Serotonin regulates rhythmic whisking

Many rodents explore their environment by rhythmically palpating objects with their mystacial whiskers. These rhythmic whisker movements ("whisking"; 5-9 Hz) are thought to be regulated by an unknown brainstem central pattern generator (CPG). We tested the hypothesis that serotonin (5-HT) inputs to whisking facial motoneurons (wFMNs) are part of this CPG. In response to exogenous serotonin, wFMNs recorded in vitro fire rhythmically at whisking frequencies, and selective 5-HT2 or 5-HT3 receptor antagonists suppress this rhythmic firing. In vivo, stimulation of brainstem serotonergic raphe nuclei evokes whisker movements. Unilateral infusion of selective 5-HT2 or 5-HT3 receptor antagonists suppresses ipsilateral whisking and substantially alters the frequencies and symmetry of whisker movements. These findings suggest that serotonin is both necessary and sufficient to generate rhythmic whisker movements and that serotonergic premotoneurons are part of a whisking CPG.     

Whisker primary afferents encode temporal frequency of moving gratings

To investigate the encoding of behaviorally relevant stimuli in the rodent whisker-somatosensory system, we recorded responses to moving gratings from trigeminal ganglion neurons. This allowed us to quantify how spike patterns in these neurons encode behaviorally distinguishable tactile stimuli presented with the variability inherent in a freely moving whisker paradigm. Our stimulus set consisted of three grating plates with raised bars of the same thickness (275 microm) having different spatial periods (1.0, 1.1, and 1.5 mm) swept rostro-caudally past the whiskers at velocities ranging from 50 to 330 mm/s. This resulted in 20 presentations each of nine different temporal frequencies (ranging from 50 to 220 Hz) for every grating plate. We found that despite the additional degrees of freedom introduced in this freely moving whisker paradigm, firing patterns from the majority (83%) of trigeminal ganglion neurons were statistically distinguishable, and corresponded to the temporal frequency of stimulation. The range of velocities (100-160 mm/s) that resulted in the most accurate and least variable representation of stimulus temporal frequency by trigeminal firing patterns closely corresponds to the whisking velocities employed by trained rats performing similar discrimination tasks. This suggests that, during naturally occurring whisking, individual primary afferents faithfully encode temporal frequency evoked by whisker contacts.     

Coherence between Rat Sensorimotor System and Hippocampus Is Enhanced during Tactile Discrimination

Rhythms with time scales of multiple cycles per second permeate the mammalian brain, yet neuroscientists are not certain of their functional roles. One leading idea is that coherent oscillation between two brain regions facilitates the exchange of information between them. In rats, the hippocampus and the vibrissal sensorimotor system both are characterized by rhythmic oscillation in the theta range, 5–12 Hz. Previous work has been divided as to whether the two rhythms are independent or coherent. To resolve this question, we acquired three measures from rats—whisker motion, hippocampal local field potential (LFP), and barrel cortex unit firing—during a whisker-mediated texture discrimination task and during control conditions (not engaged in a whisker-mediated memory task). Compared to control conditions, the theta band of hippocampal LFP showed a marked increase in power as the rats approached and then palpated the texture. Phase synchronization between whisking and hippocampal LFP increased by almost 50% during approach and texture palpation. In addition, a greater proportion of barrel cortex neurons showed firing that was phase-locked to hippocampal theta while rats were engaged in the discrimination task. Consistent with a behavioral consequence of phase synchronization, the rats identified the texture more rapidly and with lower error likelihood on trials in which there was an increase in theta-whisking coherence at the moment of texture palpation. These results suggest that coherence between the whisking rhythm, barrel cortex firing, and hippocampal LFP is augmented selectively during epochs in which the rat collects sensory information and that such coherence enhances the efficiency of integration of stimulus information into memory and decision-making centers.     

