Dr. Poulet (D) & Prof. Brecht (D)
Dr. James F.A.
Prof. Dr. Michael
Max-Delbrück-Centrum für Molekulare Medizin
Neurowissenschaftliches Forschungszentrum Berlin
Over the last years, the applicants have been making single and dual whole-cell patch clamp recordings of cortical neurons in awake, behaving mice and rats. We have observed prominent changes in brain state closely correlated with changes in behaviour. Nearby neurons shown highly correlated patterns of synaptic, spontaneous activity when the animal is sitting quietly, but during behaviour there is a strong reduction in correlation, increasing the overall coding capacity of the neocortex. We have preliminary evidence to suggest acetylcholine (ACh) is involved in regulating cortical processing and may also have a strong impact on sensory processing and behaviour. Here we will use state of the art neuronal recording and stimulating techniques to investigate the precise role of ACh in cortical processing in awake, behaving mice.
We will combine whole-cell recordings and intracellular stainings of excitatory pyramidal neurons in the awake mouse primary somatosensory cortex with specific stimulation of cortically-projecting cholinergic neurons in the basal forebrain. To target stimulation to cholinergic neurons we will inject viral vectors to express the blue light sensitive cation channel channelrhodospin-2 (ChR2) in cholinergic neurons in the basal forebrain. We will stimulate ChR2 expressing ACh neurons using an optic fibre coupled to a blue laser. Optical stimulation will be combined with sensory tactile stimulation and whole-cell recordings in awake mice to examine the effect of ACh on cortical synaptic dynamics and sensory processing. We will go on to train mice to perform a sensory detection task and investigate the role of ACh on learning and sensory perception. Our in vivo approach will be complemented with two in vitro collaborations using ChR2-ACh axon fibre stimulation in a brain slices to investigate the impact of ACh on synaptic processing and cortical oscillations. Finally, we will combine electrophysiological recordings and ChR2 stimulation with population calcium imaging of cortical neurons.