Reward-based learning through layer-specific cortical optogenetic stimulation in mice

Abstract

In our everyday lives, we perform multiple sensorimotor transformations, where a particular sensory stimulus triggers an appropriate motor response. A well-studied task for investigating sensorimotor transformations involves training water-restricted mice to lick for a water reward in response to a brief whisker stimulus. Evidence suggests that the whisker primary somatosensory cortex (wS1) contributes significantly to detecting the whisker stimulus in this task. The wS1 is organised into 6 layers, with neurons in Layer 4 (L4) receiving major sensory inputs from the brainstem and the thalamus. The sensory information then rapidly spreads to Layers 2/3 (L2/3), 5 (L5), and 6, which project to many cortical and subcortical structures, leading to a motor command. However, the neuronal population(s) in wS1 that play a critical role in driving goal-directed licking during this detection task remain unknown. We trained mice (expressing an excitatory opsin) from 4 layer-specific (L2/3, L4, L5 IT(Intratelencephalic) and L5-PT(Pyramidal tract)) Cre lines to lick in response to an optogenetic stimulus instead of a whisker stimulus. L4, L5-IT and L5-PT mice were able to respond to the optogenetic stimulus quickly (1st day) while L2/3 mice only responded on the 3rd day. When compared across layers, L4 and L5-IT mice showed a stronger response than L2/3 and L5-PT. L5-IT excitatory neurons may prove to be suitable for further investigation in this transformation due to their known projections to the striatal projection neurons in the dorsolateral striatum (some of which evoke licking). Overall, this project sheds light on the relative strength of the different layers of the wS1 in driving goal-directed licking and thus provides a basis for more focused investigations of critical subpopulations in the wS1 that facilitate sensorimotor transformations during the detection task.