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Neuronal activity in the putamen and the globus pallidus of rabbit during mastication
Neuroscience Research 39 (2001) 11 – 19 www.elsevier.com/locate/neures
Neuronal activity in the putamen and the globus pallidus of rabbit during mastication Yuji Masuda *, Takafumi Kato, Osamu Hidaka 1, Ryuji Matsuo 2, Tomio Inoue 3, Koichi Iwata, Toshifumi Morimoto Department of Oral Physiology, Faculty of Dentistry, Osaka Uni6ersity, 1 -8 Yamadaoka, Suita, Osaka 565 -0871, Japan Received 6 July 2000; accepted 8 August 2000
Abstract The pattern of jaw movements is changed during a masticatory sequence from ingestion of food to its deglutition. The masticatory sequence is divided into three distinct stages in the rabbit. However, the neural mechanism involved in the alteration of the masticatory stages is still unknown. This study was designed to determine whether neuronal activity in the putamen and globus pallidus is related to the alteration of the masticatory stages. Fifty-three percent of the recorded neurons showed significant alterations of activity during mastication. Of these neurons, 16% changed their firing frequency throughout the masticatory sequence (sequence-related neurons) and 84% changed their firing frequency with the transition of the masticatory stages (stage-related neurons). The stage-related neurons were classified into two groups based on their neuronal activity patterns observed during mastication, i.e. simple type and complex type. The former are the neurons that were either facilitated or inhibited once during mastication, and the latter are those showing the facilitation or inhibition twice or more during mastication. Complex-type neurons were observed more frequently in the globus pallidus than in the putamen. These results suggest that the basal ganglia is involved in mastication and may related to the transition between the masticatory stages. © 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. Keywords: Mastication; Jaw movement; Putamen; Globus pallidus; Neuronal activity; Sequence; Rabbit
1. Introduction The masticatory sequence is a whole set of movements from ingestion to swallowing. It is made up of masticatory cycles that change in movement pattern as the food is gathered, moved backward to the molar teeth, then broken down and prepared for swallowing (Lund, 1991). The masticatory sequence can be divided into three distinct stages (stage I, IIa, IIb) in the rabbit based on the form of the jaw movements (Morimoto et al., 1985; Schwartz et al., 1989). The food is transported * Corresponding author. Tel.: +81-6-6879-2882; fax: + 81-6-68792885. E-mail address: [email protected] (Y. Masuda). 1 Department of Orthodontics and Dentofacial Orthopedics, Osaka University Faculty of Dentistry, Suita, Osaka 565-0871, Japan. 2 Department of Oral Physiology, Okayama University Dental School, Okayama, Okayama 700-8525, Japan. 3 Department of Oral Physiology, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555 Japan.
back to the molar teeth during stage I and ground up during stage II. The transition from stage I to II occurs abruptly. It is now generally accepted that the motor command for the basic pattern of rhythmical oral-facial movements during chewing is generated by a neuronal population in the brain stem (central pattern generator) (Nakamura and Katakura, 1995 for review). Sensory input from a variety of intraoral, joint, and muscle receptors interact with the central control system in the brain stem to adapt the program of chewing movements to the characteristics of the food (Morimoto et al., 1989; Hidaka et al., 1997). Therefore, the jaw movements for chewing have been called semi-automatic movements. However, it is still unclear what neural mechanism is involved in the transition from stage I, in which the animal manipulates the food and leads to the semi-automatic chewing movements, to stage II. Many investigations have demonstrated that feeding deficits are caused by lesions of the striatum or globus
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pallidus (GP), or destruction of nigrostriatal dopaminergic neurons (Zigmond and Stricker, 1972; Labuszewski et al., 1981; Palfai et al., 1984; Pisa, 1988; Pisa and Schranz, 1988; Jicha and Salamone, 1991; Szczypka et al., 1999). These kinds of feeding deficits have been attributed to sensory – motor impairment and/or a loss of the motivation to eat. Some investigations have discussed impairment of oro-facial movements as a potential mechanism of these feeding deficits. Pisa and Schranz (1988) have found that lesions of the ventrolateral striatum impaired the reaching movements of the tongue. Moreover, Pisa (1988) reported that lesions of the lateral striatum impaired motor performance during feeding, and lesions of the ventral region especially influenced mouth – tongue movements. On the other hand, Labuszewski et al. (1981) observed that during the early phase of recovery of feeding behavior after GP lesion, rats spilled large quantities of food while chewing. These findings showed that the basal ganglia might play a role in the control of masticatory movements, including jaw and tongue and other orofacial movements. Many studies have provided evidence for the hypothesis that the basal ganglia is involved in the sequence of actions of learned hand movement (Kimura, 1990; Kimura et al., 1992; Kermadi and Joseph, 1995; Matsumoto et al., 1999), trained head movement (Gardiner and Kitai, 1992), and grooming (Berridge and Whishaw, 1992; Cromwell and Berridge, 1996). Assuming that mastication, consisting of food transport, chewing and swallowing, was a sequenced action, we reasoned that the basal ganglia might be involved in the progress of mastication. In this study, therefore, in order to investigate the relationship between the masticatory movements and neuronal activity of the basal ganglia in the awake rabbit, we examined whether neurons in the putamen (PUT) and GP alter their firing rates in relation to the masticatory movements and also whether the alteration of the firing frequency in the PUT and GP neurons related to the progress of mastication.
