Regulation of GABAergic synaptic transmission in neuronal circuits of the human neocortex

Inhibition has a critical role in information processing in the cerebral cortex by dynamically shaping circuit activity corresponding to the actual behavioural requirements (Kepecs and Fishell 2014). Disinhibition, a selective and transient reduction in synaptic inhibition induced by external stimuli or particular brain states that affect computations in pyramidal neurons, has been proposed to underlie a variety of brain functions, such as the selection of behaviourally relevant stimuli, associative learning and memory expression (Froemke, Merzenich, and Schreiner 2007; Courtin et al. 2014).The function and mechanisms of disinhibition have been much studied in the basal ganglia, where it underlies action selection(Chevalier and Deniau 1990). However, the mechanisms of disinhibition in the cerebral cortex remain to be defined.
The proposed project is likely to yield novel information on principles of organization of neuronal circuits, and define mechanisms of disinhibition in the human cortex. The proposed techniques are plausible and relatively fast, thus the likelihood of achieving the aims is high. On the longer run, the proposed high-resolution dissection of the regulation of inhibition in the human cortex might open new ways of understanding and treating diseases like schizophrenia, autism or attention deficit hyperactivity disorder which have been linked to alterations in GABAergic circuits.