The interaction of heterogeneous synaptic inputs of neocortical neurons during the effectuation of a conditioned reflex (CR) is reviewed, and hypotheses are advanced concerning the operation of this mechanism during learning. It has been demonstrated that intracortical glutamate connections as well as synaptic connections from extrathalamic structures which send out cholinergic, noradrenergic, and serotoninergic fibers are activated during the effectuation of a CR, in addition to afferent inputs to neurons of the neocortex from the thalamus. The activation of extrathalamic projections to the neocortex during the effectuation of the CR is qualitatively heterogeneous and has temporal peculiarities. In the complex of heterosynaptic influences on the cortical neurons, three consecutive periods are distinguished: the period of interaction of glutamate, acetylcholine, serotonin, and gamma aminobutyric acid (GABA) with unidentified transmitters from thalamic projections; the period of interaction of glutamate and serotonin; and the period of interaction of acetylcholine and norepinephrine. The results of model investigations on giant neurons, in which cholinergic transmission is subjected to heterosynaptic facilitation and blocking by means of serotonin and monoamines, have been reviewed. The hypothesis is advanced that the basic plastic changes occurring during associative learning develop in the secondary, intracortical glutamate inputs of the neurons under the modulating influence of cholinergic, serotoninergic, and noradrenergic inputs. Pavlov's idea regarding the conditioned reflex (CR) as being the result of the association in the neurons of the cerebral cortex of excitatory influences arising in afferent projections during the combination of conditional and unconditional stimulations, has found broad support at the present time among all those who have taken up the problem of learning [12]. In attempting an analysis of the mechanisms of learning at the level of neurons and synaptic and intracellular processes, investigators typically employ models of learning. In recent years analytic studies in this field have been concentrated on two principal models: heterosynaptic sensitization and prolonged posttetanic potentiation. The model of heterosynaptic sensitization was worked out by Kandel and Tauc [37, 38] on the giant neurons of the abdominal ganglion of Aplysia. It has appeared recently that the principal changes occurring during heterosynaptic facilitation take place in the terminals of secondorder sensory neurons due to the modulating influences of serotonin. As it acts through the adenylate cyclase system of the presynaptic ending, serotonin, the secretion of which is elicited by the conditioning stimulus, slows down the exit of potassium ions from the cell, thus prolonging the action potential, and, as a result of this, increases the influx of calcium ions into the cell, which in the final analysis increases the number of quanta of the transmitter secreted by the presynaptic fiber [11, 36]. There is evidence that such heterosynaptic facilitation under the influence of sertotonin, observable in various objects, usually develops in cholinergic synapses [11, 17, 18, 38]. As it has become evident relatively recently, the second model of learning, originally worked out in neurons of the hippocampus [30], and almost at the same time, although less clearly described, in neurons of the neocortex [14], differs substantially from the first model. Learning, according to this model, is accomplished as the result of the combination of prolonged tetanic excitation of the presynaptic input with simultaneous intense depolarization of the postsynaptic cell [34, 58]. Depolarization of the postsynaptic neurons is achieved relatively easily by the passage of a current through a microelectrode introduced into the cell, and is facilitated by the application of GABA blockers which remove the influence on the neurons under investigation of inhibitory synaptic stimuli. NMDA receptors, which are activated by glutamate secreted from the presynaptic fibers, participate in the development of prolonged posttetanic potentiation. Against the background of the depolarization of the postsynaptic neuron, this transmitter in particular promotes the passage into the postsynapfic cell of calcium ions, which leads to a selective increase in the sensitivity of the neuron to the synaptic input previously activated by means of tetanization. But the increase in the effectiveness of glutamate itself develops due to an increase in sensitivity to it following