2. Materials and methods Twelve male rabbits (2.3 – 3.0 kg), in whom the jaw movement patterns during the masticatory sequence had been well analyzed (Morimoto et al., 1985; Schwartz et al., 1989), were used. All the surgical procedures were reviewed and approved by the Osaka University Faculty of Dentistry Intramural Animal Care and Use Committee. The animals were anesthetized with pentobarbital sodium (20 mg/kg) and ketamine HCl (20 mg/kg) via an ear vein. Supplementary doses of anesthetic were given when necessary. During surgery, anesthesia was maintained at such a
level that no reflexive jaw opening resulted from pinching the facial skin. The procedures for attachment of a phototransistor array to the mandible for tracing jaw movements and the insertion of pairs of enamel-coated copper wires (150 mm diameter, 5 mm spacing, 1.5 mm tip bared) into the left masseter and digastric muscles for electromyogram (EMG) recording were the same as those reported elsewhere (Inoue et al., 1989). A stainless steel cylinder for a modified Evarts type of micromanipulator (MO-95, Narishige-Kagaku, Tokyo, Japan) was fixed at the right parietal area for recording the neuronal activity in the basal ganglia. The rabbits were maintained in good health by veterinary care throughout the experimental period. Recordings were started at least 4 days after the surgery and lasted several days (each daily session lasted about 2 h). During the experiments, the rabbit’s head was supported in a frame by means of skull screws. Rabbits readily accepted this type of fixation and chewed food without apparent disturbance. Neuronal activity was recorded simultaneously with EMG and jaw movements as described elsewhere (Masuda et al., 1997). A glass-coated metal microelectrode with an impedance of 1–3 MV at 1 kHz was inserted vertically through the right cerebral cortex towards the basal ganglia. The electrode penetrations were located between 0 and 1 mm anterior to bregma and between 5.0 and 7.0 mm lateral to the midline. Four pieces of carrot, cut as quadrangular prisms (3.5× 3.5× 10 mm), were inserted at one time into the rabbit’s mouth. Once we had succeeded in recording the neuronal activity during mastication in a given rabbit, the recording sites were marked by passing a negative current of 30 mA through the recording electrode for 10 s under deep anesthesia at the end of experiment. The rabbit was perfused with saline followed by formalin (10%). In short, recordings and markings were performed by means of a single electrode in each rabbit. The recording sites were later identified on 50 mm sections of the brain stained with cresyl violet. The data were stored on a digital tape recorder (PC-208, Sony-Magnescale, Tokyo, Japan) and spike discrimination and data processing were later performed using a Cambridge Electronics 1401 data acquisition board and Spike2 analysis package (Cambridge Electronic Design, Cambridge, UK). For each neuron, the activity was analyzed from 6 s before the onset of jaw opening in the first cycle during mastication to the end of the masticatory sequence. To determine the change in activity during mastication, peri-event histograms of the entire masticatory sequence for at least three trials were made using 100 ms bins triggered by the onset of the first jaw opening. From each histogram, the mean number of spikes and standard deviation (S.D.) of spontaneous unit discharge were calculated for a 1.5 s period during the resting condition (commonly 4 s preceding the onset of mastication).
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A change in activity was determined to have occurred if, considering 100 ms bin histograms, the number of spikes increased or decreased by at least 2 S.D. of the mean of the spontaneous unit discharge, and lasted for at least 300 ms (3 bins). The neuronal activity, if a change in activity during mastication was detected, was examined to determine whether its change related to the transition between the masticatory stages, using the peri-event histograms triggered by the point of transition from stage I to II (at least three trials). We defined neurons, which showed the same alterations before and after the point of transition from stage I to II, as sequence-related neuron, and neurons, which showed different neuronal activity between stage I and II, as stage-related neuron. Stage IIa and IIb have been regarded as the molar chewing stage and the swallowing preparatory stage, respectively. However, a later study demonstrated that swallowing occurred during the chewing stage (McFarland and Lund, 1993). In this study, we did not examine the transition from stage IIa to IIb because of the slight difference of jaw movement pattern observed during the stages and the unclear distinction of the functional role of these two stages.
3. Results The activity of a total of 93 single neurons recorded in the PUT (n=34) and GP (n =59) of the 12 awake rabbits was successfully studied throughout the whole masticatory sequence. Spontaneous activity was observed in all of the 93 recorded neurons. The mean frequency of spontaneous activity of the neurons in the PUT (26.39 18.0 Hz; mean9 S.D.) was significantly (U-test, P B0.01) lower than that in the GP (41.49 17.0 Hz) (Fig. 1).
Fig. 1. A histogram of the mean frequency of spontaneous activity in the recorded neurons from the PUT (solid column) and the GP (open column). Note: the mean frequency of spontaneous activity of the neurons in PUT was significantly (U-test, PB 0.01) lower than that in the GP.
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Of the 34 PUT neurons, 20 showed alterations of activity above and/or below 2 S.D. of the mean frequency of spontaneous activity during mastication, and of the 59 GP neurons, 29 had similar alterations in activity. The frequency of occurrence of these neurons in the PUT was not significantly different from that found in GP (Fisher’s exact test, P \ 0.05). Of the 20 PUT neurons and the 29 GP neurons which changed firing frequency during mastication, 17 PUT neurons and 24 GP neurons showed this alteration at the transition from stage I to II (stage-related neurons). The remaining 3 PUT neurons and 5 GP neurons changed firing frequency throughout the mastication sequence (sequence-related neurons). The ratio of the stage-related neurons in the PUT was not significantly different from that in the GP (Fisher’s exact test, P\ 0.05).
3.1. Sequence-related neurons Fig. 2 illustrates an example of neuronal activity obtained from the GP (Fig. 2D), showing the increments of firing rates throughout the masticatory sequence. The masticatory sequence was confirmed to be divided into three stages (I, IIa and IIb) as reported previously (Morimoto et al., 1985), and the movement traces on the frontal plane during each stage are shown in Fig. 2A. When the food materials were inserted, the touch of the syringe to the lip induced the first jaw opening and commenced stage I. The rabbit accepted the food and transferred it to the molar region at stage I during which jaw movements consisted of irregular repetitive simple open-close movements with small lateral movements. During stage II, the rabbit crushed and ground foods with regular jaw movements. The firing rate of this neuron increased at the onset of the mastication, and this increment lasted to the end of masticatory sequence. In stage II, firing frequency did not relate to the jaw opening or jaw closing. Rather, the alteration of firing frequency depended on the change in masticatory sequence, not on the masticatory cycle (Fig. 2B and C). All neurons related to mastication, which were recorded from the PUT and the GP in this study, altered their firing frequency according to the change in masticatory stages or sequence. Fig. 3 shows the neuronal activity of a sequence-related neuron recorded from the PUT (Fig. 3B) during ten successive trials of mastication. This neuron increased its firing frequency throughout the masticatory sequence on every one of the ten trials. The change in firing frequency of all the recorded neurons was consist on every trial of mastication like neuronal activity shown in Fig. 3. In this study, to determine the change in activity during mastication, peri-event histograms of the entire masticatory sequence for at least three trials were used. All of the three sequence-related neurons recorded from the PUT showed an increase of activity through-
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firing rate disappeared at the point of transition from stage I to II (Fig. 4B). Stage-related neurons were classified into two groups based on their neuronal activity patterns observed during mastication. We defined an event as a period in which the firing rate was continually out of the range of the mean spontaneous firing rate (mean92 S.D.). Neurons showing one event throughout the masticatory sequence were named simple-type neurons (Fig. 5), and those showing two or more events were termed complex-type neurons (Fig. 6). Most of the stage-related PUT neurons (15/17) were simple-type neurons, whereas 58% of the stage-related GP neurons (14/24) were simple-type neurons. The remaining 42% of the GP neurons (10/24) were regarded as the complex type.
