- Email: [email protected]
Changes in jaw reflexes by stimulation of the hypothalamus in anesthetized rabbits
Neuroscience Research 41 (2001) 61 – 65
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Changes in jaw reflexes by stimulation of the hypothalamus in anesthetized rabbits Makoto Inoue a,*, Kayoko Nozawa-Inoue b, Yozo Miyaoka c, Yoshiaki Yamada a a
Di6ision of Oral Physiology, Department of Oral Biological Science, Niigata Uni6ersity Graduate School of Medical and Dental Sciences, Niigata 951 -8514, Japan b Di6ision of Oral Anatomy, Department of Oral Biological Science, Niigata Uni6ersity Graduate School of Medical and Dental Sciences, Niigata 951 -8514, Japan c Department of Health and Nutrition, Niigata Uni6ersity of Health and Welfare, Niigata 950 -3198, Japan Received 9 April 2001; accepted 15 June 2001
Abstract Changes in the masseteric monosynaptic reflex (MMR) and jaw-opening reflex (JOR) responses resulting from conditioning stimulation in the hypothalamus were studied in anesthetized rabbits. Stimulation of the lateral hypothalamus evoked a facilitation of the MMR and an inhibitory or facilitatory effect on the JOR. The facilitatory effect on JOR was stronger than that on the MMR. The facilitatory effective site for the JOR was in the dorsal and lateral directions as compared to the inhibitory field. The results suggest two functionally distinct regions in the lateral hypothalamus that separately project to the jaw-opening muscles. © 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. Keywords: Jaw reflex; Lateral hypothalamus; Electrical stimulation; Rabbit
The authors demonstrated that jaw-closing reflex amplitudes were markedly reduced in active sleep (AS) but it was intermittently and drastically increased during the rapid eye movement (REM) period of AS, and the jaw-opening reflex (JOR) remained inhibited throughout AS (Inoue et al., 1999). These results indicated predominantly a difference in the excitability between the two groups, jaw-closing and jaw-opening muscles, during the REM period. In this paper, we have examined the specific regions in the brain, which may be responsible for the modulation of such jaw reflexes. Electrical stimulation of the hypothalamus induces attack or defense responses in which opening and closing jaws are obvious elements (Brody et al., 1969; Brown et al., 1969; Chi and Flynn, 1971), and modulates jaw reflexes (Achari and Thexton, 1972; Landgren and Olsson, 1980). There are also some evidence that * Corresponding author. Division of Oral Physiology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan. Tel.: +81-25227-2824; fax: +81-25-225-0281. E-mail address: [email protected] (M. Inoue).
the hypothalamic neurons send their axons extensively to descending structures including some nuclei in the vicinity of the trigeminal motor nucleus such as the trigeminal mesencephalic nucleus and nucleus reticularis parvocellularis (Hosoya and Matsushita, 1981; Nagy et al., 1986). Additionally, previous physiological and anatomical studies suggest that the lateral hypothalamus is implicated in control of electroencephalographic desynchrony and arousal action (Jurkowlaniec et al., 1996; Lin et al., 1989; Semba, 1993; Szymusiak et al., 1989). However, the relationship between the hypothalamic jaw movement-related regions and their activities during sleep still remains to be substantiated. Although the final goal of our study is to clarify a physiological interaction between the hypothalamic and trigeminal motor activity, the aim of the present work, as a first step, was to localize the region in the hypothalamus that has modulatory effects on the jaw reflexes, and to evaluate the modulatory response. Twelve male rabbits, weighing between 2.0 and 2.5 kg, were used. They were anesthetized initially with urethane (1.2 g/kg, iv), and anesthesia was maintained with a supplemental dose of urethane (0.1 g/kg/h, iv).
