Functional roles of midbrain dopamine neurons in associative learning

These experiments examine the functional properties of midbrain dopamine neurons during conditioned learning tasks designed to test their responses to sensory events. Dopamine neurons are predominately located within two regions of the midbrain, the substantia nigra pars compacta and the ventral tegmental area. This study aims to examine the function of dopamine neurons located in the substantia nigra pars compacta, the region most densely packed with dopamine neurons and known to receive short-latency visual information from the superior colliculus. Dopamine signaling is thought to play a critical role in reward-related learning, and the predominant hypothesis proposes that dopamine neurons signal the expected reward values of sensory stimuli in the form of a short-latency phasic burst. Thus, the reward prediction hypothesis assumes that information relevant to determining stimulus identity informs dopamine neuron firing. Recently, this critical assumption has been questioned and given rise to an alternative hypothetical framework proposing that dopamine activity represents a more generic signal of stimulus salience. Proponents of this competing hypothesis note that the requisite feature-based discrimination would not be possible in a period short enough to inform the dopamine response. Instead, the "saliency hypothesis" proposes that short-latency dopamine activity reflects the relative salience of stimuli (independent of their reward value) and that this signal likely derives from the superior colliculus (SC), a subcortical structure lacking the capacity for fine feature discrimination but specializes in detecting and locating salient sensory events. Support for this latter view comes from recent anatomical evidence for a projection from the SC to substantia nigra pars compacta and physiological findings showing that SC activity can drive phasic dopamine activity. This dissertation provides a critical test of these competing hypotheses through in vivo recording from dopamine neurons in the context of behavioral tasks capable of dissociating activity relating to stimulus salience from that which predicts reward value. Results from these studies reveal a biphasic neural response and suggest that dopamine neurons both encode the occurrence of salient events and predict reward at distinct temporal latencies.