Inhibitory neurons: VIP neurons expect rewards.

Inhibitory neurons which express vasoactive intestinal polypeptide, VIPs, are a small subset of the mammalian cortex but in importance live up to their acronym. New research shows that these critical control knobs of cortical activity are specifically activated by actions taken when rewards are anticipated rather than consummated.

Independent representations of self-motion and object location in barrel cortex output.

During active tactile exploration, the dynamic patterns of touch are transduced to electrical signals and transformed by the brain into a mental representation of the object under investigation. This transformation from sensation to perception is thought to be a major function of the mammalian cortex. In primary somatosensory cortex (S1) of mice, layer 5 (L5) pyramidal neurons are major outputs to downstream areas that influence perception, decision-making, and motor control.

Behavioral and Neural Bases of Tactile Shape Discrimination Learning in Head-Fixed Mice.

Tactile shape recognition requires the perception of object surface angles. We investigate how neural representations of object angles are constructed from sensory input and how they reorganize across learning. Head-fixed mice learned to discriminate object angles by active exploration with one whisker.

Touch: Fluctuating Waves of Perception.

Does sensory input flow into the brain as a stream, or does it come in waves? New research shows that tactile information in the cortex rises and falls in phase with the forward and back motion of whiskers during surface exploration.

The Sensorimotor Basis of Whisker-Guided Anteroposterior Object Localization in Head-Fixed Mice.

Active tactile perception combines directed motion with sensory signals to generate mental representations of objects in space. Competing models exist for how mice use these signals to determine the precise location of objects along their face. We tested six of these models using behavioral manipulations and statistical learning in head-fixed mice.

Dynamic cues for whisker-based object localization: An analytical solution to vibration during active whisker touch.

Vibrations are important cues for tactile perception across species. Whisker-based sensation in mice is a powerful model system for investigating mechanisms of tactile perception. However, the role vibration plays in whisker-based sensation remains unsettled, in part due to difficulties in modeling the vibration of whiskers.

Mechanisms underlying a thalamocortical transformation during active tactile sensation.

During active somatosensation, neural signals expected from movement of the sensors are suppressed in the cortex, whereas information related to touch is enhanced. This tactile suppression underlies low-noise encoding of relevant tactile features and the brain's ability to make fine tactile discriminations. Layer (L) 4 excitatory neurons in the barrel cortex, the major target of the somatosensory thalamus (VPM), respond to touch, but have low spike rates and low sensitivity to the movement of whiskers.

Beyond cones: an improved model of whisker bending based on measured mechanics and tapering.

The sense of touch is represented by neural activity patterns evoked by mechanosensory input forces. The rodent whisker system is exceptional for studying the neurophysiology of touch in part because these forces can be precisely computed from video of whisker deformation. We evaluate the accuracy of a standard model of whisker bending, which assumes quasi-static dynamics and a linearly tapered conical profile, using controlled whisker deflections.

Neural coding in barrel cortex during whisker-guided locomotion.

Animals seek out relevant information by moving through a dynamic world, but sensory systems are usually studied under highly constrained and passive conditions that may not probe important dimensions of the neural code. Here, we explored neural coding in the barrel cortex of head-fixed mice that tracked walls with their whiskers in tactile virtual reality. Optogenetic manipulations revealed that barrel cortex plays a role in wall-tracking.

Low-noise encoding of active touch by layer 4 in the somatosensory cortex.

Cortical spike trains often appear noisy, with the timing and number of spikes varying across repetitions of stimuli. Spiking variability can arise from internal (behavioral state, unreliable neurons, or chaotic dynamics in neural circuits) and external (uncontrolled behavior or sensory stimuli) sources. The amount of irreducible internal noise in spike trains, an important constraint on models of cortical networks, has been difficult to estimate, since behavior and brain state must be precisely controlled or tracked.

Tapered whiskers are required for active tactile sensation.

Many mammals forage and burrow in dark constrained spaces. Touch through facial whiskers is important during these activities, but the close quarters makes whisker deployment challenging. The diverse shapes of facial whiskers reflect distinct ecological niches.

Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss.

Synaptic loss is the cardinal feature linking neuropathology to cognitive decline in Alzheimer's disease (AD). However, the mechanism of synaptic damage remains incompletely understood. Here, using FRET-based glutamate sensor imaging, we show that amyloid-β peptide (Aβ) engages α7 nicotinic acetylcholine receptors to induce release of astrocytic glutamate, which in turn activates extrasynaptic NMDA receptors (eNMDARs) on neurons.

Concurrent imaging of synaptic vesicle recycling and calcium dynamics.

Synaptic transmission involves the calcium dependent release of neurotransmitter from synaptic vesicles. Genetically encoded optical probes emitting different wavelengths of fluorescent light in response to neuronal activity offer a powerful approach to understand the spatial and temporal relationship of calcium dynamics to the release of neurotransmitter in defined neuronal populations. To simultaneously image synaptic vesicle recycling and changes in cytosolic calcium, we developed a red-shifted reporter of vesicle recycling based on a vesicular glutamate transporter, VGLUT1-mOrange2 (VGLUT1-mOr2), and a presynaptically localized green calcium indicator, synaptophysin-GCaMP3 (SyGCaMP3) with a large dynamic range.

Optical measurement of synaptic glutamate spillover and reuptake by linker optimized glutamate-sensitive fluorescent reporters.

Genetically encoded sensors of glutamate concentration are based on FRET between cyan and yellow fluorescent proteins bracketing a bacterial glutamate-binding protein. Such sensors have yet to find quantitative applications in neurons, because of poor response amplitude in physiological buffers or when expressed on the neuronal cell surface. We have improved our glutamate-sensing fluorescent reporter (GluSnFR) by systematic optimization of linker sequences and glutamate affinities.