0168-0102/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. PII: S 0 1 6 8 - 0 1 0 2 ( 0 1 ) 0 0 2 6 0 - 7
62
M. Inoue et al. / Neuroscience Research 41 (2001) 61–65
Surgical preparations of the animals were similar to those we reported previously (Inoue, et al., 1999). Briefly, electrodes for electromyographic (EMG) recordings were implanted into the right masseter and digastric muscles. For test stimulations, the trigeminal mesencephalic nucleus was stimulated (three train pulses of 0.1 ms and 2 kHz) to evoke the masseteric monosynaptic reflex response (MMR), and the inferior alveolar nerve was stimulated (three train pulses of 0.1 ms and 2 kHz) to evoke the JOR. The strength of stimulation was set at 1.5 times the threshold for each reflex. For conditioning stimulation, a bipolar needle electrode was inserted into the right hypothalamus by means of Sawyer coordinates (Sawyer and Everette, 1954). These electrodes were moved in steps of 0.5 mm and the hypothalamus was stimulated (five train pulses of 0.2 ms and 2 kHz, 0.2 mA). The interval between the conditioning and test
stimuli (the C–T interval) was varied from 0 to 100 ms in 5 ms steps. Evoked EMGs were recorded and analyzed by means of a computer (Power Mac 5300cs: Apple) and interactive software (MacLab: ADI). We evaluated peak-to-peak amplitudes of the MMR and JOR recorded during each session using the mean amplitude of 20 times recordings, and then normalized individual mean amplitudes to the control MMR and JOR. We evaluated one position as most facilitatory or inhibitory for the jaw reflex activity in one animal if it was effective statistically. Data were analyzed using the analysis of variance and the Tukey’s multiple comparisons test. At the end of experiment, the animals were killed with an overdose of the anesthetic. The brain was removed and tissue sections were subjected to histological preparations to evaluate the location of the electrode tip in the hypothalamus.
Fig. 1. Effects of electrical stimulation in the lateral hypothalamus on the masseteric monosynaptic reflex (MMR) and jaw opening reflex (JOR). In diagram A, changes of normalized values in the MMR are indicated. In diagrams B – C, changes of normalized values in the JOR are indicated. Diagrams D – F indicate sample records averaged in A –C, respectively. Arrows indicate the time of test stimulation. Sample (a) is a control record. Samples (b – f) correspond to points shown in A – C. Diagrams G – H indicate the position of the electrode tip in the hypothalamus ( , , and
) and the effect of each stimulation is shown by the same symbol in A – B, respectively. Diagram I indicates the position of the electrode tip in the hypothalamus ( and ) and the effect of each stimulation is shown by the same symbol in C. Amy, amygdala; IC, internal capsule; FX, fornix; GP, globus pallidus; LHA, lateral hypothalamic area; OT, optic tract; Put, putamen; SO, supraoptic nucleus; IIIV, third ventricle. *PB0.01.
M. Inoue et al. / Neuroscience Research 41 (2001) 61–65 Table 1 Parameters of masseteric monosynaptic reflex (MMR) and jaw-opening reflex (JOR) n
MMR JOR
9 9
Facilitation
Inhibition
n%
Amplitude
n%
Amplitude
3 5
2.19 0.9 10.2 9 4.7
0 5
0.3 9 0.1
n is number of samples tested. n% is number of samples from which modulation was observed. Amplitude represents the normalized value. Each value is mean of means 9 SEM.
