The role of norepinephrine in learning: Cerebellar motor learning in rats

Delay classical eyeblink conditioning is an important model of associative, cerebellar dependent learning. Norepinephrine (NE) plays a significant modulatory role in the acquisition of learning; other neurotransmitter systems are also at play. The goal of this dissertation was to determine whether NE, GABA and glutamate (Glu) release is observed in cerebellar cortex during delay eye blink conditioning, and whether such release was selectively associated with training and not due only to stimulatory sensory input. The data support the hypothesis of noradrenergic and GABAergic system involvement in motor learning with NE as a modulator of early responding and GABA as a mediator of the learned response. In addition to neurotransmitter levels, we found that the local administration into the cerebellum of Rp-cAMP and propranolol impair the consolidation of learning when administered post training on the eyeblink conditioning task indicating that the B-adrenergic receptor and the cAMP downstream signaling cascade are essential for memory consolidation. These results support the hypothesis of NE acting as a neuromodulator in the cerebellum for the acquisition of motor learning. A similar experimental design was applied to aged animals and the neurochemical pattern of release was haracterized by a delay in the response to eyeblink conditioning and smaller amounts of the neurotransmitter evoked by the paired US-CS. It is hypothesized that the impairment in aging could be due to excitotoxicity caused by chronic inflammation. The present study also approached this issue by targeting the pro-inflammatory cytokine TNF-a and we found that suppression of TNF-a in aged animals improved learning