<p dir="ltr">The ability to selectively respond to a desirable stimulus while ignoring the surroundings is essential for efficient decision making, such as sensing food amongst rocks. This requires accurate discrimination of the input features and their associated values. Current understanding of value-modulated sensory processing is highly biased towards the visual modality, and little is known about how tactile signals evolve across cortical and subcortical regions in the same goal directed task. It is also unclear whether task engagement and action outcome modulates neural representation of the sensory and value space.</p><p dir="ltr">To answer these questions, we investigated the mouse primary somatosensory cortex (S1) and the superior colliculus (SC) while the animal was performing an active spatial discrimination task. The mice were trained to actively touch and associate a whisker-dependent stimulus with reward (GO whisker) while ignoring tactile input to the adjacent whisker (NoGo whisker). We hypothesize that sensory information in the S1 neocortex is encoded in the form of physical features such as location, which is then converted into a map of stimulus value in the SC. We found that both S1 and SC neurons accurately discriminated between adjacent whisker stimuli with the SC displaying a much stronger preference than S1 for the higher valued stimulus. This bias was unique to SC wherein spiking activities were facilitated for the rewarded stimulus and suppressed for the negative stimulus. Importantly, removing the opportunity for positive stimulus selection reduced but did not abolish positive bias in the SC, reinforcing its role in value-based sensory modulation. Moreover, the spontaneous activity in SC but not S1 predicted response latency and performance accuracy. Taken together, this study demonstrated a transformation of stimulus priority from a somatotopic map in S1 to a value map in SC.</p>

One of the most common risk factors for stroke is diabetes. Diabetics are 2 to 4 times more likely to have a stroke and are also significantly more likely to show poor functional recovery. In order to determine why diabetes is associated with poor stroke recovery, we tested the hypotheses that diabetes either exacerbates initial stroke damage, or inhibits neuronal circuit plasticity in surviving brain regions that is crucial for successful recovery. Type 1 diabetes was chemically induced in mice four weeks before receiving a targeted photothrombotic stroke in the right forelimb somatosensory cortex to model a chronic diabetic condition. Following stroke, a subset of diabetic mice were treated with insulin to determine if controlling blood glucose levels could improve stroke recovery. Consistent with previous studies, one behavioural test revealed a progressive improvement in sensory function of the forepaw in non-diabetic mice after stroke. By contrast, diabetic mice treated with and without insulin showed persistent deficits in sensori-motor forepaw function. To determine whether these different patterns of stroke recovery correlated with changes in functional brain activation, forepaw evoked responses in the somatosensory cortex were imaged using voltage sensitive dyes at 1 and 14 weeks after stroke. In both diabetic and non-diabetic mice that did not have a stroke, brief mechanical stimulation of the forepaw evoked a robust and near simultaneous depolarization in the primary (FLS1) and secondary somatosensory (FLS2) cortex. One week after stroke, forepaw-evoked responses had not been remapped in the peri-infarct cortex in both diabetic and non-diabetic mice. Fourteen weeks after stroke, forepaw evoked responses in non-diabetic mice re-emerged in the peri-infarct cortex whereas diabetic mice showed very little activation, reminiscent of the 1 week recovery group. Moreover, controlling hyperglycemia using insulin therapy failed to restore sensory evoked responses in the peri-infarct cortex. In addition to these differences in peri-infarct responsiveness, we discovered that stroke was associated with increased responsiveness in FLS2 of non-diabetic, but not diabetic or insulin treated mice. To determine the importance of FLS2 in stroke recovery, we silenced the FLS2 cortex and found that it re-instated behavioural impairments in stroke recovered mice, significantly more so than naïve mice that still had a functioning FLS1. Collectively, these results indicate that both diabetes and the secondary somatosensory cortex play an important role in determining the extent of functional recovery after ischemic cortical stroke. Furthermore, the fact that insulin therapy after stroke did not normalize functional recovery, suggests that prolonged hyperglycemia (before stroke) may induce pathological changes in the brain’s circulation or nervous system that cannot be easily reversed. / Graduate