The role of environmental feedback in a brain state switch from passive to active sensing

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Estimating the contribution of assembly activity to cortical dynamics from spike and population measures

The hypothesis that cortical networks employ the coordinated activity of groups of neurons, termed assemblies, to process information is debated. Results from multiple single-unit recordings are not conclusive because of the dramatic undersampling of the system. However, the local field potential (LFP) is a mesoscopic signal reflecting synchronized network activity. This raises the question whether the LFP can be employed to overcome the problem of undersampling. In a recent study in the motor cortex of the awake behaving monkey based on the locking of coincidences to the LFP we determined a lower bound for the fraction of spike coincidences originating from assembly activation. This quantity together with the locking of single spikes leads to a lower bound for the fraction of spikes originating from any assembly activity. Here we derive a statistical method to estimate the fraction of spike synchrony caused by assemblies—not its lower bound—from the spike data alone. A joint spike and LFP surrogate data model demonstrates consistency of results and the sensitivity of the method. Combining spike and LFP signals, we obtain an estimate of the fraction of spikes resulting from assemblies in the experimental data

Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity

The skin is equipped with specialized mechanoreceptors that allow the perception of the slightest brush. Indeed, some mechanoreceptors can detect even nanometer-scale movements. Movement is transformed into electrical signals via the gating of mechanically activated ion channels at sensory endings in the skin. The sensitivity of Piezo mechanically gated ion channels is controlled by stomatin-like protein-3 (STOML3), which is required for normal mechanoreceptor function. Here we identify small-molecule inhibitors of STOML3 oligomerization that reversibly reduce the sensitivity of mechanically gated currents in sensory neurons and silence mechanoreceptors $\textit{in vivo}$. STOML3 inhibitors in the skin also reversibly attenuate fine touch perception in normal mice. Under pathophysiological conditions following nerve injury or diabetic neuropathy, the slightest touch can produce pain, and here STOML3 inhibitors can reverse mechanical hypersensitivity. Thus, small molecules applied locally to the skin can be used to modulate touch and may represent peripherally available drugs to treat tactile-driven pain following neuropathy.This study was funded by DFG collaborative research grant SFB958 (projects A09 to K.P. and G.R.L., A01 to V.H. and Z02 to J.S.). Additional support was provided by a senior ERC grant (grant number 294678 to G.R.L.) and by the NeuroCure Cluster of Excellence (to V.H., G.R.L. and J.F.A.P.). K.P. was supported by a Cecile-Vogt Fellowship (MDC). S.P. was supported by a Marie Curie Fellowship from the European Union (grant number 253663 Touch in situ). C.P. received a Ph.D. fellowship from the University of Cagliari. J.F.A.P. was funded by a European Research Council (ERC) starting grant (ERC-2010-StG-260590), the DFG (FOR 1341, FOR 2143), the Berlin Institute of Health (BIH) and the European Union (FP7, 3x3Dimaging 323945). R.K. was supported by an ERC Advanced Investigator grant (294293-PAIN PLASTICITY). D.H. was funded by the Berlin Institute of Health (BIH). E.St.J.S., L.E. and M.M. were supported by an Alexander von Humboldt Fellowship

A theory of how active behavior stabilises neural activity: neural gain modulation by closed-loop environmental feedback

During active behaviours like running, swimming, whisking or sniffing, motor actions shape sensory input and sensory percepts guide future motor commands. Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and, it has been argued, for perceptual processes. This closed-loop feedback is mediated by brainwide neural circuits but how the presence of feedback signals impacts on the dynamics and function of neurons is not well understood. Here we present a simple theory suggesting that closed-loop feedback between the brain/body/environment can modulate neural gain and, consequently, change endogenous neural fluctuations and responses to sensory input. We support this theory with modeling and data analysis in two vertebrate systems. First, in a model of rodent whisking we show that negative feedback mediated by whisking vibrissa can suppress coherent neural fluctuations and neural responses to sensory input in the barrel cortex. We argue this suppression provides an appealing account of a brain state transition (a marked change in global brain activity) coincident with the onset of whisking in rodents. Moreover, this mechanism suggests a novel signal detection mechanism that selectively accentuates active, rather than passive, whisker touch signals. This mechanism is consistent with a predictive coding strategy that is sensitive to the consequences of motor actions rather than the difference between the predicted and actual sensory input. We further support the theory by re-analysing previously published two-photon data recorded in zebrafish larvae performing closed-loop optomotor behaviour in a virtual swim simulator. We show, as predicted by this theory, that the degree to which each cell contributes in linking sensory and motor signals well explains how much its neural fluctuations are suppressed by closed-loop optomotor behaviour. More generally we argue that our results demonstrate the dependence of neural fluctuations, across the brain, on closed-loop brain/body/environment interactions strongly supporting the idea that brain function cannot be fully understood through open-loop approaches alone

