Final Report Summary - BRAINSIGNALS (Optical dissection of circuits underlying fast cholinergic signalling during cognitive behaviour)
More than one-third of all people are estimated to experience mild to severe cognitive impairment as they age. Acetylcholine (ACh) levels in the brain diminish with aging, and nicotinic ACh receptor (nAChR) stimulation is known to enhance cognitive performance. The prefrontal cortex (PFC) is involved in a range of cognitive functions and is thought to mediate attentional focus. How ACh controls the prefrontal cortex neuronal circuitry to support attention is poorly understood. In this ERC-funded project, we have uncovered neuronal mechanisms by which ACh modulates different types of neurons and their synaptic connections in the medial prefrontal cortex. By selective activation with optogenetics, we have identified how cholinergic inputs activate nicotinic ACh receptors distributed throughout different layers of the prefrontal cortex through fast synapses. In addition, we have determined how different subdivisions of the medial prefrontal cortex are involved in attention behavior on timescales relevant for cognitive behavior. Furthermore, we determined how different sources of ACh in the brain are involved in controlling attention behavior. Finally, we have shown that the neuronal mechanisms involved in cholinergic modulation of neocortical circuits are well-conserved from mouse to man.