Discriminative whisking in the head-fixed rat: optoelectronic monitoring during tactile detection and discrimination tasks

We compared whisking movement patterns during acquisition of tactile detection and object discrimination under conditions in which (a) head movements are excluded and (b) exposure to tactile discriminanda is confined to the large, moveable vibrissae (macrovibrissae). We used optoelectronic instrumentation to track the movements of an individual whisker with high spatio-temporal resolution and a testing paradigm, which allowed us to dissociate performance on an "indicator" response (lever pressing) from the rat's "observing" responses (discriminative whisking). We analyzed the relation between discrimination performance and whisking movement patterns in order to clarify the process by which the indicator response comes under the stimulus control of information acquired by the rat's whisking behavior. Whisking patterns over the course of task acquisition differed with task demands. Acquisition of the Detection task was correlated with modulation of only one whisking movement parameter-total number of whisks emitted, and more whisking was seen on trials in which the discriminandum was absent. Discrimination between a sphere and cube differing in size and texture was correlated with a reduction in whisk duration and protraction amplitude and with a shift towards higher whisking frequencies. Our findings confirm previous reports that acquisition of tactile discriminations involves modulation by the animal of both the amount and the type of whisking. In contrast with a previous report (Brecht et al., 1997), they indicate that rats can solve tactile object detection and discrimination tasks (a) using only the large, motile mystacial vibrissae (macrovibrissae) and (b) without engaging in head movements. We conclude that the functional contribution of the macrovibrissae will vary with the nature of the task and the conditions of testing.     

Cortical barrel field ablation and unconditioned whisking kinematics

The effects of “barrel cortex” ablation upon the biometrics of “exploratory” whisking were examined in three head-fixed rats which had previously sustained unilateral ablation of the left cortical “barrel field” under electrophysiological control. Unconditioned movements of a pair of bilaterally homologous whiskers (C-1, Right, Left) were monitored, optoelectronically, with other whiskers present. Whisking movements on the intact and ablated side were analyzed with respect to kinematics (protraction amplitude and velocity) whisking frequency and phase relationships between whisking movement on the two sides of the face. Histological analysis confirmed complete removal of S-1 “barrel cortex”. In normal animals whisking movements have a characteristic rhythm (6-9 Hz), and protractions on the two sides of the face tend to be both synchronous and of very similar amplitudes. In the lesioned animals, whisking frequency was unchanged and whisking movements remained bilaterally synchronous. However, there was a significant difference between the amplitude of Right and Left whisker movements which was evident many months postoperatively. Our results suggest that the deficits in vibrissa-mediated tactile discrimination reported after “barrel” field ablation may reflect an impairment in the animal's ability to modulate whisking parameters on the two sides of the face to meet the functional requirements of a discriminative whisking task. The effects upon whisking amplitude seen after unilateral barrel field ablation are consistent with a model in which the activity of a whisking Central Pattern Generator is modulated by descending inputs to achieve sensorimotor control of whisking movement parameters.     

Cortical barrel field ablation and unconditioned whisking kinematics

The effects of "barrel cortex" ablation upon the biometrics of "exploratory" whisking were examined in three head-fixed rats which had previously sustained unilateral ablation of the left cortical "barrel field" under electrophysiological control. Unconditioned movements of a pair of bilaterally homologous whiskers (C-1, Right, Left) were monitored, optoelectronically, with other whiskers present. Whisking movements on the intact and ablated side were analyzed with respect to kinematics (protraction amplitude and velocity) whisking frequency and phase relationships between whisking movement on the two sides of the face. Histological analysis confirmed complete removal of S-1 "barrel cortex". In normal animals whisking movements have a characteristic rhythm (6-9 Hz), and protractions on the two sides of the face tend to be both synchronous and of very similar amplitudes. In the lesioned animals, whisking frequency was unchanged and whisking movements remained bilaterally synchronous. However, there was a significant difference between the amplitude of Right and Left whisker movements which was evident many months postoperatively. Our results suggest that the deficits in vibrissa-mediated tactile discrimination reported after "barrel" field ablation may reflect an impairment in the animal's ability to modulate whisking parameters on the two sides of the face to meet the functional requirements of a discriminative whisking task. The effects upon whisking amplitude seen after unilateral barrel field ablation are consistent with a model in which the activity of a whisking Central Pattern Generator is modulated by descending inputs to achieve sensorimotor control of whisking movement parameters.     

