Scientific Understanding of Consciousness
Central Pattern Generator Start-Stop Signals
Nature Volume: 466, Pages: 457–462 (22 July 2010)
Start/stop signals emerge in nigrostriatal circuits during sequence learning
Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Bethesda, Maryland 20892-9412, USA
Learning new action sequences subserves a plethora of different abilities such as escaping a predator, playing the piano, or producing fluent speech. Proper initiation and termination of each action sequence is critical for the organization of behaviour, and is compromised in nigrostriatal disorders like Parkinson’s and Huntington’s diseases. Using a self-paced operant task in which mice learn to perform a particular sequence of actions to obtain an outcome, we found neural activity in nigrostriatal circuits specifically signalling the initiation or the termination of each action sequence. This start/stop activity emerged during sequence learning, was specific for particular actions, and did not reflect interval timing, movement speed or action value. Furthermore, genetically altering the function of striatal circuits disrupted the development of start/stop activity and selectively impaired sequence learning. These results have important implications for understanding the functional organization of actions and the sequence initiation and termination impairments observed in basal ganglia disorders.
Animal behaviour can be organized as sequences of particular actions or movements. The organization of behaviour as sequences of actions is complex and requires the precise timing and ordering of movements within a sequence. It also requires the proper initiation and termination of the sequence; that is, identifying the first and the last elements within the behavioural sequence. Although the study of innate behavioural sequences and fixed action patterns (FAPs) controlled by central pattern generators (CPGs) has received substantial attention, the neural mechanisms underlying the learning and execution of acquired behavioural sequences are still largely unknown. The dorsal striatum and its dopaminergic afferents have been implicated in skill learning and action ‘chunking.’ Importantly, the initiation and termination of sequences of voluntary movements is impaired in disorders affecting the striatum and its dopaminergic inputs, such as Parkinson’s and Huntington’s diseases. Consistently, the learning of new sequences is also compromised in disorders affecting these circuits. Furthermore, neuronal activity in the prefrontal cortex, which projects to the striatum, can change during the signalled initiation and termination of a sequence of saccades. Although previous studies have reported changes in neural activity in the striatum and the substantia nigra pars reticulata (SNr) during the initiation of natural movement sequences, the role of the striatum and of nigrostriatal dopamine in the initiation and termination of newly acquired, self-generated action sequences has not been explored. Here we show that as mice learn to perform a particular behavioural sequence, neural activity specifically signalling the self-paced initiation or termination of the newly acquired sequence emerges in nigrostriatal circuits. In accordance, genetically manipulating the function of these circuits disrupts the development of neural activity signalling sequence initiation or termination and affects sequence learning.
By investigating the behavioural microstructure and correlated neural activity in a self-paced operant task, we found that neurons in nigrostriatal circuits can signal the initiation and termination of self-paced action sequences. This sequence start/stop neural activity emerged as animals learned a specific action sequence, and was specific for particular actions. Importantly, this activity did not reflect interval timing, changes in the inter-press interval during learning, or differences in the expected value during the first or last actions of a sequence. Furthermore, a striatal-specific manipulation that affects plasticity and phasic firing in MSNs impaired the development of start/stop activity in the striatum and selectively disrupted the learning of action sequences without affecting movement speed or the ability to discriminate action value. These data underscore the importance of the basal ganglia in learning and consolidating action sequences, and expand on previous studies showing changes in striatal activity related to the initiation of cue-guided movements, and sequence learning impairments in patients with focal basal ganglia lesions, Parkinson’s and Huntington’s diseases.
Phasic firing of dopaminergic neurons has been widely studied as a reward prediction error signal, and our data confirm that phasic firing of dopaminergic neurons before lever pressing can encode the expected value of the outcome. However, the possible function of phasic dopamine signals in self-paced behaviour, namely in the initiation and termination of specific action sequences, or in the transition between different actions, has been somewhat neglected. Our data show that, in addition to striatal MSNs and SN GABA neurons, the phasic activity of SN DA neurons can signal the initiation and termination of specific action sequences. Hence, although the role of dopamine in motor performance and in Parkinson’s has been mostly associated with tonic dopamine, our findings may have implications for the deficits in initiation and termination of voluntary movement sequences observed in Parkinson’s disease.
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