Functions of the cerebral cortex and cholinergic systems in synaptic plasticity induced by sensory preconditioning

Abstract

This thesis provides evidence to support the hypothesis that synaptic plasticity in the primary somatosensory cortex is a cellular correlate of associative learning, that the process depends upon acetylcholine and that only certain cortical neurons display this plasticity. In a first series of experiments, single-imit recordings were carried out in the barrel cortex of awake, adult rats subjected to whisker pairing, an associative learning paradigm where deflections of the recorded neuron's principle vibrissa were repeatedly paired with those of a non-adjacent one. On average, this form of sensory preconditioning increased the responses of a recorded unit to the stimulation of the non-adjacent vibrissa. In contrast, following explicitly unpaired control experiments, neuronal responsiveness decreased. The effect of pairing was further enhanced by local, microiontophoretic delivery of NMDA and the nitric oxide synthase inhibitor L-NAME and reduced by the NMDA receptor competitive antagonist AP5. These results and the fact that the influence of the pharmacological agents on neuronal excitability were either transient (liinited to the delivery period) or simply absent indicated that the somatosensory cerebral cortex is one site where plasticity emerges following whisker pairing. In subsequent experiments, using a similar conditioning paradigm that relied on evoked potential rather than single-unit recordings, increases in the responses of cortical neurons to the non-adjacent whisker were blocked by atropine sulfate, an antagonist of muscarinic cholinoreceptors. Administration of norn-ial saline or atropine methyl nitrate, a muscarinic antagonist that did not cross the blood-brain barrier, instead of atropine sulfate, did not affect plasticity. Analysis of the behavioral state of the animal showed that the changes observed in the evoked potential could not be attributed to fluctuations m the behavioral state of the animal. By combining the results described in this thesis with data foimd in related literature, the author hypothesizes that whisker pairing induces an acetylcholine-dependent form of plasticity within the somatosensory cortex through Hebbian mechanisms.