The effect of norepinephrine release on odor discrimination learning in adult rats

The locus coeruleus is the main source of norepinephrine in the brain with extensive projections to many areas throughout the cortex including the olfactory bulb and piriform cortex. It has been shown that noradrenergic receptor blockade in either olfactory bulb or piriform cortex impairs similar odor discrimination. The goal of this thesis is to test whether enhancing locus coeruleus activity using optogenetic stimulation promotes odor discrimination learning. Adult TH-CRE rats were bilaterally infused with adeno-associated virus containing light-excitable channels targeting noradrenergic locus coeruleus neurons (AAV8- Ef1a-DIO-eChR2 (H134R)-EYFP). In vivo electrophysiology revealed neurons transfected with the viral vector were active when blue light (473 nm) was given at a frequency of 10Hz of 150mA laser current. After confirming the excitability response of the neurons, we tested the effect of light on general locomotor activity. Subsequently, we sought to determine the role of locus coeruleus activation on odor discrimination learning. Food-deprived animals were trained to discriminate between two simple odors, one paired with a food reward. This training was followed by a highly similar odor discrimination in which animals were optogenetically stimulated with a phasic pattern of blue laser light. AAV-ChR2 infused rats discriminated the similar odors after 3 days of training, while non-infused control rats reached the learning criteria in 8 days. The enhanced LC activity induced by photostimulation during highly similar odor discrimination training promoted faster learning

Locus Coeruleus Activation Patterns Differentially Modulate Odor Discrimination Learning and Odor Valence in Rats

The locus coeruleus (LC) produces phasic and tonic firing patterns that are theorized to have distinct functional consequences. However, how different firing modes affect learning and valence encoding of sensory information are unknown. Here, we show bilateral optogenetic activation of rat LC neurons using 10-Hz phasic trains of either 300 ms or 10 s accelerated acquisition of a similar odor discrimination. Similar odor discrimination learning was impaired by noradrenergic blockade in the piriform cortex (PC). However, 10-Hz phasic light-mediated learning facilitation was prevented by a dopaminergic antagonist in the PC, or by ventral tegmental area (VTA) silencing with lidocaine, suggesting a LC–VTA–PC dopamine circuitry involvement. Ten-hertz tonic stimulation did not alter odor discrimination acquisition, and was ineffective in activating VTA DA neurons. For valence encoding, tonic stimulation at 25 Hz induced conditioned odor aversion, whereas 10-Hz phasic stimulations produced an odor preference. Both conditionings were prevented by noradrenergic blockade in the basolateral amygdala (BLA). Cholera Toxin B retro-labeling showed larger engagement of nucleus accumbens-projecting neurons in the BLA with 10-Hz phasic activation, and larger engagement of central amygdala projecting cells with 25-Hz tonic light. These outcomes argue that the LC activation patterns differentially influence both target networks and behavior