Modulation of Giant Depolarizing Potentials (GDPs) in Human Large Basket Cells by Norepinephrine and Acetylcholine

Abstract

AbstractRhythmic brain activity has been implicated in many brain functions and it is sensible to neuromodulation, but so far very few studies have investigated this activity on the cellular levelin vitroin human tissue samples. In this study we revealed and characterized a novel rhythmic network activity in human neocortex. Intracellular patch-clamp recordings showed that giant depolarizing potentials (GDPs) were frequently found in human cortical neurons. GDPs appeared in a low frequency band (∼ 0.3 Hz) similar to that described for slow oscillationsin vivoand displayed large amplitudes and long decay times. Under the same experimental conditions, no rhythmic activity was found in L2/3 of the rat neocortex. GDPs were predominantly observed in a subset of L2/3 interneurons considered to be large basket cells based on previously described morphological features. In addition, GDPs are highly sensitive to norepinephrine (NE) and acetylcholine (ACh), two neuromodulators known to modulate low frequency oscillations. NE increased the frequency of the GDPs by enhancing β-adrenergic receptor activity while ACh decreased GDP frequency through M4muscarinic receptor-activation. Multi-electrode array (MEA) recordings demonstrated that NE promoted synchronous oscillatory network activity while the application of ACh led to a desynchronization of neuronal activity. Our data indicate that the human neocortex is more prone to generate slow wave activity, which was reflected by more pronounced GDPs in L2/3 large basket cells. The distinct modulation of GDPs and slow wave activity by NE and ACh exerts a specific modulatory control over the human neocortex.