Fig. 1(A,D) shows an example of the effect on the MMR of locating the electrode tip in the lateral hypothalamus as shown in Fig. 1(G). A typical effect on the MMR was a small and short facilitation (Fig. 1(A) and Table 1). The C–T interval of this facilitation was B 10 ms. This small facilitatory effect on the MMR was observed only in three out of nine animals, and no effect in the rest. The modulation of JOR was evaluated along with the MMR. Fig. 1(B,E and C,H) shows examples of the effect of stimulating the lateral hypothalamus on the JOR as shown in Fig. 1(H and I), respectively. The typical effect on the JOR was either large facilitation or strong inhibition (Fig. 1(B– C) and Table 1). The facilitatory effect on the JOR (10.29 4.7 times of control) was much larger than the MMR (2.19 0.9 times of control) (Table 1). The C– T interval of the facilitation was 20 ms and that of the inhibition was 30 ms. All these effective sites were consid-
63
erably small and there was no effect on these reflex responses when the stimulating electrodes were moved to other regions. Fig. 2 illustrates histological location of the electrode tip in part of the hypothalamus from which the maximal effects on the MMR and JOR could be evoked in all animals. The effective sites on the MMR were limited to the rostral portion of the lateral hypothalamus and the area just lateral to the fornix. The effective sites on the JOR also appeared to be in the lateral hypothalamus but the area was larger in the lateral and caudal directions than those for the MMR. The electrode tip sites that had facilitatory effects on the JOR seemed to be clustered more dorsally and laterally than those where the inhibitory effects were evoked (Fig. 2). There were no stimulation sites that simultaneously affected amplitudes of MMR and JOR. Present data showed that a facilitatory effect on the MMR was small as compared to data shown by Landgren and Olsson (1980) (\10 times of control) and it was observed only in three out of nine animals. In addition, we observed not only an inhibitory but also a facilitatory effect on the JOR. Facilitation of the JOR was much stronger than that of the MMR in our data (compare Fig. 1(A–B)). To interpret these results, we must consider the possibility of whether it was cell bodies in the lateral hypothalamus which were excited or axons from other structures passing through the hypothalamus. Several pathways which were activated can affect the JOR through the region near the lateral hypothalamus. King et al. (1955) reported facilitation of the JOR following
Fig. 2. These diagrams show the location in the lateral hypothalamus of the electrode tip. Facilitation of the masseteric monosynaptic reflex (MMR) ( ), facilitation of the jaw opening reflex (JOR) ( ) and inhibition of the JOR () were observed after the hypothalamus was stimulated. These sites had the maximal effects on the MMR and JOR. Amy, amygdala; C, caudate nucleus; IC, internal capsule; FX, fornix; GP, globus pallidus; LHA, lateral hypothalamic area; OT, optic tract; Put, putamen; SO, supraoptic nucleus; IIIV, third ventricle.
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M. Inoue et al. / Neuroscience Research 41 (2001) 61–65
the stimulation of the pathway from the motor cortex and caudate to the reticular formation. Furthermore, electrical stimulation of the amygdala has known to modulate jaw muscle activity (Bobo and Bonvallet, 1975; Ohta, 1984). It is possible that we might have stimulated a part of them. However, the intensity of stimulus used by King et al. (2– 4 mA) was much higher than that used in this study (0.2 mA) and we never found any other modulation of jaw reflexes when electrodes were moved to other sites. Therefore, it is unlikely that we evoked axon activity in such descending pathways. The stimulus condition used by Landgren and Olsson (1980) (10 pulses, 0.5 ms and 0.5 mA) to facilitate the MMR was also higher than present data. This stimulation might lead to a large facilitation of MMR as compared to our results. The present results did not indicate a large facilitation of masseter muscle activity following the stimulation of the lateral hypothalamus, suggesting that this area is not responsible for the drastic change of excitability in masseter muscle during sleep. Landgren and Olsson (1980) demonstrated a strong facilitation of the jaw-closing reflex using animals anesthetized with chloralose. Type and depth of anesthesia may have considerable effects on reflex responses; we could assume that they used lightly anesthetized animals. We must also consider a cortical effect on the hypothalamus. Functional and anatomical interactions between the cortex and lateral hypothalamus have been shown by Simonov (1994). The facilitation of MMR may be affected or mediated through cortical activity, and this could be exaggerated in lightly anesthetized or nonanesthetized animals. The larger facilitation of JOR as compared to that of MMR suggests that the connection between the hypothalamus and JOR pathways is much stronger than that between the hypothalamus and jaw-closing reflex pathways. Chi and Flynn (1971) reported that there were two pathways from the hypothalamus to descending structures, and that they might have different roles for animal behavior: affective defense and biting attack. There are some evidence that axon terminals from the hypothalamus associated with quiet biting attack extend to the tegmentum of the rostral pons which could synaptically activate the neighboring trigeminal nucleus (Chi and Flynn, 1971; Landgren and Olsson, 1980). We suggest that the lateral hypothalamus, from which the facilitation of MMR and inhibition of JOR are induced, may be involved in the functional role of quiet biting attack. It remains obscure with regards to the functional role of the lateral portion of the lateral hypothalamus which evoked the facilitation of JOR. However, one could assume that the lateral hypothalamus, from which the facilitation of JOR is induced, may be partly involved in the functional role in affective attack although the site which is responsible for the
affective attack behavior have been known to be located in the medial hypothalamus rather than lateral hypothalamus. Recently Steininger et al. (1999) found REM-on and REM-off neurons in the lateral hypothalamus. We are very interested in those neurons because it is possible that those sleep stage-dependent neurons are part of the population of neurons which have a functional role in the jaw movements as we assume. We expect that we can record lateral hypothalamic neuron activity and discover they are involved in jaw reflexes or oral function in freely behaving animals.
