Since the start of the project, we have completed five studies currently in various stages of publication, and that are posted to the pre-print server BioRxiv. First, by analyzing phasic dopamine activity in relation to decision-making behavior and computational reinforcement learning models, we discovered that mice use efficient, compressed representations of cognitive variables to perform the task, extending the principle of efficient coding to the cognitive domain.
Second, by combining fiber photometric recordings of activity from the projection cell types initiating the two major circuits of the basal ganglia, so called direct and indirect medium spiny neurons of the striatum (dMSN, iMSN) with a series of optogenetic inhibition experiments in the context of the aforementioned behavioral task, we have revealed a novel model of sensorimotor striatum wherein the direct pathway appears to be necessary for augmenting generalized movement vigor, and the indirect pathway for the proactive suppression of specific behaviors. These data reveal new insight into the etiology of neurological and neuropsychiatric diseases such as Parkinson’s, Huntington’s diseases, and ADHD that are characterized by varying degrees of dysfunction in suppressive control of behavior.
Third, we applied an unconventional manipulation, temperature, to striatal tissue to rescale striatal activity in time, and found we could rescale temporal decisions. In contrast, temperature did not affect low level timing of movements. These data demonstrate that the time-course of evolving striatal population activity dictates the speed of a latent timing process that is used to guide decision-making but that is not used to specify the details of movement execution, with broad implications for understanding both the neural basis of timing and, more generally, the role of basal ganglia circuits in behavior.
Fourth, we applied the principles of temporal scaling to an existing data set wherein stimulus magnitude was shown to alter the temporal judgments of rats, and discovered a tight link between the effects of stimulus magnitude on duration judgment and temporal scaling of neuronal activity.
Lastly, we developed new computational reinforcement learning theory to extend the concept of distributional reward coding to multiple dimensions, both time and magnitude, and discovered evidence that computations similar to that predicted by the theory are implemented in the brain by recording from optogenetically tagged midbrain dopamine neurons in mice.
All of this work has been communicated at scientific meetings including the annual Cosyne conferences, the, Society for Neuroscience meetings, the Ascona conference on neural circuits, a Janelia Farm workshop on foraging, a Brain prize meeting on neural dynamics, as well as many invited seminars spanning North and South America and Europe. It has also been discussed and written about extensively in both the national Portuguese media and Internationally, as well as on social media.
