Arlette Kolta

Neurobiological Mechanisms Involved in Sleep Bruxism

Sleep bruxism (SB) is reported by 8% of the adult population and is mainly associated with rhythmic masticatory muscle activity (RMMA) characterized by repetitive jaw muscle contractions (3 bursts or more at a frequency of 1 Hz). The consequences of SB may include tooth destruction, jaw pain, headaches, or the limitation of mandibular movement, as well as tooth-grinding sounds that disrupt the sleep of bed partners. SB is probably an extreme manifestation of a masticatory muscle activity occurring during the sleep of most normal subjects, since RMMA is observed in 60% of normal sleepers in the absence of grinding sounds. The pathophysiology of SB is becoming clearer, and there is an abundance of evidence outlining the neurophysiology and neurochemistry of rhythmic jaw movements (RJM) in relation to chewing, swallowing, and breathing. The sleep literature provides much evidence describing the mechanisms involved in the reduction of muscle tone, from sleep onset to the atonia that characterizes rapid eye movement (REM) sleep. Several brainstem structures (e.g., reticular pontis oralis, pontis caudalis, parvocellularis) and neurochemicals (e.g., serotonin, dopamine, gamma aminobutyric acid [GABA], noradrenaline) are involved in both the genesis of RJM and the modulation of muscle tone during sleep. It remains unknown why a high percentage of normal subjects present RMMA during sleep and why this activity is three times more frequent and higher in amplitude in SB patients. It is also unclear why RMMA during sleep is characterized by co-activation of both jaw-opening and jaw-closing muscles instead of the alternating jaw-opening and jaw-closing muscle activity pattern typical of chewing. The final section of this review proposes that RMMA during sleep has a role in lubricating the upper alimentary tract and increasing airway patency. The review concludes with an outline of questions for future research.

Generation of the Central Masticatory Pattern and Its Modification by Sensory Feedback

Mammalian mastication results from the interaction of an intrinsic rhythmical neural pattern and sensory feedback generated by the interaction of the effecter system (muscles, bones, joints, teeth, soft tissues) with food. The main variables that explain variation in the pattern of human mastication are the subjects themselves, their age, the type of food being eaten, and time during a sequence of movements. The intrinsic pattern of mastication is generated by a central pattern generator (CPG) located in the pons and medulla. The output of the CPG is modified by inputs that descend from higher centers of the brain and by feedback from sensory receptors. Intraoral touch receptors, muscle spindles in the jaw-closing muscles, and specialized mechanoreceptors in the periodontal ligament have especially powerful effects on movement parameters.

Brainstem mechanisms underlying feeding behaviors

The essential elements controlling trigeminal motoneurons during feeding lie between the trigeminal and facial motor nuclei. These include populations of neurons in the medial reticular formation and pre-motoneurons in the lateral brainstem that reorganize to generate various patterns. Orofacial sensory feedback, antidromic firing in spindle afferents and intrinsic properties of motoneurons also contribute to the final masticatory motor output.

Identification of brainstem interneurons projecting to the trigeminal motor nucleus and adjacent structures in the rabbit.

Neurons of several nuclei within the medial pontomedullar reticular formation are active during mastication, but their relationship with other elements of the pattern generating circuits have never been clearly defined. In this paper, we have studied the connection of this area with the trigeminal motor nucleus and with pools of last-order interneurons of the lateral brainstem. Retrograde tracing techniques were used in combination with immunohistochemistry to define populations of glutamatergic and GABAergic neurons. Injections of tracer into the Vth motor nucleus marked neurons in several trigeminal nuclei including the ipsilateral mesencephalic nucleus, the contralateral Vth motor nucleus, the dorsal cap of the main sensory nucleus and the rostral divisions of the spinal nucleus bilaterally. Many last-order interneurons formed a bilateral lateral band running caudally from Regio h (the zone surrounding the Vth motor nucleus), through the parvocellular reticular formation and Vth spinal caudal nucleus. Injections of tracer into Regio h, an area rich in last-order interneurons, marked, in addition to the areas listed above, a large number of neurons in the medial reticular formation bilaterally. The major difference between injection sites was that most neurons projecting to the Vth motor nucleus were located laterally, whereas most of those projecting to Regio h were found medially. Both populations contained glutamatergic and GABAergic neurons intermingled. Our results indicate that neurons of the medial reticular formation that are active during mastication influence Vth motoneurons output via relays in Regio h and other adjacent nuclei.

