Finally, alterations in the sensitivity of postsynaptic receptors have also been implicated in synaptic depression[23xNumann, R.E. and Wong, R.K. Neurosci. Lett. 1984; 47: 289–294Crossref | PubMed | Scopus (58)See all References[23].It should be clear from this review that synaptic depression has the potential to be an important contributor to the properties and function of networks. But are these interesting properties actually engaged in active networks? This will be a difficult question to answer because it will require modifying the degree of synaptic depression within a network and documenting the effects on the network output. This may be easier to accomplish in rhythmically active networks whose output can be easily measured. It will be considerably more difficult to establish whether or not synaptic depression actually enhances the dynamic sensitivity of networks, both for experimental reasons and because we do not know how such information is actually used in functioning networks.Finally, it will be important in future studies to establish whether synaptic depression is actively regulated by the nervous system and whether or not its effects can be modified by events in the postsynaptic cell. For example, it is possible that active conductances in dendrites might be capable of compensating or modifying the effects of depression at some synapses.Perhaps many different classes of synapse can express both depression and facilitation. Certainly, there is evidence that both processes can be co-expressed at the same synapse. Can the nervous system control the relative expression of either process at individual synapses? Is synaptic depression a property that is regulated retrogradely by the postsynaptic cell, as has been proposed for developing synapses in the spinal cord[24xSeebach, B.S. and Mendell, L.M. J. Neurophysiol. 1996; 76: 3875–3885PubMedSee all References[24]?