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Dissertation
Psychostimulant drug effects on electrophysiological indices of early stage sensory processing and rodent performance of a visual signal detection task
Doctor of Philosophy (Ph.D.), Drexel University
2016
DOI:
https://doi.org/10.17918/etd-7158
Abstract
Methylphenidate (MPH) is a psychostimulant drug used clinically to treat ADHD and off-label as a performance enhancing agent in healthy individuals. MPH enhances catecholamine transmission via blockade of norepinephrine (NE) and dopamine (DA) reuptake transporters. However, it is unclear how blockade of catecholamine reuptake impacts neural circuits responsible for cognitive and sensorimotor function to result in performance enhancement. Optimal detection of sensory information is critical for cognitive and motor actions and overall performance enhancement may significantly rely on improvements in processing incoming sensory stimuli. The locus coeruleus (LC)-NE system regulates state dependent transmission of sensory signals. The rat dorsal lateral geniculate nucleus (dLGN) is the primary thalamic relay for visual information from the retina to the visual cortex and output from the LC-NE system facilitates dLGN neuronal responses to afferent input. Selective attention to incoming stimuli also enhances LGN responsiveness during successful performance of sensory-guided goal-directed behaviors. The hypothesis tested in the current work is that psychostimulant agents, such as MPH, that increase NE neurotransmission and improve attention should enhance stimulus-evoked neuronal responsiveness to visual stimuli within the rat dLGN and behavioral outcomes during performance of a visual signal detection task. Initial electrophysiological experiments demonstrated MPH enhancement of dLGN neuronal responses to light stimuli in the anesthetized rat. To investigate the relevance of these findings to dynamic conditions that exist in waking animals, MPH was evaluated for its potential to alter dLGN responsiveness and behavioral outcomes during performance of a visual signal detection task. Rats were trained to indicate by lever press whether light stimuli were detected. MPH enhanced properties of light-evoked activity within individual neurons, ensembles of neurons, and visually-evoked potentials in response to light stimuli that guided performance within the task. MPH also improved reaction times to make correct responses during task performance. Further, it was demonstrated by immunostaining that catecholaminergic innervation to the dLGN is solely noradrenergic. This work suggests that MPH, acting via noradrenergic mechanisms, can substantially impact early stage sensory signal processing and subsequent behavioral outcomes. Sensory enhancement may be a significant component of psychostimulant-induced performance enhancement in ADHD patients and healthy individuals.
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Details
- Title
- Psychostimulant drug effects on electrophysiological indices of early stage sensory processing and rodent performance of a visual signal detection task
- Creators
- Rachel Lynn Navarra - DU
- Contributors
- Barry D. Waterhouse (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Other Identifier
- 7158; 991014632827104721