Reversible blockade of rodent whisking: Botulinum toxin as a tool for developmental studies

Studies of sensorimotor systems such as the whisking system of rodents have suggested that associations between body movements and their sensory consequences during development may make an important contribution to the functional organization of the system. In the present study we have explored the possible utility of Botulinum toxin for developmental studies of whisking. Botox selectively blocks whisking-generated afference leaving other sources of whisker afference intact. We describe appropriate modes of injection, define dosage levels, and assess the effects of prolonged whisking paralysis during development upon the basic motor competency of the adult rat. Our findings indicate that: (a) Botulinum toxin may be used to block whisking behavior in adult and developing rats, (b) that the duration of the whisking paralysis produced by Botox treatment blockade is dose dependent in both developing and adult animals, (c) that the blockade is functionally reversible and (d) that Botox treatment during development does not impair either the kinematics or the rhythmic patterning of adult whisking behavior. Botox may be a useful tool for studying the role of experiential factors in the development of "active touch" in rodents.     

Reversible blockade of rodent whisking: Botulinum toxin as a tool for developmental studies

Studies of sensorimotor systems such as the whisking system of rodents have suggested that associations between body movements and their sensory consequences during development may make an important contribution to the functional organization of the system. In the present study we have explored the possible utility of Botulinum toxin for developmental studies of whisking. Botox selectively blocks whisking-generated afference leaving other sources of whisker afference intact. We describe appropriate modes of injection, define dosage levels, and assess the effects of prolonged whisking paralysis during development upon the basic motor competency of the adult rat. Our findings indicate that: (a) Botulinum toxin may be used to block whisking behavior in adult and developing rats, (b) that the duration of the whisking paralysis produced by Botox treatment blockade is dose dependent in both developing and adult animals, (c) that the blockade is functionally reversible and (d) that Botox treatment during development does not impair either the kinematics or the rhythmic patterning of adult whisking behavior. Botox may be a useful tool for studying the role of experiential factors in the development of "active touch" in rodents.     

Topography of rodent whisking--I. Two-dimensional monitoring of whisker movements

During 'active touch' the rodent whiskers scan the environment in a series of repetitive movements ('whisks') generating afferent signals which transform the spatial properties of objects into spatio-temporal patterns of neural activity. Based upon analyses carried out in a single movement plane, it has been generally assumed that these trajectories are essentially uni-dimensional, although more complex movements have been described in some rodents. The present study was designed to examine this assumption and to more precisely characterize whisking topography by monitoring whisking trajectories along both the antero-posterior and dorso-ventral axes. Using optoelectronic monitoring techniques with high-spatio-temporal resolution, movement data were obtained from a population of vibrissae sampled at different locations on the mystacial pad in head-fixed rats isolated from the perturbing effects of contact. For a substantial proportion of the population of whisking movements sampled, the trajectories generated by a single whisker is most accurately described as occupying an expended two-dimensional space in which the A-P component predominates. However, the whisker system exhibits a considerable range of trajectory types, suggesting a high degree of movement flexibility. For each vibrissa position, it was possible to delineate a 'trajectory' domain -- that portion of the animal's whisking space which is scanned by the movements of that vibrissa during whisking. Since the 'domains' of adjacent whiskers in the same row tend to overlap, synchronized movements of a subset of whiskers could generate a set of overlapping somatosensory fields analogous to overlapping retinal receptive fields. The organization of such trajectory domains within the rats' whisking space could provide the spatial component of the spatio-temporal integration process required to extract information about environmental features from the inputs generated by its recursive whisking movements.     

