Simon Peron

Neural Activity in Barrel Cortex Underlying Vibrissa-Based Object Localization in Mice

Classical studies have related the spiking of selected neocortical neurons to behavior, but little is known about activity sampled from the entire neural population. We recorded from neurons selected independent of spiking, using cell-attached recordings and two-photon calcium imaging, in the barrel cortex of mice performing an object localization task. Spike rates varied across neurons, from silence to >60 Hz. Responses were diverse, with some neurons showing large increases in spike rate when whiskers contacted the object. Nearly half the neurons discriminated object location; a small fraction of neurons discriminated perfectly. More active neurons were more discriminative. Layer (L) 4 and L5 contained the highest fractions of discriminating neurons (∼63% and 79%, respectively), but a few L2/3 neurons were also highly discriminating. Approximately 13,000 spikes per activated barrel column were available to mice for decision making. Coding of object location in the barrel cortex is therefore highly redundant.

Multiple dynamic representations in the motor cortex during sensorimotor learning

The mechanisms linking sensation and action during learning are poorly understood. Layer 2/3 neurons in the motor cortex might participate in sensorimotor integration and learning; they receive input from sensory cortex and excite deep layer neurons, which control movement. Here we imaged activity in the same set of layer 2/3 neurons in the motor cortex over weeks, while mice learned to detect objects with their whiskers and report detection with licking. Spatially intermingled neurons represented sensory (touch) and motor behaviours (whisker movements and licking). With learning, the population-level representation of task-related licking strengthened. In trained mice, population-level representations were redundant and stable, despite dynamism of single-neuron representations. The activity of a subpopulation of neurons was consistent with touch driving licking behaviour. Our results suggest that ensembles of motor cortex neurons couple sensory input to multiple, related motor programs during learning.

A Cellular Resolution Map of Barrel Cortex Activity during Tactile Behavior

Comprehensive measurement of neural activity remains challenging due to the large numbers of neurons in each brain area. We used volumetric two-photon imaging in mice expressing GCaMP6s and nuclear red fluorescent proteins to sample activity in 75% of superficial barrel cortex neurons across the relevant cortical columns, approximately 12,000 neurons per animal, during performance of a single whisker object localization task. Task-related activity peaked during object palpation. An encoding model related activity to behavioral variables. In the column corresponding to the spared whisker, 300 layer (L) 2/3 pyramidal neurons (17%) each encoded touch and whisker movements. Touch representation declined by half in surrounding columns; whisker movement representation was unchanged. Following the emergence of stereotyped task-related movement, sensory representations showed no measurable plasticity. Touch direction was topographically organized, with distinct organization for passive and active touch. Our work reveals sparse and spatially intermingled representations of multiple tactile features. VIDEO ABSTRACT.

Procedures for behavioral experiments in head-fixed mice

The mouse is an increasingly prominent model for the analysis of mammalian neuronal circuits. Neural circuits ultimately have to be probed during behaviors that engage the circuits. Linking circuit dynamics to behavior requires precise control of sensory stimuli and measurement of body movements. Head-fixation has been used for behavioral research, particularly in non-human primates, to facilitate precise stimulus control, behavioral monitoring and neural recording. However, choice-based, perceptual decision tasks by head-fixed mice have only recently been introduced. Training mice relies on motivating mice using water restriction. Here we describe procedures for head-fixation, water restriction and behavioral training for head-fixed mice, with a focus on active, whisker-based tactile behaviors. In these experiments mice had restricted access to water (typically 1 ml/day). After ten days of water restriction, body weight stabilized at approximately 80% of initial weight. At that point mice were trained to discriminate sensory stimuli using operant conditioning. Head-fixed mice reported stimuli by licking in go/no-go tasks and also using a forced choice paradigm using a dual lickport. In some cases mice learned to discriminate sensory stimuli in a few trials within the first behavioral session. Delay epochs lasting a second or more were used to separate sensation (e.g. tactile exploration) and action (i.e. licking). Mice performed a variety of perceptual decision tasks with high performance for hundreds of trials per behavioral session. Up to four months of continuous water restriction showed no adverse health effects. Behavioral performance correlated with the degree of water restriction, supporting the importance of controlling access to water. These behavioral paradigms can be combined with cellular resolution imaging, random access photostimulation, and whole cell recordings.

