What any sensory neuron knows about the world is one of the cardinal questions in Neuroscience. Information from the sensory periphery travels across synaptically coupled neurons as each neuron encodes information by varying the rate and timing of its action potentials (spikes). Spatiotemporally correlated changes in this spiking regimen across neuronal populations are the neural basis of sensory representations. In the somatosensory cortex, however, spiking of individual (or pairs of) cortical neurons is only minimally informative about the world. Recent studies showed that one solution neurons implement to counteract this information loss is adapting their rate of information transfer to the ongoing synaptic activity by changing the membrane potential at which spike is generated. Here we first introduce the principles of information flow from the sensory periphery to the primary sensory cortex in a model sensory (whisker) system, and subsequently discuss how the adaptive spike threshold gates the intracellular information transfer from the somatic post-synaptic potential to action potentials, controlling the information content of communication across somatosensory cortical neurons.

Background Neurons in the supragranular layers of the somatosensory cortex integrate sensory (bottom-up) and cognitive/perceptual (top-down) information as they orchestrate communication across cortical columns. It has been inferred, based on intracellular recordings from juvenile animals, that supragranular neurons are electrically mature by the fourth postnatal week. However, the dynamics of the neuronal integration in adulthood is largely unknown. Electrophysiological characterization of the active properties of these neurons throughout adulthood will help to address the biophysical and computational principles of the neuronal integration. Findings Here, we provide a database of whole-cell intracellular recordings from 315 neurons located in the supragranular layers (L2/3) of the primary somatosensory cortex in adult mice (9–45 weeks old) from both sexes (females, N = 195; males, N = 120). Data include 361 somatic current-clamp (CC) and 476 voltage-clamp (VC) experiments, recorded using a step-and-hold protocol (CC, N = 257; VC, N = 46), frozen noise injections (CC, N = 104) and triangular voltage sweeps (VC, 10 (N = 132), 50 (N = 146) and 100 ms (N = 152)), from regular spiking (N = 169) and fast-spiking neurons (N = 66). Conclusions The data can be used to systematically study the properties of somatic integration and the principles of action potential generation across sexes and across electrically characterized neuronal classes in adulthood. Understanding the principles of the somatic transformation of postsynaptic potentials into action potentials will shed light onto the computational principles of intracellular information transfer in single neurons and information processing in neuronal networks, helping to recreate neuronal functions in artificial systems.

Rapid eye movement (REM) sleep is associated with the consolidation of emotional memories. Yet, the underlying neocortical circuits and synaptic mechanisms remain unclear. We found that REM sleep is associated with a somatodendritic decoupling in pyramidal neurons of the prefrontal cortex. This decoupling reflects a shift of inhibitory balance between parvalbumin neuron–mediated somatic inhibition and vasoactive intestinal peptide–mediated dendritic disinhibition, mostly driven by neurons from the central medial thalamus. REM-specific optogenetic suppression of dendritic activity led to a loss of danger-versus-safety discrimination during associative learning and a lack of synaptic plasticity, whereas optogenetic release of somatic inhibition resulted in enhanced discrimination and synaptic potentiation. Somatodendritic decoupling during REM sleep promotes opposite synaptic plasticity mechanisms that optimize emotional responses to future behavioral stressors.

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

Sensory neurons reconstruct the world from action potentials (spikes) impinging on them. Recent work argues that the formation of sensory representations are cell-type specific, as excitatory and inhibitory neurons use complementary information available in spike trains to represent sensory stimuli. Here, by measuring the mutual information between synaptic input and spike trains, we show that inhibitory and excitatory neurons in the barrel cortex transfer information differently: excitatory neurons show strong threshold adaptation and a reduction of intracellular information transfer with increasing firing rates. Inhibitory neurons, on the other hand, show threshold behaviour that facilitates broadband information transfer. We propose that cell-type specific intracellular information transfer is the rate-limiting step for neuronal communication across synaptically coupled networks. Ultimately, at high firing rates, the reduction of information transfer by excitatory neurons and its facilitation by inhibitory neurons together provides a mechanism for sparse coding and information compression in cortical networks.

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

250/250 words)Background : Neurons in the supragranular layers of the somatosensory cortex integrate sensory (bottom-up) and cognitive/perceptual (top-down) information as they orchestrate communication across cortical columns. It has been inferred, based on intracellular recordings from juvenile animals, that supragranular neurons are electrically mature by the fourth postnatal week. However, the dynamics of the neuronal integration in the adulthood is largely unknown. Electrophysiological characterization of the active properties of these neurons throughout adulthood will help to address the biophysical and computational principles of the neuronal integration.Findings : Here we provide a database of whole-cell intracellular recordings from 315 neurons located in the supragranular layers (L2/3) of the primary somatosensory cortex in adult mice (9-45 weeks old) from both sexes (females, N=195; males, N=120). Data include 361 somatic current-clamp (CC) and 476 voltage-clamp (VC) experiments, recorded using a step-and-hold protocol (CC, N=257; VC, N=46), frozen noise injections (CC, N=104) and triangular voltage sweeps (VC, 10 (N=132), 50 (N=146) and 100 ms (N=152)), from regular spiking (N=169) and fast-spiking neurons (N=66).Conclusions : The data can be used to systematically study the properties of somatic integration, and the principles of action potential generation across sexes and across electrically characterized neuronal classes in adulthood. Understanding the principles of the somatic transformation of postsynaptic potentials into action potentials will shed light onto the computational principles of intracellular information transfer in single neurons and information processing in neuronal networks, helping to recreate neuronal functions in artificial systems.

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.