Fig. 2. The activity of a sequence-related neuron from the GP. (A) The modulation of neuronal activity in the GP throughout a masticatory sequence. The upper most and the second records show the firing rate and the spike record, respectively. Ver and Hor: vertical and horizontal jaw movements. Mass and Dig: EMGs of the masseter and digastric muscles. At the bottom: jaw movements on the frontal plane in stage I, IIa and IIb. Small arrows indicate the direction of jaw movements. (B) Expanded records of the hatched parts in A. (C) Phase relationship of unit discharges to jaw movement cycles. Averaged jaw movements of ten masticatory cycles (top two records) and histogram of neuronal activity triggered by the jaw-closed position. (D) Recorded site of this neuron is shown by *. PUT, putamen. GP, globus pallidus. IC, internal capsule. AC, anterior commissure.
out mastication. Of the five sequence-related neurons from the GP, four neurons has an increment in firing rate and one neuron had a decrement of firing rate throughout mastication.
3.2. Stage-related neurons Fig. 4 shows the activity of a stage-related neuron located in the PUT during three masticatory trials aligned by the onset of the first jaw opening (A) and by the point of transition from stage I to II (B). This neuron showed an increase in firing rate preceding the onset of mastication (Fig. 4A). This increment of the
Fig. 3. The activity of a sequence-related neuron from the PUT. (A) The activity of a PUT neuron during ten trials of mastication. Traces have been aligned by the onset of the first jaw opening. The horizontal dotted line on the histogram indicates the mean + 2 S.D. of spontaneous firing frequency. (B) Recorded site of this neuron is shown by *. PUT, putamen. GP, globus pallidus. IC, internal capsule. AC, anterior commissure. (C) 40 superimposed traces of the neuron’s wave form.
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Fig. 4. The activity of a stage-related neuron from the PUT during three trials of mastication. The traces have been aligned by the onset of the first jaw opening (A) and the point of the transition from stage I to II (B). The horizontal dotted line on the histograms indicate the mean +2 S.D. of spontaneous firing frequency.
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Fig. 5. The activity of simple-type neurons from the PUT (A) and the GP (B) during three trials of mastication. The traces have been aligned by the onset of the first jaw opening. The upper and lower horizontal dotted line on the histograms indicate the mean +2 S.D. and mean−2 S.D. of spontaneous firing frequency, respectively.
3.2.1. Simple-type neurons Fourteen of 15 PUT simple-type neurons showed an alteration of firing only during stage I; 11 showed an increase (Fig. 5A) whereas three showed a decrease. They did not change their firing frequency in stage II. One of 15 simple-type neurons increased only during stage II. Thirteen of the 14 GP simple-type neurons changed their firing rate only during stage I. All of their alterations (11: increase, 2: decrease) during stage I did not last to stage II (Fig. 5B). Only one simple-type GP neuron, which did not change its firing frequency during stage I, did decrease during stage II. 3.2.2. Complex-type neurons Of the PUT stage-related neurons, two neurons were regarded as complex-type neurons. One showed an increase during stage I and a decrease during stage II. Another neuron showed a decrease during stage I and an increase during stage II. Five of the ten GP complex-type neurons, showed both an increase and decrease during a masticatory sequence. Two of them showed an increase during stage I and a decrease during stage II, whereas three of them showed a decrease during stage I and an increase during stage II (Fig. 6A). Four of the ten GP complextype neurons showed a decrease during stage I and a
Fig. 6. The activity of two kinds of complex-type neurons from the GP during four trials of mastication. The traces have been aligned by the point of the transition from stage I to II. The upper and lower horizontal dotted line on the histograms indicate the mean + 2 S.D. and mean−2 S.D. of spontaneous firing frequency, respectively.
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4.1. Spontaneous acti6ity
Fig. 7. The location of neurons on representative histological sections at the level of 1 mm (left) and 0 mm (right) anterior to bregma that changed their firing frequency throughout mastication, the location of the simple-type and complex-type neurons, and the location of neurons who’s activity was not related to mastication. Triangle, open circles, filled circles and crosses indicate neurons changed firing frequency throughout mastication, simple-type neurons, complex-type neurons and neurons not related to mastication, respectively. PUT, putamen. CD, caudate nucleus. GP, globus pallidus. IC, internal capsule. EC, external capsule. AC, anterior commissure.
decrease during stage II after the firing rate came back to the range of the mean spontaneous firing rate (mean9 2 S.D.) at the transition between stages (Fig. 6B). The remaining neuron, whose firing rate decreased immediately before the onset of the first jaw opening, showed an increase during stage I without alteration during stage II.
3.3. Location of recorded neurons Fig. 7 shows the recording site of neurons that changed firing frequency throughout mastication, both simple-type and complex-type neurons, and also neurons not related to mastication which are plotted collectively in drawings of the representative histological sections at the level of 0 and 1 mm anterior to bregma. Neurons related and unrelated to mastication were found throughout the PUT and GP. Furthermore, there were no preferential locations of simple-type or complex-type neurons in the PUT and GP.
4. Discussion The present study has shown that about 50% of the PUT and the GP neurons altered their firing frequency in relation to mastication in correspondence with changes in masticatory stages or masticatory sequence but not within masticatory cycles. These findings suggest that the basal ganglia may be involved in the adaptation of the masticatory process based on the circumstances in the mouth.
For every neuron we defined the mean frequency for the 1.5 s period preceding the onset of mastication as the mean frequency of spontaneous activity. The mean frequency of spontaneous activity of the neurons in the PUT was significantly lower than that in the GP (Fig. 1). Although the difference between the PUT and the GP was consistent with the findings of many earlier investigations, the levels of activity found in the present study differed considerably from those observed in other species (DeLong, 1972; Schneider et al., 1982; DeLong et al., 1985; Kimura, 1990; Gardiner and Kitai, 1992; Cheuruel et al., 1994). Based on many investigations, firing frequency of neurons in the striatum is known to be very low (less than 10 Hz), while that in the GP is very high (50–100 Hz). In the monkey, it was observed that in the external segment of GP (Gpe), which is equivalent to the GP in the rabbit, neurons were divided into two groups on the basis of their baseline firing frequency (1) ones with low spontaneous activity of around 8 spikes per s, (2) ones with high activity of around 80 spikes per s (Mink and Thach, 1991). However, in another study, very low levels of activity were also described (Iansek and Porter, 1980). In our study, GP neurons in rabbits could not be divided into two groups according to the histogram of the spontaneous activity. Rather, the spontaneous activity of GP neurons showed a wide range of levels. The study of Jaeger et al. (1993) reported the mean baseline firing rate of GPe neurons was around 40 spikes per s, which is similar to our data. Although the PUT neurons in this study could be divided into two groups according to mean spontaneous firing frequency, as well as the PUT neurons in the primate, the firing frequency during the resting condition of the PUT neurons in our study was higher than that in previous studies. These differences in the firing rate could be related to a sample bias, and/or species differences. Furthermore, it may be due to differences in the experimental conditions. Our experiment did not require the performance of a task. Rather, the experimenter just gave food to the animals. Under our experimental conditions, the fact that the animals were always ready to perform the ingestion behavior may have modulated the firing frequency of neurons throughout the experiments.
