Blue Brain is delighted to announce that the next seminar in the series in Neural Computation, will be on ‘Cell-specific cholinergic modulation of neocortical neurons’. The seminar will be given by Dirk Feldmeyer, Professor, University Hospital Medical School Aachen, and Professor and Group Leader, Research Centre Jülich.
Acetylcholine (ACh) is a potent neuromodulator in the brain and is in the neocortex mainly released from afferents of the basal forebrain. The effects of ACh are mediated by both G-protein coupled receptors and ligand-gated ion channels termed muscarinic and nicotinic ACh receptors (mAChRs and nAChRs). While nAChR activation leads exclusively to an enhancement of neuronal firing and synaptic transmission, mAChR can inhibit or activate neurons depending on the specific receptor subtype expression.
Using the primary somatosensory barrel cortex as a model system I will present data on how neuronal activity is modulated by the interaction of different types of mAChR subtype but also nAChRs. I will demonstrate that in the different cortical layers ACh can show exclusively excitatory, exclusively inhibitory and a combination of both effects, depending on the neuron type and its axonal projection pattern. In addition, I will also describe how both mAChRs and nAChRs affect the synaptic release probability and how this compares to its effects on neuronal excitability. Our finding support the hypothesis that mAChR effects are mediated already at low extracellular concentration (1-10 µM) while nAChRs are generally activated at significantly higher concentrations (> 100 µM). This is consistent with the view that activation of mAChRs occurs either via volume release of the transmitter or spill-over from cholinergic synapses. In contrast, nAChRs are mainly activated by direct synaptic release; however, some presynaptic nAChRs may also be activated via spill-over. Thus, the action of ACh in the neocortex is complex, highly neuron-specific, and depends on the type of synaptic connection.
For further information, please visit the EPFL website.