An in vitro electrophysiologic analysis of the effect of nicotinic receptor activation on synaptic transmission and membrane properties in layer II--III rat auditory cortex

The experiments detailed in this dissertation examine the role of nicotinic acetylcholine receptors in modulating synaptic transmission and neuronal membrane properties in the auditory cortex. Understanding the function of nicotinic receptors in the cortex is of particular importance since nicotinic receptors have been implicated in cognition, attention, learning and memory. Furthermore, studies have reported decreased amounts of nicotinic receptors in the cortex of patients with Alzheimer's disease. Also, of clinical importance is nicotine addiction.; The experiments in this proposal make use of an in vitro preparation. Field potential and whole cell recordings were made from layer II-III pyramidal neurons of the auditory cortex. The susceptibility of glutamatergic and GABAergic synaptic potentials evoked by white matter stimulation to modulation by nicotinic receptor agonists, nicotine and choline (an alpha-7 nicotinic receptor subtype), was examined. The effect of these agonists were also examined on neuronal firing rates and membrane properties.; The major findings of this work can be summarized as follows. (1) Application of nicotinic agonists depolarized the membrane potential (2) Nicotinic agonists also directly enhanced the AMPA/kainate, NMDA, and GABAA receptor-mediated responses. (3) Nicotinic-modulation of synaptic potentials was due to presynaptic activation of nicotinic receptors. (4) The nicotinic agonists also resulted in increased firing rate of pyramidal neurons to a depolarizing current pulse. (5) The increased firing rate was due to agonist reduction of the medium afterhyperpolarization. (6) Nicotinic-mediated effects on increased firing rate were postsynaptic. (7) All the above-mentioned effects by nicotinic agonists were long-lasting and mediated through activation of the alpha7 nicotinic receptors.; In conclusion, these results indicate that nicotinic receptors are involved in modulating glutamatergic and GABAergic synaptic potentials and enhanced firing rate. The overall effects of nicotine on synaptic potentials and neuronal membrane properties are excitatory, which may lead to increased attention and cognitive abilities.