Thalamus mediates neocortical Down state transition via GABAB-receptor-targeting interneurons.

Slow-wave sleep is characterized by near-synchronous alternation of active Up states and quiescent Down states in the neocortex. Although the cortex itself can maintain these oscillations, the full expression of Up-Down states requires intact thalamocortical circuits. Sensory thalamic input can drive the cortex into an Up state. Here we show that midline thalamic neurons terminate Up states synchronously across cortical areas. Combining local field potential, single-unit, and patch-clamp recordings in conjunction with optogenetic stimulation and silencing in mice in vivo, we report that thalamic input mediates Down transition via activation of layer 1 neurogliaform inhibitory neurons acting on GABAB receptors. These results strengthen the evidence that thalamocortical interactions are essential for the full expression of slow-wave sleep, show that Down transition is an active process mediated by cortical GABAB receptors, and demonstrate that thalamus synchronizes Down transitions across cortical areas during natural slow-wave sleep.

No friends 1.

Winning entry to the Student Voice 2019. The article focuses on a personal encounter that I had as a medical student when I was sent off to 'study' a patient with a rare disease who had been admitted to hospital.

Partial restoration of physiological UP-state activity by GABA pathway modulation in an acute brain slice model of epilepsy.

In addition to reducing seizures, anti-epileptic treatments should preserve physiological network activity. Here, we used a thalamocortical slice preparation displaying physiological slow oscillations to investigate the effects of anticonvulsant drugs on physiological activity and epileptiform activity in two pharmacological epilepsy models. Thus, we compared the effects of GABA pharmacology on spontaneous physiological and pathological events in slices of the mouse barrel cortex. We show that both reducing inhibition using GABAAR blockers and enhancing excitation by lowering Mg2+ concentration allow for the transition from physiological slow oscillations to epileptiform activity. Our results indicate that GABABR antagonists have pro-convulsive properties by increasing event duration in the low inhibition model and event frequency in the high excitation model. Moreover, we show that GABABR agonists and GABA uptake blockers, known for their anticonvulsant properties, act primarily on epileptiform burst frequency and allow for a partial restoration of physiological events. As a proof of principle, these results indicate that a slice model with spontaneous network events may be a useful pipeline to investigate the effects of anti-epileptic drugs on both epileptiform and physiological network activity.