Fast and slow transitions in frontal ensemble activity during flexible sensorimotor behavior

Abstract

The ability to shift between repetitive and goal-directed actions is a hallmark of cognitive control. Previous studies have reported that adaptive shifts in behavior are accompanied by changes of neural activity in frontal cortex. However, neural and behavioral adaptations can occur at multiple time scales, and their relationship remains poorly defined. Here, we developed a novel adaptive sensorimotor decision-making task for head-fixed mice, requiring them to shift flexibly between multiple auditory-motor mappings. Two-photon calcium imaging of secondary motor cortex (M2) revealed different ensemble activity states for each mapping. Notably, when adapting to a conditional mapping, transitions in ensemble activity were abrupt and occurred before the recovery of behavioral performance. By contrast, gradual and delayed transitions accompanied shifts towards repetitive responding. These results demonstrate distinct ensemble signatures associated with the start versus end of sensory-guided behavior, and suggest that M2 leads in engaging goal-directed response strategies that require sensorimotor associations.

Secondary Motor Cortex: Where ‘Sensory’ Meets ‘Motor’ in the Rodent Frontal Cortex

“…Furthermore, deficits in cue-guided actions are more pronounced during moments of behavioral flexibility, when animals have to learn or adapt. Siniscalchi et al trained head-fixed mice to switch multiple times between multiple non-spatial auditory-motor mappings during a single session [44]. In agreement with sensorimotor deficits, M2-inactivated animals made more perseverative errors when adjusting to perform sound-guided actions.…”

“…Moving forward, it will be useful to specify the domains of antecedent conditions most dependent on a functional M2. So far, some conditions engage M2 (visual-non spatial [43], auditory click train comparison [42], auditory click train plus a delay period [54], auditory frequency-modulated sweeps [44], prior action [46]), whereas others do not (visual-spatial [42], auditory click train [55]). Do more complex and non-spatial sensory stimuli involve sensory cortices, and thus invoke the use of M2?…”

“…Such early choice-related activity in M2 has trial-to-trial variations matching those of the upcoming response, suggesting that it contributes causally to action planning [54]. Some cells prefer contralateral choices, whereas others neurons are more active for ipsilateral choices [44,54]. What is the significance of having the earliest choice-related activity in the entire frontal-striatal network?…”

“…3A) [44]. Notably, M2 neurons exhibited distinct activity patterns, both at the single-cell and ensemble levels, for cue-guided versus non-conditional trials (Figs.…”

Learning in the Rodent Motor Cortex

“…Likewise, the relationship between activity of the motor thalamus and movement and how it may change with learning are largely unknown (Goldberg et al 2013, Sommer 2003). Another generally uncharacterized manner of control comes from frontal cortical areas, which have privileged, direct access to the deep layers of motor cortex (Hooks et al 2013) and may be important for cognitive control of movement (Siniscalchi et al 2016). …”