4.2. Acti6ity patterns related to mastication There are a few studies that examined the neural activity of the basal ganglia in relation to the masticatory sequence. Nishino et al. (1991), who recorded neural activity from the caudate nucleus, GP, and the substantia nigra pars reticulata during operant feeding behavior in the monkey, found that some neurons
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altered their firing frequency during the ingestion of solid-food reward. The majority of these responses consisted of long-lasting inhibition throughout ingestion, as with the sequence-related neurons in this study. The increase of the firing rates of PUT neurons after the delivery of a reward (apple juice) were examined by Apicella et al. (1991). Those responses showed a short or long single peak of increased activity that was temporally unrelated to EMG activity in the masseter muscle. Although jaw movement patterns were not examined in that study, our results are consistent with their observation that neuronal responses did not relate to each masticatory cycle. It has been demonstrated that the rhythm of the masticatory cycles is formed in the brain stem (Nozaki et al., 1986a,b). Although the jaw movements were rhythmic throughout the masticatory sequence, the pattern of jaw movements, the sensitivity of the afferent from the trigeminal area and the aim of the jaw movements are different between the stages (Morimoto et al., 1985; Schwartz et al., 1989; Masuda et al., 1997). Therefore, the jaw movements in each stage appeared to be distinct movements from each other. However, it is unclear which neuronal mechanism controls the alteration of jaw movements associated with masticatory progress. The present results show that the discharge pattern in some of the neurons recorded from the basal ganglia related to the transition between these stages, indicating that the basal ganglia might play an important role in the transition between stages. Many investigations have suggested that the basal ganglia has a specific role in the construction and execution of motor plans (Hikosaka et al., 1989a,b,c; Kermadi and Joseph, 1995; see review Graybiel, 1995). The PUT is thought to be involved in the initiation of movement by selecting a particular learned movement associated with contextual sensory cues (Kimura, 1990). The basal ganglia may have a similar relationship to mastication. The stage-related neurons exhibited a variety of activity patterns. The neurons were classified into two types (simple and complex type) on the basis of their activity patterns throughout the masticatory sequence. Both types of neurons were related to the transition between stages. Most of the PUT neurons related to mastication were simple-type neurons, whereas 42% of the GP neurons were complex-type neurons. Anatomical data indicate that the GP receives input from the striatum and the input has convergence (Flaherty and Graybiel, 1993). If it is plausible that complex-type neurons are linked to the transition of the stages more strongly than simple-type neurons, the finding that complex-type neurons were observed more frequently in the GP than in the PUT suggests that the neural network in the basal ganglia may provide the information to emphasize the transition of the stages. It is reported that some neurons in the cortical
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masticatory area activated throughout mastication are not related to the masticatory cycles (Lund and Lamarre, 1974), and change firing frequency depending on the alteration of the stages (Masuda et al., 1995). On the other hand, there are neurons in the substantia nigra that are tonically activated during drinking behavior (Mora et al., 1977). The PUT has projections from both the cerebral cortex and substantia nigra. The discharge pattern of the PUT neurons recorded in this study may be influenced by the neural activity of these two areas.
4.3. Location of the neurons related to mastication In this study, we obtained data from the PUT and GP rostro-caudally at the level of the anterior commissure (the electrode penetrations were located between 0 and 1 mm anterior to bregma and between 5.0 and 7.0 mm lateral to the midline). In the rabbit, there has been no study of the relationship between the basal ganglia and oral motor behavior. In primates, somatotopic organization was clearly evident with respect to both the sensorimotor response properties of PUT neurons and the anatomic foci of microstimulation-evoked movements (Alexander and DeLong, 1985). Representation of orofacial structures was confined to the ventral portion of the PUT. In the rabbit, the neurons recorded in this study, which changed their activity during mastication, were located throughout the PUT and the GP in certain rostorocaudal levels. The somatotopic organization found in the somatosensory cortex in the rabbit indicates that the orofacial sensory projection area occupied most of somatosensory cortex (Gould, 1986). Further, the cortical masticatory area, in which electrical stimulation induced rhythmical jaw movements, also occupied large area of frontal cortex in the rabbits (Lund et al., 1984; Liu et al., 1993). This means that in rabbits the orofacial region was functionally more important for manipulation than the other body parts (e.g. forepaw, forelimb etc.). In the rabbit, the part of the basal ganglia that is involved in oro-facial movements may also be larger.
Acknowledgements This study was supported by grants-in-aid (Nos. 09771534, 10557164 and 10307045) from the Japanese Ministry of Education, Science and Culture.
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93 – 110. Liu, Z.J., Masuda, Y., Inoue, T., Fuchihata, H., Sumida, A., Takada, K., Morimoto, T., 1993. Coordination of cortically induced rhythmical jaw and tongue movements in rabbit. J. Neurophysiol. 69, 569 – 584. Lund, J.P., 1991. Mastication and its control by the brain stem. Crit. Rev. Oral. Biol. Med. 2, 33 – 64. Lund, J.P., Lamarre, Y., 1974. Activity of neurons in the lower precentral cortex during voluntary and rhythmical jaw movements in the monkey. Exp. Brain Res. 19, 282 – 299. Lund, J.P., Sasamoto, K., Murakami, T., Olsson, K.A., 1984. Analysis of rhythmical jaw movements produced by electrical stimulation of motor-sensory cortex of the rabbits. J. Neurophysiol. 52, 1014 – 1029. Masuda, Y., Morimoto, T., Hidaka, O., Kato, T., Matsuo, R., Inoue, T., Kobayashi, M., Taylor, A., 1997. Modulation of jaw muscle spindle discharge during mastication in the rabbit. J. Neurophysiol. 77, 2227 – 2231. Masuda, Y., Nakamura, O., Kato, T., Mizuno, J., Kobayashi, M., Inoue, T., Matsuo, R., Morimoto, T., 1995. Discharge pattern of neurons in the cortical masticatory area during mastication in the awake rabbit. Forth IBRO Congress of Neuroscience, Abstracts, p347. Matsumoto, N., Hanakawa, T., Maki, S., Graybiel, A.M., Kimura, M., 1999. Nigrostriatal dopamine system in learning to perform sequential motor tasks in a predictive manner. J. Neurophysiol. 82, 978 – 998. McFarland, C., Lund, J.P., 1993. An investigation of the coupling between respiration, mastication, and swallowing in the awake rabbit. J. Neurophysiol. 69, 95 – 108. Mink, J.W., Thach, W.T., 1991. Basal ganglia motor control. I. Nonexclusive relation of pallidal discharge to five movement modes. J. Neurophysiol. 65, 273 – 300. Mora, F., Mogenson, G.J., Rolls, E.T., 1977. Activity of neurons in the region of the substantia nigra during feeding in the monkey. Brain Res. 133, 267 – 276. Morimoto, T., Inoue, T., Masuda, Y., Nagashima, T., 1989. Sensory components facilitating jaw-closing muscle activities in the rabbit. Exp. Brain Res. 76, 424 – 440. Morimoto, T., Inoue, T., Nakamura, T., Kawamura, Y., 1985. Characteristics of rhythmic jaw movements of the rabbit. Arch. Oral Biol. 30, 673 – 677. Nakamura, Y., Katakura, N., 1995. Generation of masticatory rhythm in the brainstem. Neurosci. Res. 23, 1 – 19. Nishino, H., Hattori, S., Muramoto, K., Ono, T., 1991. Basal ganglia neural activity during operant feeding behavior in the monkey: Relation to sensory integration and motor execution. Brain Res. Bull. 27, 463 – 468. Nozaki, S., Iriki, A., Nakamura, Y., 1986a. Localization of central rhythm generator involved in cortically induced rhythmical masticatory jaw-opening movement in the guinea pig. J. Neurophysiol. 55, 806 – 825. Nozaki, S., Iriki, A., Nakamura, Y., 1986b. Role of corticobulbar projection neurons in cortically induced rhythmical masticatory jaw-opening movement in the guinea pig. J. Neurophysiol. 55, 826 – 845. Palfai, T., Armstrong, D., Courtney, C.L., 1984. Effect of l-dopa or bromocriptine on feeding and motor behavior of rats with lesions in globus pallidus. Physiol. Behav. 33, 283 – 289. Pisa, M., 1988. Motor somatotopy in the striatum of rat: manipulation, biting and gait. Behav. Brain Res. 27, 21 – 35. Pisa, M., Schranz, J.A., 1988. Dissociable motor roles of the rat’s striatum conform to a somatotopic model. Behav. Neurosci. 102, 429 – 440. Schneider, J.S., Morse, J.R., Lidsky, T.I., 1982. Somatosensory properties of globus pallidus neurons in awake cats. Exp. Brain Res. 46, 311 – 314.
