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Monoaminergic modulation of physiological responsiveness, intrinsic input-output functioning and persistent inward currents of mammalian ventral horn interneurons

Posted on:2006-12-08Degree:Ph.DType:Dissertation
University:Northwestern UniversityCandidate:Theiss, Renee DianeFull Text:PDF
GTID:1454390008463453Subject:Biology
Abstract/Summary:
Spinal interneurons are essential integrators of synaptic transmission for motor control, receiving abundant descending input from the brain and brainstem as well as afferent information from the periphery. Monoaminergic modulation of functionally classified spinal interneurons, determined by responses to transient input in vivo, has been extensively studied. Studies of monoaminergic influence on responses to sustained physiological input and intrinsic firing properties, however, were lacking. Our initial in vivo study demonstrated that adult cat lumbar interneurons, recorded extracellularly, were capable of rhythmic firing in response to sustained physiological input, and blocking monoaminergic input suppressed firing in cells with strong muscle spindle Ia afferent input, but enhanced firing in interneurons with weak Ia input. Further studies, in in vitro lumbar cord slices from juvenile rats, revealed that these ventral horn interneurons, recorded intracellularly, formed electrophysiologically heterogeneous populations with distinct firing patterns: repetitive-firing, initial-burst and single-spiking. Monoamine modulation of the input-output functions was mixed. Highly excitable cells were inhibited, while less excitable cells were facilitated. Whole-cell patch recordings in similar slices revealed differences in persistent inward currents (PICs). Among the distinct firing patterns, strong PICs with a dominant persistent sodium component (Nap) produced repetitive-firing. Initial-burst cells had moderate PICs, also composed of Nap, though additional currents likely contribute to the bursts. Single-spiking cells had little to no PICs, and block of Nap converted repetitive-firing patterns to single spikes. Monoaminergic effects on a restricted sample of repetitive-firing cells were modest, though the descending PIC significantly increased but without correlation to changes in firing properties. We concluded that the predominant determinant of firing pattern in response to sustained input was the amplitude of the Nap PIC. Monoaminergic modulation was related to the strength of Ia afferent input as well as initial intrinsic excitability. We speculate that intrinsic firing properties and their monoaminergic modulation contribute to the integrative capacity of ventral horn interneurons, allowing them to faithfully respond to changing sustained inputs.
Keywords/Search Tags:Input, Interneurons, Monoaminergic modulation, Ventral horn, Intrinsic, Currents, Firing, Physiological
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