Cholinergic Modulation of Parvalbumin Neurons in Attention
Abstract
The lack of treatments targeting the cognitive symptoms of schizophrenia has prompted interest in understanding the neural mechanisms of attention in the context of the disease. Acetylcholine (ACh) and parvalbumin-expressing interneurons (PVIs) are pivotal in controlling top-down attention in the prefrontal cortex, with their dysfunction linked to schizophrenia. Despite evidence hinting at ACh's interaction with PVIs during attention, no prior studies have explored this interaction and its role in attention. This thesis employed pharmacological inhibition of muscarinic and nicotinic ACh receptors, alongside in vivo calcium recordings from prefrontal PVIs in mice engaged in an attention-based task. Muscarinic inhibition impaired behavior and PVI activity. M1-muscarinic receptor inhibition had no effect, while prefrontal nicotinic inhibition did not alter behavior or PVI activity. This indicates that prefrontal muscarinic signalling modulates PVI activity and plays a significant role in attention, while prefrontal nicotinic signalling lacks impact on prefrontal PVIs or a substantial role in attention.