Acknowledgements We thank Dr J. J. A. Scott and Dr H. Crick for helpful comments in corresponding the manuscript.
References Achari, N.K., Thexton, A.J., 1972. Diencephalic influences on the jaw opening reflex in the cat. Arch. Oral Biol. 17, 1073 – 1080. Bobo, E.G., Bonvallet, M., 1975. Amygdala and masseteric reflex. I. Facilitation, inhibition and diphasic modifications of the reflex, induced by localized amygdaloid stimulation. Electroencephalogr. Clin. Neurophysiol. 39, 329 – 339. Brody, J.F., DeFeudis, P.A., DeFeudis, F.V., 1969. Effects of microinjections of L-glutamate into the hypothalamus on attack and flight behaviour in cats. Nature 224, 1330. Brown, J.L., Hunsperger, R.W., Rosvold, H.E., 1969. Defence, attack, and flight elicited by electrical stimulation of the hypothalamus of the cat. Exp. Brain Res. 8, 113 – 129. Chi, C.C., Flynn, J.P., 1971. Neural pathways associated with hypothalamically elicited attach behavior in cats. Science 171, 703 – 706. Hosoya, Y., Matsushita, M., 1981. Brainstem projections from the lateral hypothalamic area in the rat, as studied with autoradiography. Neurosci. Lett. 24, 111 – 116. Inoue, M., Yamamura, K., Nakajima, T., Yamada, Y., 1999. Changes in reflex responses of the masseter and digastric muscles during sleep in freely behaving rabbits. Neurosci. Res. 34, 37 –44. Jurkowlaniec, E., Pracki, T., Trojniar, W., Tokarski, J., 1996. Effect of lateral hypothalamic lesion on sleep-waking pattern and EEG power spectra in the rat. Acta. Neurobiol. Exp. (Warsz.) 56, 249 – 253. King, E.E., Mintz, B., Unna, K.R., 1955. The effect of the brain stem reticular formation on the linguomandibular reflex. J. Comp. Neurol. 102, 565 – 596. Landgren, S., Olsson, K.A., 1980. The effect of electrical stimulation in the hypothalamus on the monosynaptic jaw closing and the disynaptic jaw opening reflexes in the cat. Exp. Brain Res. 39, 389 – 400. Lin, J.S., Sakai, K., Vanni, M.G., Jouvet, M., 1989. A critical role of the posterior hypothalamus in the mechanisms of wakefulness determined by microinjection of muscimol in freely moving cats. Brain Res. 479, 225 – 240. Nagy, J.I., Buss, M., Daddona, P.E., 1986. On the innervation of trigeminal mesencephalic primary afferent neurons by adenosine deaminase-containing projections from the hypothalamus in the rat. Neuroscience 17, 141 – 156.