Phonotactic response of female crickets on the Kramer treadmill: methodology, sensory and behavioural implications

Since population-level variation in female mating preferences can shape intraspecific communication systems within the context of sexual selection it is essential to quantify these preferences and their sources of variation. We calculated individual female response functions for four male calling song traits in the field cricket Gryllus bimaculatus, by performing untethered phonotaxis measurements on a spherical locomotor compensator (Kramer treadmill). Firstly, we quantify the population-level sources of phonotactic variation and correct for factors that adversely affect this measurement. Secondly, we develop methodology for the characterisation of individual female phonotactic response functions suitable for population-level analyses and demonstrate the applicability of our method with respect to recent literature on Orthopteran acoustic communication. Phonotaxis towards a preferred stimulus on different occasions is highly repeatable, with lower repeatabilities away from the most preferred signal traits. For certain male signal traits, female preference and selectivity are highly repeatable. Although phonotactic response magnitude deteriorated with age, preference functions of females remained the same during their lifetimes. Finally, the limitations of measuring phonotaxis using a spherical locomotor compensator are described and discussed with respect to the estimation of the selectivity of female response

Nobody Is Perfect: ERP Effects Prior to Performance Errors in Musicians Indicate Fast Monitoring Processes

Background: One central question in the context of motor control and action monitoring is at what point in time errors can be detected. Previous electrophysiological studies investigating this issue focused on brain potentials elicited after erroneous responses, mainly in simple speeded response tasks. In the present study, we investigated brain potentials before the commission of errors in a natural and complex situation. Methodology/Principal Findings: Expert pianists bimanually played scales and patterns while the electroencephalogram (EEG) was recorded. Event-related potentials (ERPs) were computed for correct and incorrect performances. Results revealed differences already 100 ms prior to the onset of a note (i.e., prior to auditory feedback). We further observed that erroneous keystrokes were delayed in time and pressed more slowly. Conclusions: Our data reveal neural mechanisms in musicians that are able to detect errors prior to the execution of erroneous movements. The underlying mechanism probably relies on predictive control processes that compare the predicted outcome of an action with the action goal

Balanced Synaptic Input Shapes the Correlation between Neural Spike Trains

Stimulus properties, attention, and behavioral context influence correlations between the spike times produced by a pair of neurons. However, the biophysical mechanisms that modulate these correlations are poorly understood. With a combined theoretical and experimental approach, we show that the rate of balanced excitatory and inhibitory synaptic input modulates the magnitude and timescale of pairwise spike train correlation. High rate synaptic inputs promote spike time synchrony rather than long timescale spike rate correlations, while low rate synaptic inputs produce opposite results. This correlation shaping is due to a combination of enhanced high frequency input transfer and reduced firing rate gain in the high input rate state compared to the low state. Our study extends neural modulation from single neuron responses to population activity, a necessary step in understanding how the dynamics and processing of neural activity change across distinct brain states

Oral l-menthol reduces thermal sensation, increases work-rate and extends time to exhaustion, in the heat at a fixed rating of perceived exertion

PurposeThe study investigated the effect of a non-thermal cooling agent, l-menthol, on exercise at a fixed subjective rating of perceived exertion (RPE) in a hot environment.MethodEight male participants completed two trials at an exercise intensity between ‘hard’ and ‘very hard’, equating to 16 on the RPE scale at ~35 °C. Participants were instructed to continually adjust their power output to maintain an RPE of 16 throughout the exercise trial, stopping once power output had fallen by 30%. In a randomized crossover design, either l-menthol or placebo mouthwash was administered prior to exercise and at 10 min intervals. Power output, VO2, heart rate, core and skin temperature was monitored, alongside thermal sensation and thermal comfort. Isokinetic peak power sprints were conducted prior to and immediately after the fixed RPE trial.ResultsExercise time was greater (23:23 ± 3:36 vs. 21:44 ± 2:32 min; P = 0.049) and average power output increased (173 ± 24 vs. 167 ± 24 W; P = 0.044) in the l-menthol condition. Peak isokinetic sprint power declined from pre-post trial in the l-menthol l (9.0%; P = 0.015) but not in the placebo condition (3.4%; P = 0.275). Thermal sensation was lower in the l-menthol condition (P = 0.036), despite no changes in skin or core temperature (P > 0.05).Conclusion These results indicate that a non-thermal cooling mouth rinse lowered thermal sensation, resulting in an elevated work rate, which extended exercise time in the heat at a fixed RPE