Y. Masuda et al. / Neuroscience Research 39 (2001) 11–19 Schwartz, S., Enomoto, S., Valiquette, C., Lund, J.P., 1989. Mastication in the rabbit: A description of movement and muscle activity. J. Neurophysiol. 62, 273–287. Szczypka, M.S., Rainey, M.A., Kim, D.S., Alaynick, W.A., Matsumoto, A.M., Palmiter, R.D., 1999. Feeding behavior in do-
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pamine-deficient mice. Proc. Natl. Acad. Sci. USA 96, 12138 – 12143. Zigmond, M., Stricker, E.M., 1972. Deficits in feeding behavior after intraventicular injection of 6-hydroxydopamine in rats. Science 177, 1211 – 1214.
Neuronal activity in the putamen and the globus pallidus of rabbit during mastication Yuji Masuda *, Takafumi Kato, Osamu Hidaka 1, Ryuji Matsuo 2, Tomio Inoue 3, Koichi Iwata, Toshifumi Morimoto Department of Oral Physiology, Faculty of Dentistry, Osaka Uni6ersity, 1 -8 Yamadaoka, Suita, Osaka 565 -0871, Japan Received 6 July 2000; accepted 8 August 2000
Abstract The pattern of jaw movements is changed during a masticatory sequence from ingestion of food to its deglutition. The masticatory sequence is divided into three distinct stages in the rabbit. However, the neural mechanism involved in the alteration of the masticatory stages is still unknown. This study was designed to determine whether neuronal activity in the putamen and globus pallidus is related to the alteration of the masticatory stages. Fifty-three percent of the recorded neurons showed significant alterations of activity during mastication. Of these neurons, 16% changed their firing frequency throughout the masticatory sequence (sequence-related neurons) and 84% changed their firing frequency with the transition of the masticatory stages (stage-related neurons). The stage-related neurons were classified into two groups based on their neuronal activity patterns observed during mastication, i.e. simple type and complex type. The former are the neurons that were either facilitated or inhibited once during mastication, and the latter are those showing the facilitation or inhibition twice or more during mastication. Complex-type neurons were observed more frequently in the globus pallidus than in the putamen. These results suggest that the basal ganglia is involved in mastication and may related to the transition between the masticatory stages. © 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. Keywords: Mastication; Jaw movement; Putamen; Globus pallidus; Neuronal activity; Sequence; Rabbit
1. Introduction The masticatory sequence is a whole set of movements from ingestion to swallowing. It is made up of masticatory cycles that change in movement pattern as the food is gathered, moved backward to the molar teeth, then broken down and prepared for swallowing (Lund, 1991). The masticatory sequence can be divided into three distinct stages (stage I, IIa, IIb) in the rabbit based on the form of the jaw movements (Morimoto et al., 1985; Schwartz et al., 1989). The food is transported * Corresponding author. Tel.: +81-6-6879-2882; fax: + 81-6-68792885. E-mail address: [email protected] (Y. Masuda). 1 Department of Orthodontics and Dentofacial Orthopedics, Osaka University Faculty of Dentistry, Suita, Osaka 565-0871, Japan. 2 Department of Oral Physiology, Okayama University Dental School, Okayama, Okayama 700-8525, Japan. 3 Department of Oral Physiology, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555 Japan.
back to the molar teeth during stage I and ground up during stage II. The transition from stage I to II occurs abruptly. It is now generally accepted that the motor command for the basic pattern of rhythmical oral-facial movements during chewing is generated by a neuronal population in the brain stem (central pattern generator) (Nakamura and Katakura, 1995 for review). Sensory input from a variety of intraoral, joint, and muscle receptors interact with the central control system in the brain stem to adapt the program of chewing movements to the characteristics of the food (Morimoto et al., 1989; Hidaka et al., 1997). Therefore, the jaw movements for chewing have been called semi-automatic movements. However, it is still unclear what neural mechanism is involved in the transition from stage I, in which the animal manipulates the food and leads to the semi-automatic chewing movements, to stage II. Many investigations have demonstrated that feeding deficits are caused by lesions of the striatum or globus
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pallidus (GP), or destruction of nigrostriatal dopaminergic neurons (Zigmond and Stricker, 1972; Labuszewski et al., 1981; Palfai et al., 1984; Pisa, 1988; Pisa and Schranz, 1988; Jicha and Salamone, 1991; Szczypka et al., 1999). These kinds of feeding deficits have been attributed to sensory – motor impairment and/or a loss of the motivation to eat. Some investigations have discussed impairment of oro-facial movements as a potential mechanism of these feeding deficits. Pisa and Schranz (1988) have found that lesions of the ventrolateral striatum impaired the reaching movements of the tongue. Moreover, Pisa (1988) reported that lesions of the lateral striatum impaired motor performance during feeding, and lesions of the ventral region especially influenced mouth – tongue movements. On the other hand, Labuszewski et al. (1981) observed that during the early phase of recovery of feeding behavior after GP lesion, rats spilled large quantities of food while chewing. These findings showed that the basal ganglia might play a role in the control of masticatory movements, including jaw and tongue and other orofacial movements. Many studies have provided evidence for the hypothesis that the basal ganglia is involved in the sequence of actions of learned hand movement (Kimura, 1990; Kimura et al., 1992; Kermadi and Joseph, 1995; Matsumoto et al., 1999), trained head movement (Gardiner and Kitai, 1992), and grooming (Berridge and Whishaw, 1992; Cromwell and Berridge, 1996). Assuming that mastication, consisting of food transport, chewing and swallowing, was a sequenced action, we reasoned that the basal ganglia might be involved in the progress of mastication. In this study, therefore, in order to investigate the relationship between the masticatory movements and neuronal activity of the basal ganglia in the awake rabbit, we examined whether neurons in the putamen (PUT) and GP alter their firing rates in relation to the masticatory movements and also whether the alteration of the firing frequency in the PUT and GP neurons related to the progress of mastication.
