Correlations in neuromodulatory codes during different learning processes

Neuromodulatory systems often regulate seemingly overlapping cognitive processes and show similar modes of action. To reveal possible synergistic or antagonistic relations and to better understand the exact role of these systems, in a comprehensive series of experiments, we simultaneously monitored pairs of neuromodulatory systems in mice performing a series of behavioral tasks focusing on different aspects and mechanisms of learning, such as psychometric operant learning and implicit statistical learning. In the examined subcortical target areas (the ventral striatum and the basolateral amygdala), we observed robust, rapid, strongly correlated but not synchronous event-related release of dopamine and acetylcholine, linked to behavioral feedback and outcome predictions in all tasks, which closely resembled the spiking activity of their deep brain neuronal source (the ventral tegmental area and the diagonal band of Broca, respectively). On the other hand, other neuromodulators (serotonin and noradrenalin) and neuromodulator release in the prefrontal cortex in general, were more characterized by a slower oscillatory alteration, yet also in a task-dependent manner, entrained by behaviorally salient events. Our results indicate that multiple modes of learning rely on a precisely coordinated release of various neuromodulators, which act on a somewhat heterogeneous manner across different brain areas.