Neurons of the trigeminal main sensory nucleus participate in the generation of rhythmic motor patterns

The trigeminal principal sensory nucleus (NVsnpr) contains both trigemino‐thalamic neurons and interneurons projecting to the reticular formation and brainstem motor nuclei. Here we describe the inputs and patterns of firing of NVsnpr neurons during fictive mastication in anaesthetized and paralysed rabbits to determine the role that NVsnpr may play in patterning mastication. Of the 272 neurons recorded in NVsnpr, 107 changed their firing patterns during repetitive stimulation of the left or right sensorimotor cortex to induce fictive mastication. Thirty increased their firing tonically. Seventy‐seven became rhythmically active, but only 31 fired in phase with mastication. The others discharged in bursts at more than twice the frequency of trigeminal motoneurons. Most rhythmic masticatory neurons were concentrated in the dorsal part, and those which fired during the jaw closing phase of the cycle were confined to the anterior pole of the nucleus. Most of these cells had inputs from muscle spindle afferents, whereas most of those firing during jaw opening had inputs from periodontal receptors. Non‐masticatory rhythmical neurons had receptive fields on the lips and face. The majority of rhythmical masticatory units were modulated during fictive mastication evoked by both the left and right cortices and only four changed their phase of firing when switching from one cortex to the other. When coupled with the finding that NVsnpr neurons exhibit spontaneous bursting in vitro[Sandler et al. (1998) Neuroscience, 83, 891], the results described here suggest that neurons of dorsal NVsnpr may form the core of the central pattern generator for mastication.

Generation of the masticatory central pattern and its modulation by sensory feedback

The basic pattern of rhythmic jaw movements produced during mastication is generated by a neuronal network located in the brainstem and referred to as the masticatory central pattern generator (CPG). This network composed of neurons mostly associated to the trigeminal system is found between the rostral borders of the trigeminal motor nucleus and facial nucleus. This review summarizes current knowledge on the anatomical organization, the development, the connectivity and the cellular properties of these trigeminal circuits in relation to mastication. Emphasis is put on a population of rhythmogenic neurons in the dorsal part of the trigeminal sensory nucleus. These neurons have intrinsic bursting capabilities, supported by a persistent Na(+) current (I(NaP)), which are enhanced when the extracellular concentration of Ca(2+) diminishes. Presented evidence suggest that the Ca(2+) dependency of this current combined with its voltage-dependency could provide a mechanism for cortical and sensory afferent inputs to the nucleus to interact with the rhythmogenic properties of its neurons to adjust and adapt the rhythmic output. Astrocytes are postulated to contribute to this process by modulating the extracellular Ca(2+) concentration and a model is proposed to explain how functional microdomains defined by the boundaries of astrocytic syncitia may form under the influence of incoming inputs.

An immunocytochemical and autoradiographic investigation of the serotoninergic innervation of trigeminal mesencephalic and motor nuclei in the rabbit