Topography of rodent whisking--I. Two-dimensional monitoring of whisker movements

During 'active touch' the rodent whiskers scan the environment in a series of repetitive movements ('whisks') generating afferent signals which transform the spatial properties of objects into spatio-temporal patterns of neural activity. Based upon analyses carried out in a single movement plane, it has been generally assumed that these trajectories are essentially uni-dimensional, although more complex movements have been described in some rodents. The present study was designed to examine this assumption and to more precisely characterize whisking topography by monitoring whisking trajectories along both the antero-posterior and dorso-ventral axes. Using optoelectronic monitoring techniques with high-spatio-temporal resolution, movement data were obtained from a population of vibrissae sampled at different locations on the mystacial pad in head-fixed rats isolated from the perturbing effects of contact. For a substantial proportion of the population of whisking movements sampled, the trajectories generated by a single whisker is most accurately described as occupying an expended two-dimensional space in which the A-P component predominates. However, the whisker system exhibits a considerable range of trajectory types, suggesting a high degree of movement flexibility. For each vibrissa position, it was possible to delineate a 'trajectory' domain-that portion of the animal's whisking space which is scanned by the movements of that vibrissa during whisking. Since the 'domains' of adjacent whiskers in the same row tend to overlap, synchronized movements of a subset of whiskers could generate a set of overlapping somatosensory fields analogous to overlapping retinal receptive fields. The organization of such trajectory domains within the rats' whisking space could provide the spatial component of the spatio-temporal integration process required to extract information about environmental features from the inputs generated by its recursive whisking movements.     

Tactile Modulation of Whisking via the Brainstem Loop: Statechart Modeling and Experimental Validation

Rats repeatedly sweep their facial whiskers back and forth in order to explore their environment. Such explorative whisking appears to be driven by central pattern generators (CPGs) that operate independently of direct sensory feedback. Nevertheless, whisking can be modulated by sensory feedback, and it has been hypothesized that some of this modulation already occurs within the brainstem. However, the interaction between sensory feedback and CPG activity is poorly understood. Using the visual language of statecharts, a dynamic, bottom-up computerized model of the brainstem loop of the whisking system was built in order to investigate the interaction between sensory feedback and CPG activity during whisking behavior. As a benchmark, we used a previously quantified closed-loop phenomenon of the whisking system, touched-induced pump (TIP), which is thought to be mediated by the brainstem loop. First, we showed that TIPs depend on sensory feedback, by comparing TIP occurrence in intact rats with that in rats whose sensory nerve was experimentally cut. We then inspected several possible feedback mechanisms of TIPs using our model. The model ruled out all hypothesized mechanisms but one, which adequately simulated the corresponding motion observed in the rat. Results of the simulations suggest that TIPs are generated via sensory feedback that activates extrinsic retractor muscles in the mystacial pad. The model further predicted that in addition to the touching whisker, all whiskers found on the same side of the snout should exhibit a TIP. We present experimental results that confirm the predicted movements in behaving rats, establishing the validity of the hypothesized interaction between sensory feedback and CPG activity we suggest here for the generation of TIPs in the whisking system.     

Primary motor cortex reports efferent control of vibrissa motion on multiple timescales

Exploratory whisking in rat is an example of self-generated movement on multiple timescales, from slow variations in the envelope of whisking to the rapid sequence of muscle contractions during?a single whisk cycle. We find that, as a population, spike trains of single units in primary vibrissa motor cortex report the absolute angle of vibrissa position. This representation persists after sensory nerve transection, indicating an efferent source. About two-thirds of the units are modulated by slow variations in the envelope of whisking, while relatively few units report rapid changes in position within the whisk cycle. The combined results from this study and past measurements, which show that primary sensory cortex codes the whisking envelope as?a motor copy signal, imply that signals present in both sensory and motor cortices are necessary to compute angular coordinates based on vibrissa touch.     