M. Inoue et al. / Neuroscience Research 41 (2001) 61–65 Ohta, M., 1984. Amygdaloid and cortical facilitation or inhibition of trigeminal motoneurons in the rat. Brain Res. 291, 39 –48. Sawyer, C.H., Everette, J.W., 1954. The rabbit diencephalon in stereotaxic coordinates. J. Comp. Neurol. 101, 801 –824. Semba, K., 1993. Aminergic and cholinergic afferents to REM sleep induction regions of the pontine reticular formation in the rat. J. Comp. Neurol. 330, 543 –556. Simonov, P.V., 1994. Corticohypothalamic relationships during the
65
development and realization of the conditioned reflex. Neurosci. Behav. Physiol. 24, 267 – 273. Steininger, T.L., Alam, M.N., Gong, H., Szymusiak, R., McGinty, D., 1999. Sleep-waking discharge of neurons in the posterior lateral hypothalamus of the albino rat. Brain Res. 840, 138 –147. Szymusiak, R., Iriye, T., McGinty, D., 1989. Sleep-waking discharge of neurons in the posterior lateral hypothalamic area of cats. Brain Res. Bull. 23, 111 – 120.
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Changes in jaw reflexes by stimulation of the hypothalamus in anesthetized rabbits Makoto Inoue a,*, Kayoko Nozawa-Inoue b, Yozo Miyaoka c, Yoshiaki Yamada a a
Di6ision of Oral Physiology, Department of Oral Biological Science, Niigata Uni6ersity Graduate School of Medical and Dental Sciences, Niigata 951 -8514, Japan b Di6ision of Oral Anatomy, Department of Oral Biological Science, Niigata Uni6ersity Graduate School of Medical and Dental Sciences, Niigata 951 -8514, Japan c Department of Health and Nutrition, Niigata Uni6ersity of Health and Welfare, Niigata 950 -3198, Japan Received 9 April 2001; accepted 15 June 2001
Abstract Changes in the masseteric monosynaptic reflex (MMR) and jaw-opening reflex (JOR) responses resulting from conditioning stimulation in the hypothalamus were studied in anesthetized rabbits. Stimulation of the lateral hypothalamus evoked a facilitation of the MMR and an inhibitory or facilitatory effect on the JOR. The facilitatory effect on JOR was stronger than that on the MMR. The facilitatory effective site for the JOR was in the dorsal and lateral directions as compared to the inhibitory field. The results suggest two functionally distinct regions in the lateral hypothalamus that separately project to the jaw-opening muscles. © 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. Keywords: Jaw reflex; Lateral hypothalamus; Electrical stimulation; Rabbit
The authors demonstrated that jaw-closing reflex amplitudes were markedly reduced in active sleep (AS) but it was intermittently and drastically increased during the rapid eye movement (REM) period of AS, and the jaw-opening reflex (JOR) remained inhibited throughout AS (Inoue et al., 1999). These results indicated predominantly a difference in the excitability between the two groups, jaw-closing and jaw-opening muscles, during the REM period. In this paper, we have examined the specific regions in the brain, which may be responsible for the modulation of such jaw reflexes. Electrical stimulation of the hypothalamus induces attack or defense responses in which opening and closing jaws are obvious elements (Brody et al., 1969; Brown et al., 1969; Chi and Flynn, 1971), and modulates jaw reflexes (Achari and Thexton, 1972; Landgren and Olsson, 1980). There are also some evidence that * Corresponding author. Division of Oral Physiology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan. Tel.: +81-25227-2824; fax: +81-25-225-0281. E-mail address: [email protected] (M. Inoue).
the hypothalamic neurons send their axons extensively to descending structures including some nuclei in the vicinity of the trigeminal motor nucleus such as the trigeminal mesencephalic nucleus and nucleus reticularis parvocellularis (Hosoya and Matsushita, 1981; Nagy et al., 1986). Additionally, previous physiological and anatomical studies suggest that the lateral hypothalamus is implicated in control of electroencephalographic desynchrony and arousal action (Jurkowlaniec et al., 1996; Lin et al., 1989; Semba, 1993; Szymusiak et al., 1989). However, the relationship between the hypothalamic jaw movement-related regions and their activities during sleep still remains to be substantiated. Although the final goal of our study is to clarify a physiological interaction between the hypothalamic and trigeminal motor activity, the aim of the present work, as a first step, was to localize the region in the hypothalamus that has modulatory effects on the jaw reflexes, and to evaluate the modulatory response. Twelve male rabbits, weighing between 2.0 and 2.5 kg, were used. They were anesthetized initially with urethane (1.2 g/kg, iv), and anesthesia was maintained with a supplemental dose of urethane (0.1 g/kg/h, iv).
