Optogenetic Activation of Dorsal Raphe Serotonin Neurons Rapidly Inhibits Spontaneous But Not Odor-Evoked Activity in Olfactory Cortex

Serotonin (5-hydroxytriptamine; 5-HT) is implicated in a variety of brain functions including not only the regulation of mood and control of behavior but also the modulation of perception. 5-HT neurons in the dorsal raphe nucleus (DRN) often fire locked to sensory stimuli, but little is known about how 5-HT affects sensory processing, especially on this timescale. Here, we used an optogenetic approach to study the effect of 5-HT on single-unit activity in the mouse primary olfactory (anterior piriform) cortex. We show that activation of DRN 5-HT neurons rapidly inhibits the spontaneous firing of olfactory cortical neurons, acting in a divisive manner, but entirely spares sensory-driven firing. These results identify a new role for serotonergic modulation in dynamically regulating the balance between different sources of neural activity in sensory systems, suggesting a possible role for 5-HT in perceptual inference.info:eu-repo/semantics/publishedVersio

Locus coeruleus norepinephrine activity mediates sensory-evoked awakenings from sleep

A defining feature of sleep is reduced responsiveness to external stimuli, but the mechanisms mediating sensory-evoked arousal remain unclear. We hypothesized that reduced locus coeruleus (LC) norepinephrine (NE) activity during sleep mediates unresponsiveness, and its action promotes sensory-evoked awakenings. We tested this using electrophysiological, behavioral, pharmacological, and optogenetic techniques alongside auditory stimulation in freely behaving rats. We found that systemic reduction in NE signaling lowered probability of sound-evoked awakenings (SEAs). The level of tonic LC activity during sleep anticipated SEAs. Optogenetic LC activation promoted arousal as evident in sleep-wake transitions, EEG desynchronization, and pupil dilation. Minimal LC excitation before sound presentation increased SEA probability. Optogenetic LC silencing using a soma-targeted anion-conducting channelrhodopsin (stGtACR2) suppressed LC spiking and constricted pupils. Brief periods of LC opto-silencing reduced the probability of SEAs. Thus, LC-NE activity determines the likelihood of sensory-evoked awakenings, and its reduction during sleep constitutes a key factor mediating behavioral unresponsiveness.This work was supported by the Israel Science Foundation (ISF) grants 1326/15 and 51/11 (I-CORE cognitive sciences) and the Adelis Foundation (to Y.N.). E.J.K. is an INSERM fellow. O.Y. is supported by the European Research Council (ERC-2013-StG OptoNeuromod 337637) and the Adelis Foundation. CAV2 vector production was supported by CNRS BioCampus (Montpellier). A.S. is a Wellcome Trust-funded PhD student on the Neural Dynamics program. A.J.K. is supported by the ISF grant 762/16 and the European Society of Anaesthesiology young investigator startup gran

Psychometric Curve and Behavioral Strategies for Whisker-Based Texture Discrimination in Rats

The rodent whisker system is a major model for understanding neural mechanisms for tactile sensation of surface texture (roughness). Rats discriminate surface texture using the whiskers, and several theories exist for how texture information is physically sensed by the long, moveable macrovibrissae and encoded in spiking of neurons in somatosensory cortex. However, evaluating these theories requires a psychometric curve for texture discrimination, which is lacking. Here we trained rats to discriminate rough vs. fine sandpapers and grooved vs. smooth surfaces. Rats intermixed trials at macrovibrissa contact distance (nose >2 mm from surface) with trials at shorter distance (nose <2 mm from surface). Macrovibrissae were required for distant contact trials, while microvibrissae and non-whisker tactile cues were used for short distance trials. A psychometric curve was measured for macrovibrissa-based sandpaper texture discrimination. Rats discriminated rough P150 from smoother P180, P280, and P400 sandpaper (100, 82, 52, and 35 µm mean grit size, respectively). Use of olfactory, visual, and auditory cues was ruled out. This is the highest reported resolution for rodent texture discrimination, and constrains models of neural coding of texture information

Behavioral study of whisker-mediated vibration sensation in rats

Rats use their vibrissal sensory system to collect information about the nearby environment. They can accurately and rapidly identify object location, shape, and surface texture. Which features of whisker motion does the sensory system extract to construct sensations? We addressed this question by training rats to make discriminations between sinusoidal vibrations simultaneously presented to the left and right whiskers. One set of rats learned to reliably identify which of two vibrations had higher frequency (f1 vs. f2) when amplitudes were equal. Another set of rats learned to reliably identify which of two vibrations had higher amplitude (A1 vs. A2) when frequencies were equal. Although these results indicate that both elemental features contribute to the rats\u2019 sensation, a further test found that the capacity to discriminate A and f was reduced to chance when the difference in one feature was counterbalanced by the difference in the other feature: Rats could not discriminate amplitude or frequency whenever A1f1 = A2f2. Thus, vibrations were sensed as the product Af rather than as separable elemental features, A and f. The product Af is propor- tional to a physical entity, the mean speed. Analysis of performance revealed that rats extracted more information about differences in Af than predicted by the sum of the information in elemental differences. These behavioral experiments support the predictions of earlier physiological studies by demonstrating that rats are \u201cblind\u201d to the elemental features present in a sinusoidal whisker vibration; instead, they perceive a composite feature, the speed of whisker motion

Pre-neuronal morphological processing of object location by individual whiskers

In the vibrissal system, touch information is conveyed by a receptorless whisker hair to follicle mechanoreceptors, which then provide input to the brain. We examined whether any processing, that is, meaningful transformation, occurs in the whisker itself. Using high-speed videography and tracking the movements of whiskers in anesthetized and behaving rats, we found that whisker-related morphological phase planes, based on angular and curvature variables, can represent the coordinates of object position after contact in a reliable manner, consistent with theoretical predictions. By tracking exposed follicles, we found that the follicle-whisker junction is rigid, which enables direct readout of whisker morphological coding by mechanoreceptors. Finally, we found that our behaving rats pushed their whiskers against objects during localization in a way that induced meaningful morphological coding and, in parallel, improved their localization performance, which suggests a role for pre-neuronal morphological computation in active vibrissal touch

Hippocampal representation of touch-guided behavior in rats: Persistent and independent traces of stimulus and reward location

Understanding the mechanisms by which sensory experiences are stored remains a compelling challenge for neuroscience. Previous work has described how the activity of neurons in the sensory cortex allows rats to discriminate the physical features of an object contacted with their whiskers. But to date there is no evidence about how neurons represent the behavioural significance of tactile stimuli, or how they are encoded in memory. To investigate these issues, we recorded single-unit firing and local field potentials from the CA1 region of hippocampus while rats performed a task in which tactile stimuli specified reward location. On each trial the rat touched a textured plate with its whiskers, and then turned towards the Left or Right water spout. Two textures were associated with each reward location. To determine the influence of the rat's position on sensory coding, we placed it on a second platform in the same room where it performed the identical texture discrimination task. Over 25 percent of the sampled neurons encoded texture identity - their firing differed for two stimuli associated with the same reward location - and over 50 percent of neurons encoded the reward location with which the stimuli were associated. The neuronal population carried texture and reward location signals continuously, from the moment of stimulus contact until the end of reward collection. The set of neurons discriminating between one texture pair was found to be independent of, and partially overlapping, the set of neurons encoding the discrimination between a different texture pair. In a given neuron, the presence of a tactile signal was uncorrelated with the presence, magnitude, or timing of reward location signals. These experiments indicate that neurons in CA1 form a texture representation independently of the action the stimulus is associated with and retain the stimulus representation through reward collection