Optogenetic dissection of orbitofrontal to motor cortex circuits for behavioral flexibility
Final Report Abstract
The ability to behave in a flexible manner is an essential skill of humans and animals to survive in a changing environment. Behavioural flexibility requires multiple cognitive processes including recognition of new outcomes to older behaviours, inhibition of the outmoded responses and adaptation of behaviour accordingly. This process is thought to depend on top-down modulation by the prefrontal cortex (PFC) over lower-order circuits. The sub-regions of the prefrontal cortex are differentially involved in the various aspects of behavioural flexibility. Reversal learning and set shifting tasks are similar. The main difference is, in the latter the animals have to shift their attention on one point to a different sensory modality (e.g. from tones to lights). While reversal learning tasks depend on the Orbitofrontal cortex (OFC), set-shifting tasks depend on the medial prefrontal cortex (mPFC). These differences are not well understood and conflicting results for the contribution of PFC-subregions in different aspects of behavioural flexibility are published. We developed a new behavioural task that can dissect flexibility into two of its components: behavioural inhibition and reversal learning. We use optogenetic manipulation techniques in mice, involved in this behavioural flexibility task to manipulate neural activity in neurons within OFC, and ask how inhibition of those cells interferes with impulse control and reversal learning. Our results indicate that OFC inhibition does not influence premature responses/response inhibition but impairs reversal learning. Moreover the LO connects specifically to a secondary anterior lateral motor-cortex area (ALM), that has been associated with learned lick behaviour, previously (Komiyama et al., 2010). We show here, that ALM also influences innate lick-behaviour and hypothesize a role for LO to ALM connections in reversal of a lick-related Go/no Go-task.
Publications
- High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics. Nat Commun. 2018 May 1;9(1):1750
Mager T, Lopez de la Morena D, Senn V, et al.
(See online at https://doi.org/10.1038/s41467-018-04146-3)
