A subset of neurons of the auditory brainstem is highly specialized to perform processing tasks where the precise temporal registration between presynaptic and postsynaptic spike trains is functionally important. One specialization in these neurons is the presence of a low-threshold potassium conductance in the cell membrane. The conductance seen in these cells differs from conventional mammalian delayed rectifiers in that it has a particularly low activation voltage (-70 mV), and differs from other potassium conductances active near rest (""""""""A"""""""" currents) in that it is non- inactivating. This (or a similar) conductance has been identified in cells from several nuclei of the brainstem auditory system. This conductance is functionally important because it endows the postsynaptic with a low resting input resistance and a short time constant that limits temporal summation of synaptic potentials. The experiments in this project investigate the characteristics of this conductance through investigation of 3 specific aims. In the first aim, we will test the hypothesis that the low-threshold conductance in ventral cochlear nucleus neurons is mediated by a single kind of potassium channel with first order kinetics. We will make single- channel recordings from on-cell patches on acutely isolated cells from adult guinea pig and from identified neurons in rat brain slices. The kinetics, voltage-dependence, and pharmacological sensitivity to blockers will be evaluated. These experiments will extend our knowledge of this specialized channel. In the second aim, we will investigate the hypothesis that the properties of the low-threshold conductance, like many other potassium conductances, can be modulated by protein kinase activity. We will specifically examine modulation of the voltage-dependence and kinetics of the conductance by protein kinase A and phosphatases. We will verify the routes of activation using specific kinase inhibitors. We will also attempt to determine which neurotransmitters are coupled to these kinases. In the third aim, we will examine the regulation of the expression of the low-threshold conductance during development, and by afferent innervation.We will physiologically measure the density (nS/pF) of the low threshold conductance as a function of developmental age in brain slices from rat pups. We will also measure the density of the conductance in cells in primary culture and in coculture with spiral ganglion cells to test the idea that the expression is regulated by afferent input. In the last part of this aim, we will measure the expression of the conductance in acutely isolated cochlear nucleus neurons after ablation of the cochlea. These experiments will clarify the role of the low-threshold conductance in ventral cochlear nucleus neurons. Studies of the regulation of this conductance by afferent input are relevant to the clinical issues of central auditory system function after peripheral damage.
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