Knarik Bagdasarian

Layer-Specific Touch-Dependent Facilitation and Depression in the Somatosensory Cortex during Active Whisking

Brains adapt to new situations by retuning their neurons. The most common form of neuronal adaptation, typically observed with repetitive stimulations of passive sensory organs, is depression (responses gradually decrease until stabilized). We studied cortical adaptation when stimuli are acquired by active movements of the sensory organ. In anesthetized rats, artificial whisking was induced at 5 Hz, and activity of individual neurons in layers 2–5 was recorded during whisking in air (Whisking condition) and whisking against an object (Touch condition). Response strengths were assessed by spike counts. Input-layer responses (layers 4 and 5a) usually facilitated during the whisking train, whereas superficial responses (layer 2/3) usually depressed. In layers 2/3 and 4, but not 5a, responses were usually stronger during touch trials than during whisking in air. Facilitations were specific to the protraction phase; during retraction, responses depressed in all layers and conditions. These dynamic processes were accompanied by a slow positive wave of activity progressing from superficial to deeper layers and lasting for ∼1 s, during the transient phase of response. Our results indicate that, in the cortex, adaptation does not depend only on the level of activity or the frequency of its repetition but rather on the nature of the sensory information that is conveyed by that activity and on the processing layer. The input and laminar specificities observed here are consistent with the hypothesis that the paralemniscal layer 5a is involved in the processing of whisker motion, whereas the lemniscal barrels in layer 4 are involved in the processing of object identity.

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.

Temporal and spatial characteristics of vibrissa responses to motor commands.

A mechanistic description of the generation of whisker movements is essential for understanding the control of whisking and vibrissal active touch. We explore how facial-motoneuron spikes are translated, via an intrinsic muscle, to whisker movements. This is achieved by constructing, simulating, and analyzing a computational, biomechanical model of the motor plant, and by measuring spiking to movement transformations at small and large angles using high-precision whisker tracking in vivo. Our measurements revealed a supralinear summation of whisker protraction angles in response to consecutive motoneuron spikes with moderate interspike intervals (5 ms < Δt < 30 ms). This behavior is explained by a nonlinear transformation from intracellular changes in Ca2+ concentration to muscle force. Our model predicts the following spatial constraints: (1) Contraction of a single intrinsic muscle results in movement of its two attached whiskers with different amplitudes; the relative amplitudes depend on the resting angles and on the attachment location of the intrinsic muscle on the anterior whisker. Counterintuitively, for a certain range of resting angles, activation of a single intrinsic muscle can lead to a retraction of one of its two attached whiskers. (2) When a whisker is pulled by its two adjacent muscles with similar forces, the protraction amplitude depends only weakly on the resting angle. (3) Contractions of two adjacent muscles sums up linearly for small amplitudes and supralinearly for larger amplitudes. The model provides a direct translation from motoneuron spikes to whisker movements and can serve as a building block in closed-loop motor–sensory models of active touch.

On-going computation of whisking phase by mechanoreceptors

To attribute spatial meaning to sensory information, the state of the sensory organ must be represented in the nervous system. In the rodents vibrissal system, the whisking-cycle phase has been identified as a key coordinate, and phase-based representation of touch has been reported in the somatosensory cortex. Where and how phase is extracted in the ascending afferent pathways remains unknown. Using a closed-loop interface in anesthetized rats, we found that whisking phase is already encoded in a frequency- and amplitude-invariant manner by primary vibrissal afferents. We found that, for naturally constrained whisking dynamics, such invariant phase coding could be obtained by tuning each receptor to a restricted kinematic subspace. Invariant phase coding was preserved in the brainstem, where paralemniscal neurons filtered out the slowly evolving offset, whereas lemniscal neurons preserved it. These results demonstrate accurate, perceptually relevant, mechanically based processing at the sensor level.