0168-0102/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. PII: S 0 1 6 8 - 0 1 0 2 ( 0 1 ) 0 0 2 6 0 - 7
62
M. Inoue et al. / Neuroscience Research 41 (2001) 61–65
Surgical preparations of the animals were similar to those we reported previously (Inoue, et al., 1999). Briefly, electrodes for electromyographic (EMG) recordings were implanted into the right masseter and digastric muscles. For test stimulations, the trigeminal mesencephalic nucleus was stimulated (three train pulses of 0.1 ms and 2 kHz) to evoke the masseteric monosynaptic reflex response (MMR), and the inferior alveolar nerve was stimulated (three train pulses of 0.1 ms and 2 kHz) to evoke the JOR. The strength of stimulation was set at 1.5 times the threshold for each reflex. For conditioning stimulation, a bipolar needle electrode was inserted into the right hypothalamus by means of Sawyer coordinates (Sawyer and Everette, 1954). These electrodes were moved in steps of 0.5 mm and the hypothalamus was stimulated (five train pulses of 0.2 ms and 2 kHz, 0.2 mA). The interval between the conditioning and test
stimuli (the C–T interval) was varied from 0 to 100 ms in 5 ms steps. Evoked EMGs were recorded and analyzed by means of a computer (Power Mac 5300cs: Apple) and interactive software (MacLab: ADI). We evaluated peak-to-peak amplitudes of the MMR and JOR recorded during each session using the mean amplitude of 20 times recordings, and then normalized individual mean amplitudes to the control MMR and JOR. We evaluated one position as most facilitatory or inhibitory for the jaw reflex activity in one animal if it was effective statistically. Data were analyzed using the analysis of variance and the Tukey’s multiple comparisons test. At the end of experiment, the animals were killed with an overdose of the anesthetic. The brain was removed and tissue sections were subjected to histological preparations to evaluate the location of the electrode tip in the hypothalamus.
Fig. 1. Effects of electrical stimulation in the lateral hypothalamus on the masseteric monosynaptic reflex (MMR) and jaw opening reflex (JOR). In diagram A, changes of normalized values in the MMR are indicated. In diagrams B – C, changes of normalized values in the JOR are indicated. Diagrams D – F indicate sample records averaged in A –C, respectively. Arrows indicate the time of test stimulation. Sample (a) is a control record. Samples (b – f) correspond to points shown in A – C. Diagrams G – H indicate the position of the electrode tip in the hypothalamus ( , , and
) and the effect of each stimulation is shown by the same symbol in A – B, respectively. Diagram I indicates the position of the electrode tip in the hypothalamus ( and ) and the effect of each stimulation is shown by the same symbol in C. Amy, amygdala; IC, internal capsule; FX, fornix; GP, globus pallidus; LHA, lateral hypothalamic area; OT, optic tract; Put, putamen; SO, supraoptic nucleus; IIIV, third ventricle. *PB0.01.
M. Inoue et al. / Neuroscience Research 41 (2001) 61–65 Table 1 Parameters of masseteric monosynaptic reflex (MMR) and jaw-opening reflex (JOR) n
MMR JOR
9 9
Facilitation
Inhibition
n%
Amplitude
n%
Amplitude
3 5
2.19 0.9 10.2 9 4.7
0 5
0.3 9 0.1
n is number of samples tested. n% is number of samples from which modulation was observed. Amplitude represents the normalized value. Each value is mean of means 9 SEM.