Discriminative whisking in the head-fixed rat: optoelectronic monitoring during tactile detection and discrimination tasks

We compared whisking movement patterns during acquisition of tactile detection and object discrimination under conditions in which (a) head movements are excluded and (b) exposure to tactile discriminanda is confined to the large, moveable vibrissae (macrovibrissae). We used optoelectronic instrumentation to track the movements of an individual whisker with high spatio-temporal resolution and a testing paradigm, which allowed us to dissociate performance on an “indicator” response (lever pressing) from the rat's “observing” responses (discriminative whisking). We analyzed the relation between discrimination performance and whisking movement patterns in order to clarify the process by which the indicator response comes under the stimulus control of information acquired by the rat's whisking behavior. Whisking patterns over the course of task acquisition differed with task demands. Acquisition of the Detection task was correlated with modulation of only one whisking movement parameter - total number of whisks emitted, and more whisking was seen on trials in which the discriminandum was absent. Discrimination between a sphere and cube differing in size and texture was correlated with a reduction in whisk duration and protraction amplitude and with a shift towards higher whisking frequencies. Our findings confirm previous reports that acquisition of tactile discriminations involves modulation by the animal of both the amount and the type of whisking. In contrast with a previous report (Brecht et al., 1997), they indicate that rats can solve tactile object detection and discrimination tasks (a) using only the large, motile mystacial vibrissae (macrovibrissae) and (b) without engaging in head movements.We conclude that the functional contribution of the macrovibrissae will vary with the nature of the task and the conditions of testing.     

Whisking as a “voluntary” response: operant control of whisking parameters and effects of whisker denervation

The rat’s ability to vary its whisking “strategies” to meet the functional demands of a discriminative task suggests that whisking may be characterized as a “voluntary” behavior—an operant—and like other operants, should be modifiable by appropriate manipulations of response–reinforcer contingencies. To test this hypothesis we have used high-resolution, optoelectronic “real-time” recording procedures to monitor the movements of individual whiskers and reinforce specific movement parameters (amplitude, frequency). In one operant paradigm (N = 9) whisks with protractions above a specified amplitude were reinforced (Variable Interval 30?s) in the presence of a tone, but extinguished (EXT) in its absence. In a second paradigm (N = 3), rats were reinforced on two different VI schedules (VI-20s/VI-120s) signaled, respectively, by the presence or absence of the tone. Selective reinforcement of whisking movements maintained the behavior over many weeks of testing and brought it under stimulus and schedule control. Subjects in the first paradigm learned to increase responding in the presence of the tone and inhibit responding in its absence. In the second paradigm, subjects whisked at significantly different rates in the two stimulus conditions. Bilateral deafferentation of the whisker pad did not impair conditioned whisking or disrupt discrimination behavior. Our results confirm the hypothesis that rodent whisking has many of the properties of an operant response. The ability to bring whisking movement parameters under operant control should facilitate electrophysiological and lesion/behavioral studies of this widely used “model” sensorimotor system.     

One whisker whisking: unit recording during conditioned whisking in rats

Understanding of the functional neurobiology of the rodent whisker system would be advanced by neurobehavioral studies in awake, behaving animals that combine unit recording from structures at various levels of the system with quantitative characterization of the kinematics and temporal organization of whisking. Such studies require the solution of a number of methodological problems. These include: chronic recording procedures ensuring unit isolation, stability and maximum yield, monitoring and display of unit activity and whisker movements within the same (ms) timeframe and behavioral paradigms which bring whisking movement parameters under the control of the experimenter rather than the rat. Here we describe a head-fixed rodent preparation which makes possible chronic recording of unit activity in the awake, whisking rat, combined with real-time, high resolution monitoring of whisker and pad movements in two dimensions and under behavioral control. While the head-fixed "whisking" preparation has some inherent limitations, it may be used to address a number of important neurobehavioral problems. We suggest that it should contribute significantly to understanding the functional neurobiology of the whisker system.     