Structure-function correlations of rat trigeminal primary neurons: Emphasis on club-like endings, a vibrissal mechanoreceptor

This study focuses on the structure and function of the primary sensory neurons that innervate vibrissal follicles in the rat. Both the peripheral and central terminations, as well as their firing properties were identified using intracellular labelling and recording in trigeminal ganglia in vivo. Fifty-one labelled neurons terminating peripherally, as club-like, Merkel, lanceolate, reticular or spiny endings were identified by their morphology. All neurons responded robustly to air puff stimulation applied to the vibrissal skin. Neurons with club-like endings responded with the highest firing rates; their peripheral processes rarely branched between the cell body and their terminal tips. The central branches of these neurons displayed abundant collaterals terminating within all trigeminal nuclei. Analyses of three-dimensional reconstructions reveal a palisade arrangement of club-like endings bound to the ringwulst by collagen fibers. Our morphological findings suggest that neurons with club-like endings sense mechanical aspects related to the movement of the ringwulst and convey this information to all trigeminal nuclei in the brainstem.

Muscular basis of whisker torsion in mice and rats

Whisking mammals move their whiskers in the rostrocaudal and dorsoventral directions with simultaneous rolling about their long axes (torsion). Whereas muscular control of the first two types of whisker movement was already established, the anatomic muscular substrate of the whisker torsion remains unclear. Specifically, it was not clear whether torsion is induced by asymmetrical operation of known muscles or by other largely unknown muscles. Here, we report that mystacial pads of newborn and adult rats and mice contain oblique intrinsic muscles (OMs) that connect diagonally adjacent vibrissa follicles. Each of the OMs is supplied by a cluster of motor end plates. In rows A and B, OMs connect the ventral part of the rostral follicle with the dorsal part of the caudal follicle. In rows C–E, in contrast, OMs connect the dorsal part of the rostral follicle to the ventral part of the caudal follicle. This inverse architecture is consistent with previous behavioral observations [Knutsen et al.: Neuron 59 (2008) 35–42]. In newborn mice, torsion occurred in irregular single twitches. In adult anesthetized rats, microelectrode mediated electrical stimulation of an individual OM that is coupled with two adjacent whiskers was sufficient to induce a unidirectional torsion of both whiskers. Torsional movement was associated with protracting movement, indicating that in the vibrissal system, like in the ocular system, torsional movement is mechanically coupled to horizontal and vertical movements. This study shows that torsional whisker rotation is mediated by specific OMs whose morphology and attachment sites determine rotation direction and mechanical coupling, and motor innervation determines rotation dynamics. Anat Rec, 300:1643–1653, 2017.

Morphological analysis of mechanoreceptors in the rat skin identified by intraganglionic injections of neuronal tracers

It is known that the regulation of baseline cerebral blood flow (CBF) is correlates with the metabolic demand of oxygen in brain tissue. However, the relationship between the increase in local CBF, induced by neuronal activation (evoked CBF), and oxygen demand in the activated brain area is still a disputable and controversial issue. In the present study, we investigated the effect of hypoxia on the baseline and evoked CBF using laser-Doppler flowmetry (LDF) to clarify the regulation mechanism of CBF in relation to the metabolic oxygen demand in rats. The effect of nitric oxide (NO) synthase inhibition on CBF regulation under hypoxia was also demonstrated using Nω-nitro-L-arginine (LNA). The CBF response to hind-paw stimulation was measured by laser-Doppler flowmetry. Physiological variables, such as heart rate, mean arterial blood pressure (MABP) and PaCO2 during hypoxia, were identical to those during normoxia. In the absence of LNA, hypoxia was accompanied by increase of the baseline CBF and the peak-amplitude of normalized evoked CBF relative to that during normoxia. The peak amplitude of normalized evoked CBF was 20.4±7.4% during hypoxia and 15.3±5.4% during normoxia (P < 0.05). The systemic administration of LNA (hypoxia with LNA) induced a significant enhancement of MABP and reduction of the heart rate in comparison with the values of both parameters, determined under normoxia (P < 0.01). The injection of LNA subjected to hypoxia showed the same baseline CBF as during normoxia, and there is a no significant difference in the normalized evoked CBF between hypoxia with LNA and normoxia. Field potential was constant for all experimental conditions. These results suggest that NO is involved in the enhancement of baseline and evoked CBF during hypoxia. NO inhibitor abolished the effect of hypoxia completely at the baseline level and evoked CBF; therefore, NO could be considered a major mediator of the relationship between hypoxia and evoked CBF response.