From cudgel to scalpel: toward precise neural control with optogenetics

Optogenetics is routinely used to activate and inactivate genetically defined neuronal populations in vivo. A second optogenetic revolution will occur when spatially distributed and sparse neural assemblies can be precisely manipulated in behaving animals.

Automated tracking of whiskers in videos of head fixed rodents

We have developed software for fully automated tracking of vibrissae (whiskers) in high-speed videos (>500 Hz) of head-fixed, behaving rodents trimmed to a single row of whiskers. Performance was assessed against a manually curated dataset consisting of 1.32 million video frames comprising 4.5 million whisker traces. The current implementation detects whiskers with a recall of 99.998% and identifies individual whiskers with 99.997% accuracy. The average processing rate for these images was 8 Mpx/s/cpu (2.6 GHz Intel Core2, 2 GB RAM). This translates to 35 processed frames per second for a 640 px×352 px video of 4 whiskers. The speed and accuracy achieved enables quantitative behavioral studies where the analysis of millions of video frames is required. We used the software to analyze the evolving whisking strategies as mice learned a whisker-based detection task over the course of 6 days (8148 trials, 25 million frames) and measure the forces at the sensory follicle that most underlie haptic perception.

Comprehensive imaging of cortical networks.

Neural computations are implemented by activity in spatially distributed neural circuits. Cellular imaging fills a unique niche in linking activity of specific types of neurons to behavior, over spatial scales spanning single neurons to entire brain regions, and temporal scales from milliseconds to months. Imaging may soon make it possible to track activity of all neurons in a brain region, such as a cortical column. We review recent methodological advances that facilitate optical imaging of neuronal populations in vivo, with an emphasis on calcium imaging using protein indicators in mice. We point out areas that are particularly ripe for future developments.

Precise Subcellular Input Retinotopy and Its Computational Consequences in an Identified Visual Interneuron

The Lobula Giant Movement Detector (LGMD) is a higher-order visual interneuron of Orthopteran insects that responds preferentially to objects approaching on a collision course. It receives excitatory input from an entire visual hemifield that anatomical evidence suggests is retinotopic. We show that this excitatory projection activates calcium-permeable nicotinic acetylcholine receptors. In vivo calcium imaging reveals that the excitatory projection preserves retinotopy down to the level of a single ommatidium. Examining the impact of retinotopy on the LGMDs computational properties, we show that sublinear synaptic summation can explain orientation preference in this cell. Exploring retinotopys impact on directional selectivity leads us to infer that the excitatory input to the LGMD is intrinsically directionally selective. Our results show that precise retinotopy has implications for the dendritic integration of visual information in a single neuron.

Neurodata Without Borders: Creating a Common Data Format for Neurophysiology

The Neurodata Without Borders (NWB) initiative promotes data standardization in neuroscience to increase research reproducibility and opportunities. In the first NWB pilot project, neurophysiologists and software developers produced a common data format for recordings and metadata of cellular electrophysiology and optical imaging experiments. The format specification, application programming interfaces, and sample datasets have been released.

Role of spike-frequency adaptation in shaping neuronal response to dynamic stimuli

Spike-frequency adaptation is the reduction of a neuron’s firing rate to a stimulus of constant intensity. In the locust, the Lobula Giant Movement Detector (LGMD) is a visual interneuron that exhibits rapid adaptation to both current injection and visual stimuli. Here, a reduced compartmental model of the LGMD is employed to explore adaptation’s role in selectivity for stimuli whose intensity changes with time. We show that supralinearly increasing current injection stimuli are best at driving a high spike count in the response, while linearly increasing current injection stimuli (i.e., ramps) are best at attaining large firing rate changes in an adapting neuron. This result is extended with in vivo experiments showing that the LGMD’s response to translating stimuli having a supralinear velocity profile is larger than the response to constant or linearly increasing velocity translation. Furthermore, we show that the LGMD’s preference for approaching versus receding stimuli can partly be accounted for by adaptation. Finally, we show that the LGMD’s adaptation mechanism appears well tuned to minimize sensitivity for the level of basal input.