The results of a previous experiment suggest that the cell bodies of many jaw closing muscle spindle afferents in the trigeminal mesencephalic nucleus of the rabbit are phasically inhibited during fictive mastication. The aim of this study was to investigate one possible neurotransmitter system that could be involved in this modulation, serotonin, by use of receptor autoradiography techniques and immunofluorescence combined with retrograde labelling of masseteric spindle afferents and motoneurons. A second objective was to compare the serotonin innervation of neurons in the trigeminal mesencephalic nucleus with that of masseteric motoneurons. Serotoninergic fibres were seen surrounding labelled masseteric spindle afferents, as well as unlabelled neurons, in the trigeminal mesencephalic nucleus. These fibres were close to the cell bodies and sometimes to the axon hillocks of the neurons. Although it has been reported that many neurons of the trigeminal nucleus are multipolar in some species, none of the labelled spindle afferent in this study had more than one process. Throughout the motor trigeminal nucleus, serotonin fibres were found in close proximity with cell bodies and with the proximal portions of axons and dendrites of labelled and unlabelled motoneurons. Serotonin fibres were also seen adjacent to cell bodies and processes of efferent neurons in cell group k. Autoradiography with several tritiated ligands was used to reveal the presence of receptors for serotonin as well as its uptake sites. Only serotonin2 receptors were found to be abundant in the trigeminal mesencephalic nucleus. The motor nucleus and cell group k contained serotonin2 and serotonin3 receptors, as well as serotonin uptake sites. Serotonin1A receptors appear to be absent from both nuclei. The findings suggest that release of serotonin from fibres in close proximity to trigeminal primary afferent somata could modify the transmission of action potentials from muscle spindle receptors during mastication through an action on serotonin2 receptors. In the motor nucleus and cell group k, serotonin may alter neuronal properties through actions on at least two receptor subtypes (serotonin2 and serotonin3).

An astrocyte-dependent mechanism for neuronal rhythmogenesis.

Communication between neurons rests on their capacity to change their firing pattern to encode different messages. For several vital functions, such as respiration and mastication, neurons need to generate a rhythmic firing pattern. Here we show in the rat trigeminal sensori-motor circuit for mastication that this ability depends on regulation of the extracellular Ca2+ concentration ([Ca2+]e) by astrocytes. In this circuit, astrocytes respond to sensory stimuli that induce neuronal rhythmic activity, and their blockade with a Ca2+ chelator prevents neurons from generating a rhythmic bursting pattern. This ability is restored by adding S100β, an astrocytic Ca2+-binding protein, to the extracellular space, while application of an anti-S100β antibody prevents generation of rhythmic activity. These results indicate that astrocytes regulate a fundamental neuronal property: the capacity to change firing pattern. These findings may have broad implications for many other neural networks whose functions depend on the generation of rhythmic activity.

Evidence for functional compartmentalization of trigeminal muscle spindle afferents during fictive mastication in the rabbit.

Primary afferent neurons innervating muscle spindles in jaw‐closing muscles have cell bodies in the trigeminal mesencephalic nucleus (NVmes) that are electrically coupled and receive synapses. Each stem axon gives rise to a peripheral branch and a descending central branch. It was previously shown that some spikes generated by constant muscle stretch fail to enter the soma during fictive mastication. The present study examines whether the central axon is similarly controlled. These axons were functionally identified in anaesthetized and paralysed rabbits, and tonic afferent firing was elicited by muscle stretch. For the purpose of comparison, responses were recorded extracellularly both from the somatic region and from the central axon in the lateral brainstem. Two types of fictive masticatory movement patterns were induced by repetitive stimulation of the masticatory cortex and monitored from the trigeminal motor nucleus. Field potentials generated by spike‐triggered averaging of action potentials from the spindle afferents were employed to determine their postsynaptic effects on jaw‐closing motoneurons. Tonic firing of 32% NVmes units was inhibited during the jaw‐opening phase, but spike frequency during closing was almost equal to the control rate during both types of fictive mastication. A similar inhibition occurred during opening in 83% of the units recorded along the central branch. However, firing frequency in these was significantly increased during closing in 94%, probably because of the addition of antidromic action potentials generated by presynaptic depolarization of terminals of the central branch. These additional spikes do not reach the soma, but do appear to excite motoneurons. The data also show that the duration and/or frequency of firing during the bursts varied from one pattern of fictive mastication to another. We conclude that the central axons of trigeminal muscle spindle afferents are functionally decoupled from their stem axons during the jaw‐closing phase of mastication. During this phase, it appears that antidromic impulses in the central axons provide one of the inputs from the masticatory central pattern generator (CPG) to trigeminal motoneurons.

Do muscle-spindle afferent act as interneurons during mastication?

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