Encoding behavioural sequences: a possible role for striatal neuropeptides

The neuropeptides substance P and enkephalin are abundant in the striatum, the largest input structure of the basal ganglia. Although the basal ganglia are thought to play a significant role in action selection, the role of substance P and enkephalin in striatal processing is unknown, although recent computational work suggests they may be involved in action sequence performance and acquisition. Hence, the focus of the present thesis was on testing how blocking substance P and enkephalin’s main receptors affected both innate and learned behavioural sequences. The lack of specialized techniques directed at finding sequential and temporal patterns when analysing the roles of these two neuropeptides encouraged the use of Markov analyses to identify grooming and locomotion sequences in an open field experiment. Emphasis was placed on evaluating the effect of blocking substance P and enkephalin's receptors on the grooming chain, a naturally fixed innate pattern displayed by rats. Furthermore, by using temporal pattern techniques, we were able to discern the effects on temporal aspects of sequencing. This first study suggested that substance P could be important for regulating transitions between behaviours, whereas enkephalin’s role could be more related to timing aspects. The second experiment extended the analysis beyond innate and spontaneous behavioural patterns to learning, in which again the role of substance P and enkephalin have not been thoroughly investigated. Thus, experiments were conducted to analyse the effects of blocking substance P and enkephalin's receptors on learning and performing a crystallised action sequence. The results identified substance P as a key neuromodulator in learning new action sequences. Finally, to try to get a more mechanistic understanding of the role of substance P in sequence learning, a reinforcement learning model was developed which allowed the in silico replication of the experimental task performed in the previous study and the testing of several biologically constrained hypothesis about the role of substance P. This last study suggested that SP could be playing a key role in the maintenance of a sequence representation when contingencies change, giving it a possible role to break “super habits” such as those present in addictions.