2. Materials and methods Twelve male rabbits (2.3 – 3.0 kg), in whom the jaw movement patterns during the masticatory sequence had been well analyzed (Morimoto et al., 1985; Schwartz et al., 1989), were used. All the surgical procedures were reviewed and approved by the Osaka University Faculty of Dentistry Intramural Animal Care and Use Committee. The animals were anesthetized with pentobarbital sodium (20 mg/kg) and ketamine HCl (20 mg/kg) via an ear vein. Supplementary doses of anesthetic were given when necessary. During surgery, anesthesia was maintained at such a
level that no reflexive jaw opening resulted from pinching the facial skin. The procedures for attachment of a phototransistor array to the mandible for tracing jaw movements and the insertion of pairs of enamel-coated copper wires (150 mm diameter, 5 mm spacing, 1.5 mm tip bared) into the left masseter and digastric muscles for electromyogram (EMG) recording were the same as those reported elsewhere (Inoue et al., 1989). A stainless steel cylinder for a modified Evarts type of micromanipulator (MO-95, Narishige-Kagaku, Tokyo, Japan) was fixed at the right parietal area for recording the neuronal activity in the basal ganglia. The rabbits were maintained in good health by veterinary care throughout the experimental period. Recordings were started at least 4 days after the surgery and lasted several days (each daily session lasted about 2 h). During the experiments, the rabbit’s head was supported in a frame by means of skull screws. Rabbits readily accepted this type of fixation and chewed food without apparent disturbance. Neuronal activity was recorded simultaneously with EMG and jaw movements as described elsewhere (Masuda et al., 1997). A glass-coated metal microelectrode with an impedance of 1–3 MV at 1 kHz was inserted vertically through the right cerebral cortex towards the basal ganglia. The electrode penetrations were located between 0 and 1 mm anterior to bregma and between 5.0 and 7.0 mm lateral to the midline. Four pieces of carrot, cut as quadrangular prisms (3.5× 3.5× 10 mm), were inserted at one time into the rabbit’s mouth. Once we had succeeded in recording the neuronal activity during mastication in a given rabbit, the recording sites were marked by passing a negative current of 30 mA through the recording electrode for 10 s under deep anesthesia at the end of experiment. The rabbit was perfused with saline followed by formalin (10%). In short, recordings and markings were performed by means of a single electrode in each rabbit. The recording sites were later identified on 50 mm sections of the brain stained with cresyl violet. The data were stored on a digital tape recorder (PC-208, Sony-Magnescale, Tokyo, Japan) and spike discrimination and data processing were later performed using a Cambridge Electronics 1401 data acquisition board and Spike2 analysis package (Cambridge Electronic Design, Cambridge, UK). For each neuron, the activity was analyzed from 6 s before the onset of jaw opening in the first cycle during mastication to the end of the masticatory sequence. To determine the change in activity during mastication, peri-event histograms of the entire masticatory sequence for at least three trials were made using 100 ms bins triggered by the onset of the first jaw opening. From each histogram, the mean number of spikes and standard deviation (S.D.) of spontaneous unit discharge were calculated for a 1.5 s period during the resting condition (commonly 4 s preceding the onset of mastication).
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A change in activity was determined to have occurred if, considering 100 ms bin histograms, the number of spikes increased or decreased by at least 2 S.D. of the mean of the spontaneous unit discharge, and lasted for at least 300 ms (3 bins). The neuronal activity, if a change in activity during mastication was detected, was examined to determine whether its change related to the transition between the masticatory stages, using the peri-event histograms triggered by the point of transition from stage I to II (at least three trials). We defined neurons, which showed the same alterations before and after the point of transition from stage I to II, as sequence-related neuron, and neurons, which showed different neuronal activity between stage I and II, as stage-related neuron. Stage IIa and IIb have been regarded as the molar chewing stage and the swallowing preparatory stage, respectively. However, a later study demonstrated that swallowing occurred during the chewing stage (McFarland and Lund, 1993). In this study, we did not examine the transition from stage IIa to IIb because of the slight difference of jaw movement pattern observed during the stages and the unclear distinction of the functional role of these two stages.
3. Results The activity of a total of 93 single neurons recorded in the PUT (n=34) and GP (n =59) of the 12 awake rabbits was successfully studied throughout the whole masticatory sequence. Spontaneous activity was observed in all of the 93 recorded neurons. The mean frequency of spontaneous activity of the neurons in the PUT (26.39 18.0 Hz; mean9 S.D.) was significantly (U-test, P B0.01) lower than that in the GP (41.49 17.0 Hz) (Fig. 1).
Fig. 1. A histogram of the mean frequency of spontaneous activity in the recorded neurons from the PUT (solid column) and the GP (open column). Note: the mean frequency of spontaneous activity of the neurons in PUT was significantly (U-test, PB 0.01) lower than that in the GP.
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Of the 34 PUT neurons, 20 showed alterations of activity above and/or below 2 S.D. of the mean frequency of spontaneous activity during mastication, and of the 59 GP neurons, 29 had similar alterations in activity. The frequency of occurrence of these neurons in the PUT was not significantly different from that found in GP (Fisher’s exact test, P \ 0.05). Of the 20 PUT neurons and the 29 GP neurons which changed firing frequency during mastication, 17 PUT neurons and 24 GP neurons showed this alteration at the transition from stage I to II (stage-related neurons). The remaining 3 PUT neurons and 5 GP neurons changed firing frequency throughout the mastication sequence (sequence-related neurons). The ratio of the stage-related neurons in the PUT was not significantly different from that in the GP (Fisher’s exact test, P\ 0.05).