Whisker motor cortex ablation and whisker movement patterns

Previous studies, based on qualitative observations, reported that lesions of the whisker motor cortex produce no deficits in whisking behavior. We used high-resolution optoelectronic recording methods to compare the temporal organization and kinematics of whisker movements before and after unilateral lesions of whisker motor cortex in rats. We now report that while the lesion did not abolish whisking, it significantly disrupted whisking kinematics, coordination, and temporal organization. Lesioned animals showed significant increases in the velocity and amplitude of whisker protractions contralateral to the lesions, as well as a reduction in the synchrony of whisker movements on the two sides of the face. There was a marked shift in the distribution of whisking frequencies, with reduction of activity in the 5-7 Hz bandwidth and increased activity at < 2 Hz. Disruptions of the normal whisking pattern were evident on both sides of the face, and the magnitude of these effects was proportional to the extent of the cortical ablation. We suggest that the observed deficits reflect an imbalance in cortical inputs to a brainstem central pattern generator.     

Whisking as a "voluntary" response: operant control of whisking parameters and effects of whisker denervation

The rat's ability to vary its whisking "strategies" to meet the functional demands of a discriminative task suggests that whisking may be characterized as a "voluntary" behavior--an operant--and like other operants, should be modifiable by appropriate manipulations of response-reinforcer contingencies. To test this hypothesis we have used high-resolution, optoelectronic "real-time" recording procedures to monitor the movements of individual whiskers and reinforce specific movement parameters (amplitude, frequency). In one operant paradigm (N = 9) whisks with protractions above a specified amplitude were reinforced (Variable Interval 30 s) in the presence of a tone, but extinguished (EXT) in its absence. In a second paradigm (N = 3), rats were reinforced on two different VI schedules (VI-20s/VI-120s) signaled, respectively, by the presence or absence of the tone. Selective reinforcement of whisking movements maintained the behavior over many weeks of testing and brought it under stimulus and schedule control. Subjects in the first paradigm learned to increase responding in the presence of the tone and inhibit responding in its absence. In the second paradigm, subjects whisked at significantly different rates in the two stimulus conditions. Bilateral deafferentation of the whisker pad did not impair conditioned whisking or disrupt discrimination behavior. Our results confirm the hypothesis that rodent whisking has many of the properties of an operant response. The ability to bring whisking movement parameters under operant control should facilitate electrophysiological and lesion/behavioral studies of this widely used "model" sensorimotor system.     

Sniffing and whisking in rodents

Sniffing and whisking are two rhythmic orofacial motor activities that enable rodents to localize and track objects in their environment. They have related temporal dynamics, possibly as a result of both shared musculature and shared sensory tasks. Sniffing and whisking also constitute the overt expression of an animal's anticipation of a reward. Yet, the neuronal mechanisms that underlie the control of these behaviors have not been established. Here, we review the similarities between sniffing and whisking and suggest that such similarities indicate a mechanistic link between these two rhythmic exploratory behaviors.     

Responses of trigeminal ganglion neurons during natural whisking behaviors in the awake rat

Rats use their whiskers to locate and discriminate tactile features of their environment. Mechanoreceptors surrounding each whisker encode and transmit sensory information from the environment to the brain via afferents whose cell bodies lie in the trigeminal ganglion (Vg). These afferents are classified as rapidly (RA) or slowly (SA) adapting by their response to stimulation. The activity of these cells in the awake behaving rat is yet unknown. Therefore, we developed a method to chronically record Vg neurons during natural whisking behaviors and found that all cells exhibited (1) no neuronal activity when the whiskers were not in motion, (2) increased activity when the rat whisked, with activity correlated to whisk frequency, and (3) robust increases in activity when the whiskers contacted an object. Moreover, we observed distinct differences in the firing rates between RA and SA cells, suggesting that they encode distinct aspects of stimuli in the awake rat.