Jean-Philippe Dufour

In classical Pavlovian conditioning, it is well-established that midbrain dopamine neurons respond to conditioned stimuli (CS) that predict a reward. However, how the dopamine neurons associate a neutral CS to a reward remains unknown. Here, we show that in male rats and in both male and female mice, the superior colliculus (SC) develops neuronal responses to a visual CS during conditioning, which in turn drive the responses of dopamine neurons. Visual responses in the SC were only potentiated when a behaviorally meaningful time interval separated the visual stimulus and reward. Potentiation also required the convergence of visual, dopamine and serotonin inputs to the SC. Importantly, blocking potentiation of the visual response was sufficient to suppress the dopamine responses following a CS. These results reveal a mechanism for how the brain forms associations between unconditioned stimuli and behaviorally meaningful visual information during classical conditioning.

Background/Objectives: Haemodynamic changes following ischaemic large-vessel occlusion (LVO) stroke might affect clinical outcome, including after endovascular recanalization. Using non-invasive quantitative MRA (qMRA), we report for the first time serial intracranial flow rate measurements following LVO and investigate flow rate changes, collateral pathway development, and their possible clinical significance. Methods: We report data from the prospective IMPreST study (Interplay of Microcirculation and Plasticity after Ischemic Stroke, registered at clinicaltrials.gov, no. NCT04035746). Patients with first-ever unilateral internal carotid artery (ICA) and/or M1/2 middle cerebral artery (MCA) occlusions were included. After being evaluated for gold-standard treatment, including endovascular thrombectomy, patients underwent early (p = 0.016), possibly reflecting subacute activation of leptomeningeal collaterals via P2-PCA. In recanalized patients, lower M1 VFR ratios at 7 ± 3 days were significantly associated with a higher NIHSS at discharge after adjusting for infarct size, age, and NIHSS at admission (p = 0.02). Total hemispheric flow significantly decreased by up to 9% between early and late measurements in both the ischaemic and non-ischaemic hemispheres (p = 0.005). Conclusions: qMRA may help to understand flow status and collateral pathway activation after LVO stroke. Past the acute phase, low arterial flow to the affected region is associated with poorer neurological status, including after successful recanalization.

Here, we characterized the dynamics of sleep spindles, focusing on their damping, which we estimated using a metric called oscillatory-Quality (o-Quality), derived by fitting an autoregressive model to electrophysiological signals, recorded from the cortex in mice. The o-Quality of sleep spindles correlates weakly with their amplitude, shows marked laminar differences and regional topography across cortical regions, reflects the level of synchrony within and between cortical networks, is strongly modulated by sleep-wake history, reflects the degree of sensory disconnection, and correlates with the strength of coupling between spindles and slow waves. As most spindle events are highly localized and not detectable with conventional low-density recording approaches, o-Quality thus emerges as a valuable metric that allows us to infer the spread and dynamics of spindle activity across the brain and directly links their spatiotemporal dynamics with local and global regulation of brain states, sleep regulation, and function.