Valérie Ego-Stengel

Disruption of ripple-associated hippocampal activity during rest impairs spatial learning in the rat.

The hippocampus plays a key role in the acquisition of new memories for places and events. Evidence suggests that the consolidation of these memories is enhanced during sleep. At the neuronal level, reactivation of awake experience in the hippocampus during sharp‐wave ripple events, characteristic of slow‐wave sleep, has been proposed as a neural mechanism for sleep‐dependent memory consolidation. However, a causal relation between sleep reactivation and memory consolidation has not been established. Here we show that disrupting neuronal activity during ripple events impairs spatial learning. We trained rats daily in two identical spatial navigation tasks followed each by a 1‐hour rest period. After one of the tasks, stimulation of hippocampal afferents selectively disrupted neuronal activity associated with ripple events without changing the sleep‐wake structure. Rats learned the control task significantly faster than the task followed by rest stimulation, indicating that interfering with hippocampal processing during sleep led to decreased learning.

Emergent properties of tactile scenes selectively activate barrel cortex neurons.

Rats discriminate objects by scanning their surface with the facial vibrissae, producing spatiotemporally complex sequences of tactile contacts. The way in which the somatosensory cortex responds to these complex multivibrissal stimuli has not been explored. It is unclear yet whether contextual information from across the entire whisker pad influences cortical responses. Here, we delivered tactile stimuli to the rat vibrissae using a new 24 whisker stimulator. We tested sequences of rostrocaudal whisker deflections that generate multivibrissal motion patterns in different directions across the mystacial pad, allowing to disambiguate local from global sensory integration. Unitary electrophysiological recordings from different layers of the barrel cortex showed that a majority of neurons has direction selectivity for the multivibrissal stimulus. The selectivity resulted from nonlinear integration of responses across the mystacial pad. Our results indicate that the system extracts collective properties of a tactile scene.

NORADRENERGIC MODULATION OF FUNCTIONAL SELECTIVITY IN THE CAT VISUAL CORTEX: AN IN VIVO EXTRACELLULAR AND INTRACELLULAR STUDY

In vitro intracellular studies have shown that norepinephrine modulates cellular excitability and synaptic transmission in the cortex. Based on these effects, norepinephrine has been proposed to enhance the signal-to-noise ratio and to improve functional selectivity by potentiating strong synaptic responses and reducing weak ones. Here we have studied the functional effects of iontophoretic applications of norepinephrine during in vivo extracellular and intracellular recordings from neurons of the primary visual cortex of kittens and adult cats. Analysis of extracellular data concentrated on norepinephrine-induced changes in spontaneous and evoked activities, in signal-to-noise ratio, and in orientation and direction selectivity. Analysis of the intracellular data concentrated on actions of norepinephrine on spike firing accommodation, which has been shown to be reduced by norepinephrine in vitro, and on synaptic responses. Application of norepinephrine resulted in a depression of both spontaneous and evoked spiking activity. However, no systematic change in signal-to-noise ratio was observed. The suppressive effect of norepinephrine was exerted with no significant sharpening of direction or orientation selectivity tuning. The overall reduction in visual activity by norepinephrine affected the orientation tuning curves in a way compatible with a divisive effect, that is a normalization or gain control with no change in tuning width. Norepinephrine applied during intracellular recordings reduced the visually evoked depolarizing potentials whereas no change in the responsiveness of the cell to current-induced depolarizations was observed. In conditions of optimal visual stimulation which produced large depolarizations of several hundreds of milliseconds and sustained repetitive firing comparable to that obtained by direct current injection, we were unable to observe a facilitation of the evoked responses by norepinephrine as it would be expected from the well-documented increase in excitability induced by norepinephrine in vitro. In conclusion, from these results we suggest that norepinephrine released in the primary visual cortex primarily reduces the level of cortical activation by afferent signals, without affecting the cortical functional selectivity nor increasing the signal-to-noise ratio.

