Beierlein, M. | bioRxiv Science

bioRxiv2018

Synaptic release of acetylcholine rapidly suppresses cortical activity by recruiting muscarinic receptors in layer 4

Basal forebrain (BF) cholinergic projections to neocortex dynamically regulate information processing. However, the underlying synaptic and cellular mechanisms remain poorly understood. While synaptically released acetylcholine (ACh) can recruit nicotinic ACh receptors (nAChRs) expressed in distinct types of interneurons, previous work has not defined a clear role for muscarinic ACh receptors (mAChRs) in the fast cholinergic control of cortical activity. To address this question, we employed a slice model of cortical activity and used optogenetics to selectively activate cholinergic afferents. We found that transient ACh increases led to a rapid and persistent suppression of cortical activity, mediated by mAChRs in layer 4 and by nAChRs in layer 2/3. Furthermore, mAChR-dependent cholinergic control was mediated at least in part by a short-latency and long-lasting inhibition of layer 4 excitatory neurons. Thus, the activation of postsynaptic mAChRs is central to the flexible cholinergic control of cortical activity.

neuroscience↗

bioRxiv2017

Fluidic Microactuation of Flexible Electrodes for Neural Recording

Ultra-flexible microelectrodes that can bend and flex with the natural movement of the brain reduce the inflammatory response and improve the stability of long-term neural recordings.1-5 However, current methods to implant these highly flexible electrodes rely on temporary stiffening agents that increase the electrode size6-10 thus aggravating neural damage during implantation, which leads to cell loss and glial activation that persists even after the stiffening agents are removed or dissolve.11-13 A method to deliver thin, ultra-flexible electrodes deep into neural tissue without increasing the stiffness or size of the electrodes will enable minimally invasive electrical recordings from within the brain. Here we show that specially designed microfluidic devices can apply a tension force to ultra-flexible electrodes that prevents buckling without increasing the thickness or stiffness of the electrode during implantation. Additionally, these \"fluidic microdrives\" allow us to precisely actuate the electrode position with micron-scale accuracy. To demonstrate the efficacy of our fluidic microdrives, we used them to actuate highly flexible carbon nanotube fiber (CNTf) microelectrodes11,14 for electrophysiology. We used this approach in three proof-of-concept experiments. First, we recorded compound action potentials in a soft model organism, the small cnidarian Hydra. Second, we targeted electrodes precisely to the thalamic reticular nucleus in brain slices and recorded spontaneous and optogenetically-evoked extracellular action potentials. Finally, we inserted electrodes more than 4 mm deep into the brain of rats and detected spontaneous individual unit activity in both cortical and subcortical regions. Compared to syringe injection, fluidic microdrives do not penetrate the brain and prevent changes in intracranial pressure by diverting fluid away from the injection site during insertion and actuation. Overall, the fluidic microdrive technology provides a robust new method to implant and actuate ultra-flexible neural electrodes.

neuroscience↗