3.1. Sequence-related neurons Fig. 2 illustrates an example of neuronal activity obtained from the GP (Fig. 2D), showing the increments of firing rates throughout the masticatory sequence. The masticatory sequence was confirmed to be divided into three stages (I, IIa and IIb) as reported previously (Morimoto et al., 1985), and the movement traces on the frontal plane during each stage are shown in Fig. 2A. When the food materials were inserted, the touch of the syringe to the lip induced the first jaw opening and commenced stage I. The rabbit accepted the food and transferred it to the molar region at stage I during which jaw movements consisted of irregular repetitive simple open-close movements with small lateral movements. During stage II, the rabbit crushed and ground foods with regular jaw movements. The firing rate of this neuron increased at the onset of the mastication, and this increment lasted to the end of masticatory sequence. In stage II, firing frequency did not relate to the jaw opening or jaw closing. Rather, the alteration of firing frequency depended on the change in masticatory sequence, not on the masticatory cycle (Fig. 2B and C). All neurons related to mastication, which were recorded from the PUT and the GP in this study, altered their firing frequency according to the change in masticatory stages or sequence. Fig. 3 shows the neuronal activity of a sequence-related neuron recorded from the PUT (Fig. 3B) during ten successive trials of mastication. This neuron increased its firing frequency throughout the masticatory sequence on every one of the ten trials. The change in firing frequency of all the recorded neurons was consist on every trial of mastication like neuronal activity shown in Fig. 3. In this study, to determine the change in activity during mastication, peri-event histograms of the entire masticatory sequence for at least three trials were used. All of the three sequence-related neurons recorded from the PUT showed an increase of activity through-
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firing rate disappeared at the point of transition from stage I to II (Fig. 4B). Stage-related neurons were classified into two groups based on their neuronal activity patterns observed during mastication. We defined an event as a period in which the firing rate was continually out of the range of the mean spontaneous firing rate (mean92 S.D.). Neurons showing one event throughout the masticatory sequence were named simple-type neurons (Fig. 5), and those showing two or more events were termed complex-type neurons (Fig. 6). Most of the stage-related PUT neurons (15/17) were simple-type neurons, whereas 58% of the stage-related GP neurons (14/24) were simple-type neurons. The remaining 42% of the GP neurons (10/24) were regarded as the complex type.
Fig. 2. The activity of a sequence-related neuron from the GP. (A) The modulation of neuronal activity in the GP throughout a masticatory sequence. The upper most and the second records show the firing rate and the spike record, respectively. Ver and Hor: vertical and horizontal jaw movements. Mass and Dig: EMGs of the masseter and digastric muscles. At the bottom: jaw movements on the frontal plane in stage I, IIa and IIb. Small arrows indicate the direction of jaw movements. (B) Expanded records of the hatched parts in A. (C) Phase relationship of unit discharges to jaw movement cycles. Averaged jaw movements of ten masticatory cycles (top two records) and histogram of neuronal activity triggered by the jaw-closed position. (D) Recorded site of this neuron is shown by *. PUT, putamen. GP, globus pallidus. IC, internal capsule. AC, anterior commissure.
out mastication. Of the five sequence-related neurons from the GP, four neurons has an increment in firing rate and one neuron had a decrement of firing rate throughout mastication.
3.2. Stage-related neurons Fig. 4 shows the activity of a stage-related neuron located in the PUT during three masticatory trials aligned by the onset of the first jaw opening (A) and by the point of transition from stage I to II (B). This neuron showed an increase in firing rate preceding the onset of mastication (Fig. 4A). This increment of the
Fig. 3. The activity of a sequence-related neuron from the PUT. (A) The activity of a PUT neuron during ten trials of mastication. Traces have been aligned by the onset of the first jaw opening. The horizontal dotted line on the histogram indicates the mean + 2 S.D. of spontaneous firing frequency. (B) Recorded site of this neuron is shown by *. PUT, putamen. GP, globus pallidus. IC, internal capsule. AC, anterior commissure. (C) 40 superimposed traces of the neuron’s wave form.
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Fig. 4. The activity of a stage-related neuron from the PUT during three trials of mastication. The traces have been aligned by the onset of the first jaw opening (A) and the point of the transition from stage I to II (B). The horizontal dotted line on the histograms indicate the mean +2 S.D. of spontaneous firing frequency.
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Fig. 5. The activity of simple-type neurons from the PUT (A) and the GP (B) during three trials of mastication. The traces have been aligned by the onset of the first jaw opening. The upper and lower horizontal dotted line on the histograms indicate the mean +2 S.D. and mean−2 S.D. of spontaneous firing frequency, respectively.
3.2.1. Simple-type neurons Fourteen of 15 PUT simple-type neurons showed an alteration of firing only during stage I; 11 showed an increase (Fig. 5A) whereas three showed a decrease. They did not change their firing frequency in stage II. One of 15 simple-type neurons increased only during stage II. Thirteen of the 14 GP simple-type neurons changed their firing rate only during stage I. All of their alterations (11: increase, 2: decrease) during stage I did not last to stage II (Fig. 5B). Only one simple-type GP neuron, which did not change its firing frequency during stage I, did decrease during stage II. 3.2.2. Complex-type neurons Of the PUT stage-related neurons, two neurons were regarded as complex-type neurons. One showed an increase during stage I and a decrease during stage II. Another neuron showed a decrease during stage I and an increase during stage II. Five of the ten GP complex-type neurons, showed both an increase and decrease during a masticatory sequence. Two of them showed an increase during stage I and a decrease during stage II, whereas three of them showed a decrease during stage I and an increase during stage II (Fig. 6A). Four of the ten GP complextype neurons showed a decrease during stage I and a
Fig. 6. The activity of two kinds of complex-type neurons from the GP during four trials of mastication. The traces have been aligned by the point of the transition from stage I to II. The upper and lower horizontal dotted line on the histograms indicate the mean + 2 S.D. and mean−2 S.D. of spontaneous firing frequency, respectively.
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4.1. Spontaneous acti6ity
Fig. 7. The location of neurons on representative histological sections at the level of 1 mm (left) and 0 mm (right) anterior to bregma that changed their firing frequency throughout mastication, the location of the simple-type and complex-type neurons, and the location of neurons who’s activity was not related to mastication. Triangle, open circles, filled circles and crosses indicate neurons changed firing frequency throughout mastication, simple-type neurons, complex-type neurons and neurons not related to mastication, respectively. PUT, putamen. CD, caudate nucleus. GP, globus pallidus. IC, internal capsule. EC, external capsule. AC, anterior commissure.
decrease during stage II after the firing rate came back to the range of the mean spontaneous firing rate (mean9 2 S.D.) at the transition between stages (Fig. 6B). The remaining neuron, whose firing rate decreased immediately before the onset of the first jaw opening, showed an increase during stage I without alteration during stage II.
3.3. Location of recorded neurons Fig. 7 shows the recording site of neurons that changed firing frequency throughout mastication, both simple-type and complex-type neurons, and also neurons not related to mastication which are plotted collectively in drawings of the representative histological sections at the level of 0 and 1 mm anterior to bregma. Neurons related and unrelated to mastication were found throughout the PUT and GP. Furthermore, there were no preferential locations of simple-type or complex-type neurons in the PUT and GP.