Fig. 1(A,D) shows an example of the effect on the MMR of locating the electrode tip in the lateral hypothalamus as shown in Fig. 1(G). A typical effect on the MMR was a small and short facilitation (Fig. 1(A) and Table 1). The C–T interval of this facilitation was B 10 ms. This small facilitatory effect on the MMR was observed only in three out of nine animals, and no effect in the rest. The modulation of JOR was evaluated along with the MMR. Fig. 1(B,E and C,H) shows examples of the effect of stimulating the lateral hypothalamus on the JOR as shown in Fig. 1(H and I), respectively. The typical effect on the JOR was either large facilitation or strong inhibition (Fig. 1(B– C) and Table 1). The facilitatory effect on the JOR (10.29 4.7 times of control) was much larger than the MMR (2.19 0.9 times of control) (Table 1). The C– T interval of the facilitation was 20 ms and that of the inhibition was 30 ms. All these effective sites were consid-
63
erably small and there was no effect on these reflex responses when the stimulating electrodes were moved to other regions. Fig. 2 illustrates histological location of the electrode tip in part of the hypothalamus from which the maximal effects on the MMR and JOR could be evoked in all animals. The effective sites on the MMR were limited to the rostral portion of the lateral hypothalamus and the area just lateral to the fornix. The effective sites on the JOR also appeared to be in the lateral hypothalamus but the area was larger in the lateral and caudal directions than those for the MMR. The electrode tip sites that had facilitatory effects on the JOR seemed to be clustered more dorsally and laterally than those where the inhibitory effects were evoked (Fig. 2). There were no stimulation sites that simultaneously affected amplitudes of MMR and JOR. Present data showed that a facilitatory effect on the MMR was small as compared to data shown by Landgren and Olsson (1980) (\10 times of control) and it was observed only in three out of nine animals. In addition, we observed not only an inhibitory but also a facilitatory effect on the JOR. Facilitation of the JOR was much stronger than that of the MMR in our data (compare Fig. 1(A–B)). To interpret these results, we must consider the possibility of whether it was cell bodies in the lateral hypothalamus which were excited or axons from other structures passing through the hypothalamus. Several pathways which were activated can affect the JOR through the region near the lateral hypothalamus. King et al. (1955) reported facilitation of the JOR following
Fig. 2. These diagrams show the location in the lateral hypothalamus of the electrode tip. Facilitation of the masseteric monosynaptic reflex (MMR) ( ), facilitation of the jaw opening reflex (JOR) ( ) and inhibition of the JOR () were observed after the hypothalamus was stimulated. These sites had the maximal effects on the MMR and JOR. Amy, amygdala; C, caudate nucleus; IC, internal capsule; FX, fornix; GP, globus pallidus; LHA, lateral hypothalamic area; OT, optic tract; Put, putamen; SO, supraoptic nucleus; IIIV, third ventricle.
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M. Inoue et al. / Neuroscience Research 41 (2001) 61–65
the stimulation of the pathway from the motor cortex and caudate to the reticular formation. Furthermore, electrical stimulation of the amygdala has known to modulate jaw muscle activity (Bobo and Bonvallet, 1975; Ohta, 1984). It is possible that we might have stimulated a part of them. However, the intensity of stimulus used by King et al. (2– 4 mA) was much higher than that used in this study (0.2 mA) and we never found any other modulation of jaw reflexes when electrodes were moved to other sites. Therefore, it is unlikely that we evoked axon activity in such descending pathways. The stimulus condition used by Landgren and Olsson (1980) (10 pulses, 0.5 ms and 0.5 mA) to facilitate the MMR was also higher than present data. This stimulation might lead to a large facilitation of MMR as compared to our results. The present results did not indicate a large facilitation of masseter muscle activity following the stimulation of the lateral hypothalamus, suggesting that this area is not responsible for the drastic change of excitability in masseter muscle during sleep. Landgren and Olsson (1980) demonstrated a strong facilitation of the jaw-closing reflex using animals anesthetized with chloralose. Type and depth of anesthesia may have considerable effects on reflex responses; we could assume that they used lightly