Intracellular studies on cortical synaptic plasticity. Conditioning effect of antidromic activation on test-EPSPs.

1. An intracellular study on pyramidal tract (PT) neurons in the cat's motor cortex was carried out to examine whether their antidromic activation would be able to induce plastic changes in the efficacy of the synapses situated on their membrane. 2. The experimental paradigm was based on the principles of classical conditioning. It included habituation, pseudoconditioning, conditioning and extinction procedures. The antidromic spike was regarded as an unconditioned stimulus while excitatory postsynaptic potentials (EPSPs) evoked by thalamic (n. ventralis lateralis), callosal and somatosensory afferents served as conditioned stimuli. Stimulus pairs were given, consisting of EPSPs and antidromic spikes with various time intervals, and the stimulus sequences were at a 0.2--1.0/s frequency. 3. Reversible, short-term (3--28 min) enhancement of synaptic excitability was observed in 27% of the PT cells after conditioning with 60--150 stimulus pairs. 4. EPSP-spike and spike-EPSP sequences were equally effective, but plastic changes were induced only by stimulus pairs with less than 100 ms interstimulus intervals. 5. Facilitated EPSP states were frequently accompanied by changes in membrane potential, membrane resistance and firing activity. 6. In repeated conditioning series, the temporal parameters of conditioning changes, the number of stimuli necessary for full development of facilitation, and some membrane parameters showed marked alterations. 7. Conditioned plastic changes in synaptic efficacy showed analogies with associative learning: (a) they were specific to the pairing procedure, because randomized presentation of EPSPs and antidromic spikes never produced synaptic facilitation; (b) unpaired spike trains used as unconditioned stimuli (of 10--200/s frequency and 1--20 s duration) caused only a minor degree of facilitation as compared with EPSP-spike pairings; (c) changes in synaptic efficacy were subject to extinction. 8. The present findings indicate that the plastic changes in synaptic transmission may be localized to the postsynaptic membrane of the conditioned PT cells.