4. Discussion The present study has shown that about 50% of the PUT and the GP neurons altered their firing frequency in relation to mastication in correspondence with changes in masticatory stages or masticatory sequence but not within masticatory cycles. These findings suggest that the basal ganglia may be involved in the adaptation of the masticatory process based on the circumstances in the mouth.
For every neuron we defined the mean frequency for the 1.5 s period preceding the onset of mastication as the mean frequency of spontaneous activity. The mean frequency of spontaneous activity of the neurons in the PUT was significantly lower than that in the GP (Fig. 1). Although the difference between the PUT and the GP was consistent with the findings of many earlier investigations, the levels of activity found in the present study differed considerably from those observed in other species (DeLong, 1972; Schneider et al., 1982; DeLong et al., 1985; Kimura, 1990; Gardiner and Kitai, 1992; Cheuruel et al., 1994). Based on many investigations, firing frequency of neurons in the striatum is known to be very low (less than 10 Hz), while that in the GP is very high (50–100 Hz). In the monkey, it was observed that in the external segment of GP (Gpe), which is equivalent to the GP in the rabbit, neurons were divided into two groups on the basis of their baseline firing frequency (1) ones with low spontaneous activity of around 8 spikes per s, (2) ones with high activity of around 80 spikes per s (Mink and Thach, 1991). However, in another study, very low levels of activity were also described (Iansek and Porter, 1980). In our study, GP neurons in rabbits could not be divided into two groups according to the histogram of the spontaneous activity. Rather, the spontaneous activity of GP neurons showed a wide range of levels. The study of Jaeger et al. (1993) reported the mean baseline firing rate of GPe neurons was around 40 spikes per s, which is similar to our data. Although the PUT neurons in this study could be divided into two groups according to mean spontaneous firing frequency, as well as the PUT neurons in the primate, the firing frequency during the resting condition of the PUT neurons in our study was higher than that in previous studies. These differences in the firing rate could be related to a sample bias, and/or species differences. Furthermore, it may be due to differences in the experimental conditions. Our experiment did not require the performance of a task. Rather, the experimenter just gave food to the animals. Under our experimental conditions, the fact that the animals were always ready to perform the ingestion behavior may have modulated the firing frequency of neurons throughout the experiments.
4.2. Acti6ity patterns related to mastication There are a few studies that examined the neural activity of the basal ganglia in relation to the masticatory sequence. Nishino et al. (1991), who recorded neural activity from the caudate nucleus, GP, and the substantia nigra pars reticulata during operant feeding behavior in the monkey, found that some neurons
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altered their firing frequency during the ingestion of solid-food reward. The majority of these responses consisted of long-lasting inhibition throughout ingestion, as with the sequence-related neurons in this study. The increase of the firing rates of PUT neurons after the delivery of a reward (apple juice) were examined by Apicella et al. (1991). Those responses showed a short or long single peak of increased activity that was temporally unrelated to EMG activity in the masseter muscle. Although jaw movement patterns were not examined in that study, our results are consistent with their observation that neuronal responses did not relate to each masticatory cycle. It has been demonstrated that the rhythm of the masticatory cycles is formed in the brain stem (Nozaki et al., 1986a,b). Although the jaw movements were rhythmic throughout the masticatory sequence, the pattern of jaw movements, the sensitivity of the afferent from the trigeminal area and the aim of the jaw movements are different between the stages (Morimoto et al., 1985; Schwartz et al., 1989; Masuda et al., 1997). Therefore, the jaw movements in each stage appeared to be distinct movements from each other. However, it is unclear which neuronal mechanism controls the alteration of jaw movements associated with masticatory progress. The present results show that the discharge pattern in some of the neurons recorded from the basal ganglia related to the transition between these stages, indicating that the basal ganglia might play an important role in the transition between stages. Many investigations have suggested that the basal ganglia has a specific role in the construction and execution of motor plans (Hikosaka et al., 1989a,b,c; Kermadi and Joseph, 1995; see review Graybiel, 1995). The PUT is thought to be involved in the initiation of movement by selecting a particular learned movement associated with contextual sensory cues (Kimura, 1990). The basal ganglia may have a similar relationship to mastication. The stage-related neurons exhibited a variety of activity patterns. The neurons were classified into two types (simple and complex type) on the basis of their activity patterns throughout the masticatory sequence. Both types of neurons were related to the transition between stages. Most of the PUT neurons related to mastication were simple-type neurons, whereas 42% of the GP neurons were complex-type neurons. Anatomical data indicate that the GP receives input from the striatum and the input has convergence (Flaherty and Graybiel, 1993). If it is plausible that complex-type neurons are linked to the transition of the stages more strongly than simple-type neurons, the finding that complex-type neurons were observed more frequently in the GP than in the PUT suggests that the neural network in the basal ganglia may provide the information to emphasize the transition of the stages. It is reported that some neurons in the cortical
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masticatory area activated throughout mastication are not related to the masticatory cycles (Lund and Lamarre, 1974), and change firing frequency depending on the alteration of the stages (Masuda et al., 1995). On the other hand, there are neurons in the substantia nigra that are tonically activated during drinking behavior (Mora et al., 1977). The PUT has projections from both the cerebral cortex and substantia nigra. The discharge pattern of the PUT neurons recorded in this study may be influenced by the neural activity of these two areas.
4.3. Location of the neurons related to mastication In this study, we obtained data from the PUT and GP rostro-caudally at the level of the anterior commissure (the electrode penetrations were located between 0 and 1 mm anterior to bregma and between 5.0 and 7.0 mm lateral to the midline). In the rabbit, there has been no study of the relationship between the basal ganglia and oral motor behavior. In primates, somatotopic organization was clearly evident with respect to both the sensorimotor response properties of PUT neurons and the anatomic foci of microstimulation-evoked movements (Alexander and DeLong, 1985). Representation of orofacial structures was confined to the ventral portion of the PUT. In the rabbit, the neurons recorded in this study, which changed their activity during mastication, were located throughout the PUT and the GP in certain rostorocaudal levels. The somatotopic organization found in the somatosensory cortex in the rabbit indicates that the orofacial sensory projection area occupied most of somatosensory cortex (Gould, 1986). Further, the cortical masticatory area, in which electrical stimulation induced rhythmical jaw movements, also occupied large area of frontal cortex in the rabbits (Lund et al., 1984; Liu et al., 1993). This means that in rabbits the orofacial region was functionally more important for manipulation than the other body parts (e.g. forepaw, forelimb etc.). In the rabbit, the part of the basal ganglia that is involved in oro-facial movements may also be larger.
Acknowledgements This study was supported by grants-in-aid (Nos. 09771534, 10557164 and 10307045) from the Japanese Ministry of Education, Science and Culture.
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