“Master” Neurons Induced by Operant Conditioning in Rat Motor Cortex during a Brain-Machine Interface Task

Operant control of a prosthesis by neuronal cortical activity is one of the successful strategies for implementing brain-machine interfaces (BMI), by which the subject learns to exert a volitional control of goal-directed movements. However, it remains unknown if the induced brain circuit reorganization affects preferentially the conditioned neurons whose activity controlled the BMI actuator during training. Here, multiple extracellular single-units were recorded simultaneously in the motor cortex of head-fixed behaving rats. The firing rate of a single neuron was used to control the position of a one-dimensional actuator. Each time the firing rate crossed a predefined threshold, a water bottle moved toward the rat, until the cumulative displacement of the bottle allowed the animal to drink. After a learning period, most (88%) conditioned neurons raised their activity during the trials, such that the time to reward decreased across sessions: the conditioned neuron fired strongly, reliably and swiftly after trial onset, although no explicit instruction in the learning rule imposed a fast neuronal response. Moreover, the conditioned neuron fired significantly earlier and more strongly than nonconditioned neighboring neurons. During the first training sessions, an increase in firing rate variability was seen only for the highly conditionable neurons. This variability then decreased while the conditioning effect increased. These findings suggest that modifications during training target preferentially the neuron chosen to control the BMI, which acts then as a “master” neuron, leading in time the reconfiguration of activity in the local cortical network.

Coding of Apparent Motion in the Thalamic Nucleus of the Rat Vibrissal Somatosensory System

While exploring objects, rats make multiple contacts using their whiskers, thereby generating complex patterns of sensory information. The cerebral structures that process this information in the somatosensory system show discrete patterns of anatomically distinct units, each corresponding to one whisker. Moreover, the feedforward and feedback connections are remarkably topographic, with little cross-whisker divergence before reaching the cortical network. Despite this parallel design, information processing from several whiskers has been reported in subcortical nuclei. Here, we explored whether sensory neurons in the ventral posterior medial nucleus (VPM) of the thalamus encode emergent properties of complex multiwhisker stimulations. Using a 24-whisker stimulator, we tested the responses of VPM neurons to sequences of caudal deflections that generated an apparent motion in eight different directions across the whiskerpad. Overall, 45% of neurons exhibited an evoked increase in firing rate significantly selective to the direction of apparent motion of the global stimulus. Periods of suppression of firing rate were often observed, but were generally not selective. Global motion selectivity of VPM neurons could occur regardless of the extent and spatial organization of their receptive fields, and of their selectivity for the direction of motion of their principal whisker. To investigate whether the global selectivity could be due to corticothalamic feedback connections, we inactivated the barrel cortex while repeating the stimulation protocol. For most VPM neurons, the direction selectivity decreased but was still present. These results suggest that nonlinear processing of stimuli from different whiskers emerges in subcortical nuclei and is amplified by the corticofugal feedback.

Representation of Tactile Scenes in the Rodent Barrel Cortex

After half a century of research, the sensory features coded by neurons of the rodent barrel cortex remain poorly understood. Still, views of the sensory representation of whisker information are increasingly shifting from a labeled line representation of single-whisker deflections to a selectivity for specific elements of the complex statistics of the multi-whisker deflection patterns that take place during spontaneous rodent behavior - so called natural tactile scenes. Here we review the current knowledge regarding the coding of patterns of whisker stimuli by barrel cortex neurons, from responses to single-whisker deflections to the representation of complex tactile scenes. A number of multi-whisker tunings have already been identified, including center-surround feature extraction, angular tuning during edge-like multi-whisker deflections, and even tuning to specific statistical properties of the tactile scene such as the level of correlation across whiskers. However, a more general model of the representation of multi-whisker information in the barrel cortex is still missing. This is in part because of the lack of a human intuition regarding the perception emerging from a whisker system, but also because in contrast to other primary sensory cortices such as the visual cortex, the spatial feature selectivity of barrel cortex neurons rests on highly nonlinear interactions that remained hidden to classical receptive field approaches.

Bilateral Discrimination of Tactile Patterns without Whisking in Freely Running Rats