anesthetized animals. We must also consider a cortical effect on the hypothalamus. Functional and anatomical interactions between the cortex and lateral hypothalamus have been shown by Simonov (1994). The facilitation of MMR may be affected or mediated through cortical activity, and this could be exaggerated in lightly anesthetized or nonanesthetized animals. The larger facilitation of JOR as compared to that of MMR suggests that the connection between the hypothalamus and JOR pathways is much stronger than that between the hypothalamus and jaw-closing reflex pathways. Chi and Flynn (1971) reported that there were two pathways from the hypothalamus to descending structures, and that they might have different roles for animal behavior: affective defense and biting attack. There are some evidence that axon terminals from the hypothalamus associated with quiet biting attack extend to the tegmentum of the rostral pons which could synaptically activate the neighboring trigeminal nucleus (Chi and Flynn, 1971; Landgren and Olsson, 1980). We suggest that the lateral hypothalamus, from which the facilitation of MMR and inhibition of JOR are induced, may be involved in the functional role of quiet biting attack. It remains obscure with regards to the functional role of the lateral portion of the lateral hypothalamus which evoked the facilitation of JOR. However, one could assume that the lateral hypothalamus, from which the facilitation of JOR is induced, may be partly involved in the functional role in affective attack although the site which is responsible for the
affective attack behavior have been known to be located in the medial hypothalamus rather than lateral hypothalamus. Recently Steininger et al. (1999) found REM-on and REM-off neurons in the lateral hypothalamus. We are very interested in those neurons because it is possible that those sleep stage-dependent neurons are part of the population of neurons which have a functional role in the jaw movements as we assume. We expect that we can record lateral hypothalamic neuron activity and discover they are involved in jaw reflexes or oral function in freely behaving animals.
Acknowledgements We thank Dr J. J. A. Scott and Dr H. Crick for helpful comments in corresponding the manuscript.
References Achari, N.K., Thexton, A.J., 1972. Diencephalic influences on the jaw opening reflex in the cat. Arch. Oral Biol. 17, 1073 – 1080. Bobo, E.G., Bonvallet, M., 1975. Amygdala and masseteric reflex. I. Facilitation, inhibition and diphasic modifications of the reflex, induced by localized amygdaloid stimulation. Electroencephalogr. Clin. Neurophysiol. 39, 329 – 339. Brody, J.F., DeFeudis, P.A., DeFeudis, F.V., 1969. Effects of microinjections of L-glutamate into the hypothalamus on attack and flight behaviour in cats. Nature 224, 1330. Brown, J.L., Hunsperger, R.W., Rosvold, H.E., 1969. Defence, attack, and flight elicited by electrical stimulation of the hypothalamus of the cat. Exp. Brain Res. 8, 113 – 129. Chi, C.C., Flynn, J.P., 1971. Neural pathways associated with hypothalamically elicited attach behavior in cats. Science 171, 703 – 706. Hosoya, Y., Matsushita, M., 1981. Brainstem projections from the lateral hypothalamic area in the rat, as studied with autoradiography. Neurosci. Lett. 24, 111 – 116. Inoue, M., Yamamura, K., Nakajima, T., Yamada, Y., 1999. Changes in reflex responses of the masseter and digastric muscles during sleep in freely behaving rabbits. Neurosci. Res. 34, 37 –44. Jurkowlaniec, E., Pracki, T., Trojniar, W., Tokarski, J., 1996. Effect of lateral hypothalamic lesion on sleep-waking pattern and EEG power spectra in the rat. Acta. Neurobiol. Exp. (Warsz.) 56, 249 – 253. King, E.E., Mintz, B., Unna, K.R., 1955. The effect of the brain stem reticular formation on the linguomandibular reflex. J. Comp. Neurol. 102, 565 – 596. Landgren, S., Olsson, K.A., 1980. The effect of electrical stimulation in the hypothalamus on the monosynaptic jaw closing and the disynaptic jaw opening reflexes in the cat. Exp. Brain Res. 39, 389 – 400. Lin, J.S., Sakai, K., Vanni, M.G., Jouvet, M., 1989. A critical role of the posterior hypothalamus in the mechanisms of wakefulness determined by microinjection of muscimol in freely moving cats. Brain Res. 479, 225 – 240. Nagy, J.I., Buss, M., Daddona, P.E., 1986. On the innervation of trigeminal mesencephalic primary afferent neurons by adenosine deaminase-containing projections from the hypothalamus in the rat. Neuroscience 17, 141 – 156.
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