denotes equal contribution; Correspondence and requests for materials should be addressed to celikel@neurophysiology.nl Magnetic neuromodulation has outstanding promise for the development of novel neural interfaces without direct physical intervention with the brain. Here we tested the utility of Magneto in the adult somatosensory cortex by performing whole-cell intracellular recordings in vitro and extracellular recordings in freely moving mice. Results show that magnetic stimulation does not alter subthreshold membrane excitability or contribute to the generation of action potentials in virally transduced neurons expressing Magneto. Recently introduced Magneto (Wheeler et al., 2016) might provide the highly sought after neuromagnetic actuation in a cell-targeted manner. Some of the excitement about Magneto originates from its design which is comprised of a calcium-permeable non-selective cation channel (Transient receptor potential cation channel subfamily V member 4, TRPV4) fused to the paramagnetic protein ferritin (Wheeler et al., 2016) . This single-construct approach provides a simplified mean for magnetic intervention with neuronal activity.Here, we used lentiviral delivery of Magneto linked to mCherry (Magneto2.0-P2A-mCherry), expressed under the control of ubiquitin promoter for >2 weeks (Fig.1a) before observing and interfering with neural activity (see Methods online), and after confirming successful cleavage of Magneto from mCherry (Suppl. Fig.2a-3) and the subcellular analysis of the expressed protein localization (Suppl. Fig.2b) in a neuronal cell line . Chronic extracellular recordings in freely moving mice (Allen et al., 2003;Celikel et al., 2004;Clem et al., 2008) with 15 tetrodes enabled high-density sampling of neural activity in the vicinity of transduced cells, and yielded well-isolated (Suppl. Fig.4) , stable units (Fig.1b) . Comparison of firing rates within cells across magnetic stimulus conditions (off vs on) showed that magnetic stimulation does not alter the rate of action potentials (APs; Fig.1c ); neither does it modulate the inter-spike interval within cells, nor spike-timing across single units recorded from the same tetrode (Suppl. Fig.5,6) . The lack of spiking was not because neurons could not
Magnetic neuromodulation has outstanding promise for the development of novel neural interfaces without direct physical intervention with the brain. Here we tested the utility of Magneto in the adult somatosensory cortex by performing whole-cell intracellular recordings in vitro and extracellular recordings in freely moving mice. Results show that magnetic stimulation does not alter subthreshold membrane excitability or contribute to the generation of action potentials in virally transduced neurons expressing Magneto.Recently introduced Magneto (Wheeler et al., 2016) might provide the highly sought after neuromagnetic actuation in a cell-targeted manner. Some of the excitement about Magneto originates from its design which is comprised of a calcium-permeable non-selective cation channel (Transient receptor potential cation channel subfamily V member 4, TRPV4) fused to the paramagnetic protein ferritin (Wheeler et al., 2016) . This single-construct approach provides a simplified mean for magnetic intervention with neuronal activity.Here, we used lentiviral delivery of Magneto linked to mCherry (Magneto2.0-P2A-mCherry), expressed under the control of ubiquitin promoter for >2 weeks (Fig. 1a) before observing and interfering with neural activity (see Methods online), and after confirming successful cleavage of Magneto from mCherry (Suppl.Fig. 2a-3) and the subcellular analysis of the expressed protein localization (Suppl.Fig. 2b) in a neuronal cell line . Chronic extracellular recordings in freely moving mice (Allen et al., 2003; Celikel et al., 2004; Clem et al., 2008) with 15 tetrodes enabled high-density sampling of neural activity in the vicinity of transduced cells, and yielded well-isolated (Suppl.Fig. 4) , stable units (Fig. 1b) . Comparison of firing rates within cells across magnetic stimulus conditions (off vs on) showed that magnetic stimulation does not alter the rate of action potentials (APs; Fig. 1c ); neither does it modulate the inter-spike interval within cells, nor spike-timing across single units recorded from the same tetrode (Suppl.Fig. 5,6) . The lack of spiking was not because neurons could not 1
Background: The recent release of two large intracellular electrophysiological databases now allows high-dimensional systematic analysis of mechanisms of information processing in the neocortex. Here, to complement these efforts, we introduce a freely and publicly available database that provides a comparative insight into the role of various neuromodulatory transmitters in controlling neural information processing. Findings: A database of in vitro whole-cell patch-clamp recordings from primary somatosensory and motor cortices (layers 2/3) of the adult mice (2-15 months old) from both sexes is introduced. A total of 464 current-clamp experiments from identified excitatory and inhibitory neurons are provided. Experiments include recordings with (i) Step-and-Hold protocol during which the current was transiently held at 10 steps, gradually increasing in amplitude, (ii) 'Frozen Noise' injections that model the amplitude and time-varying nature of synaptic inputs to a neuron in biological networks. All experiments follow a within neuron across drug design which includes a vehicle control and a modulation of one of the following targets in the same neuron: dopamine and its receptors D1R, D2R, serotonin 5HT1f receptor, norepinephrine Alpha1, and acetylcholine M1 receptors. Conclusions: This dataset is the first to provide a systematic and comparative insight into the role of the selected neuromodulators in controlling cellular excitability. The data will help to mechanistically address how bottom-up information processing can be modulated, providing a reference for studying neural coding characteristics and revealing the contribution of neuromodulation to information processing.
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