A majority of whisker discrimination tasks in rodents are performed on head-fixed animals to facilitate tracking or control of the sensory inputs. However, head fixation critically restrains the behavior and thus the incoming stimuli compared with those occurring in natural conditions. In this study, we investigated whether freely behaving rats can discriminate fine tactile patterns while running, in particular when stimuli are presented simultaneously on both sides of the snout. We developed a two-alternative forced-choice task in an automated modified T-maze. Stimuli were either a surface with no bars (smooth) or with vertical bars spaced irregularly or regularly. While running at full speed, rats encountered simultaneously the two discriminanda placed on the two sides of the central aisle. Rats learned to recognize regular bars versus a smooth surface in 8 weeks. They solved the task while running at an average speed of 1 m/s, so that the contact with the stimulus lasted <1 typical whisking cycle, precluding the use of active whisking. Whisker-tracking analysis revealed an asymmetry in the position of the whiskers: they oriented toward the rewarded stimulus during successful trials as early as 60 ms after the first possible contact. We showed that the whiskers and activity in the primary somatosensory cortex are involved during the discrimination process. Finally, we identified irregular patterns of bars that the rats can discriminate from the regular one. This novel task shows that freely moving rodents can make simultaneous bilateral tactile discrimination without whisking. SIGNIFICANCE STATEMENT The whisker system of rodents is a widely used model to study tactile processing. Rats show remarkable abilities in discriminating surfaces by actively moving their whiskers (whisking) against stimuli, typically sampling them several times. This motor strategy affects considerably the way that tactile information is acquired and thus the way that neuronal networks process the information. However, when rats run at high speed, they protract their whiskers in front of the snout without large movements. Here, we investigated whether rats are able to discriminate regular and irregular patterns of vertical bars while running without whisking. We found that the animals can perform a bilateral simultaneous discrimination without whisking and that this involves both whiskers and barrel cortex activity.

Bidirectional control of a one-dimensional robotic actuator by operant conditioning of a single unit in rat motor cortex

The design of efficient neuroprosthetic devices has become a major challenge for the long-term goal of restoring autonomy to motor-impaired patients. One approach for brain control of actuators consists in decoding the activity pattern obtained by simultaneously recording large neuronal ensembles in order to predict in real-time the subjects intention, and move the prosthesis accordingly. An alternative way is to assign the output of one or a few neurons by operant conditioning to control the prosthesis with rules defined by the experimenter, and rely on the functional adaptation of these neurons during learning to reach the desired behavioral outcome. Here, several motor cortex neurons were recorded simultaneously in head-fixed awake rats and were conditioned, one at a time, to modulate their firing rate up and down in order to control the speed and direction of a one-dimensional actuator carrying a water bottle. The goal was to maintain the bottle in front of the rats mouth, allowing it to drink. After learning, all conditioned neurons modulated their firing rate, effectively controlling the bottle position so that the drinking time was increased relative to chance. The mean firing rate averaged over all bottle trajectories depended non-linearly on position, so that the mouth position operated as an attractor. Some modifications of mean firing rate were observed in the surrounding neurons, but to a lesser extent. Notably, the conditioned neuron reacted faster and led to a better control than surrounding neurons, as calculated by using the activity of those neurons to generate simulated bottle trajectories. Our study demonstrates the feasibility, even in the rodent, of using a motor cortex neuron to control a prosthesis in real-time bidirectionally. The learning process includes modifications of the activity of neighboring cortical neurons, while the conditioned neuron selectively leads the activity patterns associated with the prosthesis control.

A fast intracortical brain–machine interface with patterned optogenetic feedback

OBJECTIVE The development of brain-machine interfaces (BMIs) brings new prospects to patients with a loss of autonomy. By combining online recordings of brain activity with a decoding algorithm, patients can learn to control a robotic arm in order to perform simple actions. However, in contrast to the vast amounts of somatosensory information channeled by limbs to the brain, current BMIs are devoid of touch and force sensors. Patients must therefore rely solely on vision and audition, which are maladapted to the control of a prosthesis. In contrast, in a healthy limb, somatosensory inputs alone can efficiently guide the handling of a fragile object, or ensure a smooth trajectory. We have developed a BMI in the mouse that includes a rich artificial somatosensory-like cortical feedback. APPROACH Our setup includes online recordings of the activity of multiple neurons in the whisker primary motor cortex (vM1) and delivers feedback simultaneously via a low-latency, high-refresh-rate, spatially structured photo-stimulation of the whisker primary somatosensory cortex (vS1), based on a mapping obtained by intrinsic imaging. MAIN RESULTS We demonstrate the operation of the loop and show that mice can detect the neuronal spiking in vS1 triggered by the photo-stimulations. Finally, we show that the mice can learn a behavioral task relying solely on the artificial inputs and outputs of the closed-loop BMI. SIGNIFICANCE This is the first motor BMI that includes a short-latency, intracortical, somatosensory-like feedback. It will be a useful platform to discover efficient cortical feedback schemes towards future human BMI applications.

S1 Long-Term Plasticity

S1 long-term plasticity refers to persistent modifications in the structure or functioning of the primary somatosensory cortex (S1). These modifications are proposed to underlie learning and memory of tactile information, as well as recovery of function after injury.