Using chemogenetics to re-adjust the output of the basal forebrain after cholinergic neuron depletion;

Dementia due to the ageing world population is amongst the most defining public health concerns of this century. According to the world-health-organization, the incidence rate of neurodegenerative diseases such as Alzheimer's Disease (AD) is expected to rise exponentially in the coming decades. In addition to the decline in quality of life for the patients, the economic and societal burden of these conditions is huge. The recent failure of numerous clinical trials in AD calls for ideas in the direction of novel treatment strategies. To this end, the importance of targeted reduced systems such as animal models remains irreplaceable. In this project we will pursue a novel hypothesis that depletion of cholinergic neurons in the basal forebrain results to long-lasting changes in the GABAergic output of this neuromodulatory system and contributes to disease progression. We will first combine resting state fMRI with calcium imaging to associate both whole-brain BOLD-signal and functional connectivity with their direct underlying neuronal correlates in a rat model of cholinergic depletion and then use designer receptors activated exclusively by designer drugs (DREADDs) in the basal forebrain in order to re-adjust the output to the cerebral cortex and hippocampus. Last but not least we will evaluate the behavioral improvements caused by this manipulation.

Keywords:OPTICAL IMAGING, OPTOGENETICS, FUNCTIONAL IMAGING

Disciplines:Behavioural neuroscience, Cognitive neuroscience, Neuroanatomy, Neurophysiology, Neuroimaging