Neural Circuits Containing Pallidotegmental GABAergic Neurons are Involved in the Prepulse Inhibition of the Startle Reflex in Mice

Kenji Takahashi, Taku Nagai, Hiroyuki Kamei, Kenji Maeda, Takahiro Matsuya, Sawako Arai, Hiroyuki Mizoguchi, Yukio Yoneda, Toshitaka Nabeshima, Kazuhiro Takuma, Kiyofumi Yamada

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Abstract

Background: Prepulse inhibition (PPI) of the startle response is a measure of the inhibitory function and time-linked information processing by which a weak sensory stimulus (the prepulse) inhibits the startle response caused by a sudden intense stimulus. We attempted to clarify the neuronal circuits underlying the control of PPI of the startle reflex in mice. Methods: c-Fos immunohistochemistry was used to detect neurons activated by startle pulse and/or prepulse trials. Behavioural pharmacology and tracing studies were also conducted. Results: The lateral globus pallidus (LGP) was activated by prepulses. Activation of the caudal pontine reticular nucleus (PnC) evoked by the startle pulses was inhibited under PPI conditions. Double-immunostaining revealed that c-Fos-positive cells in the LGP following prepulse trials were GABAergic neurons. Bilateral microinjections of lidocaine into the LGP resulted in an impairment of PPI. Fluoro-gold infusion into the PnC and the pedunculopontine tegmental nucleus (PPTg) retrogradely labeled neurons in the PPTg and LGP, respectively. Microinjections of phaclofen into the PPTg significantly impaired PPI. Conclusions: These results suggest that GABAergic neurons in the LGP which project to the PPTg play a crucial role through the activation of GABAB receptors in the regulation of PPI of the startle reflex in mice.

Original languageEnglish
Pages (from-to)148-157
Number of pages10
JournalBiological Psychiatry
Volume62
Issue number2
DOIs
Publication statusPublished - 15-07-2007

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Startle Reflex
GABAergic Neurons
Pedunculopontine Tegmental Nucleus
Globus Pallidus
Microinjections
Neurons
Lidocaine
Automatic Data Processing
Prepulse Inhibition
Immunohistochemistry
Pharmacology

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry

Cite this

Takahashi, Kenji ; Nagai, Taku ; Kamei, Hiroyuki ; Maeda, Kenji ; Matsuya, Takahiro ; Arai, Sawako ; Mizoguchi, Hiroyuki ; Yoneda, Yukio ; Nabeshima, Toshitaka ; Takuma, Kazuhiro ; Yamada, Kiyofumi. / Neural Circuits Containing Pallidotegmental GABAergic Neurons are Involved in the Prepulse Inhibition of the Startle Reflex in Mice. In: Biological Psychiatry. 2007 ; Vol. 62, No. 2. pp. 148-157.
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abstract = "Background: Prepulse inhibition (PPI) of the startle response is a measure of the inhibitory function and time-linked information processing by which a weak sensory stimulus (the prepulse) inhibits the startle response caused by a sudden intense stimulus. We attempted to clarify the neuronal circuits underlying the control of PPI of the startle reflex in mice. Methods: c-Fos immunohistochemistry was used to detect neurons activated by startle pulse and/or prepulse trials. Behavioural pharmacology and tracing studies were also conducted. Results: The lateral globus pallidus (LGP) was activated by prepulses. Activation of the caudal pontine reticular nucleus (PnC) evoked by the startle pulses was inhibited under PPI conditions. Double-immunostaining revealed that c-Fos-positive cells in the LGP following prepulse trials were GABAergic neurons. Bilateral microinjections of lidocaine into the LGP resulted in an impairment of PPI. Fluoro-gold infusion into the PnC and the pedunculopontine tegmental nucleus (PPTg) retrogradely labeled neurons in the PPTg and LGP, respectively. Microinjections of phaclofen into the PPTg significantly impaired PPI. Conclusions: These results suggest that GABAergic neurons in the LGP which project to the PPTg play a crucial role through the activation of GABAB receptors in the regulation of PPI of the startle reflex in mice.",
author = "Kenji Takahashi and Taku Nagai and Hiroyuki Kamei and Kenji Maeda and Takahiro Matsuya and Sawako Arai and Hiroyuki Mizoguchi and Yukio Yoneda and Toshitaka Nabeshima and Kazuhiro Takuma and Kiyofumi Yamada",
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Takahashi, K, Nagai, T, Kamei, H, Maeda, K, Matsuya, T, Arai, S, Mizoguchi, H, Yoneda, Y, Nabeshima, T, Takuma, K & Yamada, K 2007, 'Neural Circuits Containing Pallidotegmental GABAergic Neurons are Involved in the Prepulse Inhibition of the Startle Reflex in Mice', Biological Psychiatry, vol. 62, no. 2, pp. 148-157. https://doi.org/10.1016/j.biopsych.2006.06.035

Neural Circuits Containing Pallidotegmental GABAergic Neurons are Involved in the Prepulse Inhibition of the Startle Reflex in Mice. / Takahashi, Kenji; Nagai, Taku; Kamei, Hiroyuki; Maeda, Kenji; Matsuya, Takahiro; Arai, Sawako; Mizoguchi, Hiroyuki; Yoneda, Yukio; Nabeshima, Toshitaka; Takuma, Kazuhiro; Yamada, Kiyofumi.

In: Biological Psychiatry, Vol. 62, No. 2, 15.07.2007, p. 148-157.

Research output: Contribution to journalArticle

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T1 - Neural Circuits Containing Pallidotegmental GABAergic Neurons are Involved in the Prepulse Inhibition of the Startle Reflex in Mice

AU - Takahashi, Kenji

AU - Nagai, Taku

AU - Kamei, Hiroyuki

AU - Maeda, Kenji

AU - Matsuya, Takahiro

AU - Arai, Sawako

AU - Mizoguchi, Hiroyuki

AU - Yoneda, Yukio

AU - Nabeshima, Toshitaka

AU - Takuma, Kazuhiro

AU - Yamada, Kiyofumi

PY - 2007/7/15

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N2 - Background: Prepulse inhibition (PPI) of the startle response is a measure of the inhibitory function and time-linked information processing by which a weak sensory stimulus (the prepulse) inhibits the startle response caused by a sudden intense stimulus. We attempted to clarify the neuronal circuits underlying the control of PPI of the startle reflex in mice. Methods: c-Fos immunohistochemistry was used to detect neurons activated by startle pulse and/or prepulse trials. Behavioural pharmacology and tracing studies were also conducted. Results: The lateral globus pallidus (LGP) was activated by prepulses. Activation of the caudal pontine reticular nucleus (PnC) evoked by the startle pulses was inhibited under PPI conditions. Double-immunostaining revealed that c-Fos-positive cells in the LGP following prepulse trials were GABAergic neurons. Bilateral microinjections of lidocaine into the LGP resulted in an impairment of PPI. Fluoro-gold infusion into the PnC and the pedunculopontine tegmental nucleus (PPTg) retrogradely labeled neurons in the PPTg and LGP, respectively. Microinjections of phaclofen into the PPTg significantly impaired PPI. Conclusions: These results suggest that GABAergic neurons in the LGP which project to the PPTg play a crucial role through the activation of GABAB receptors in the regulation of PPI of the startle reflex in mice.

AB - Background: Prepulse inhibition (PPI) of the startle response is a measure of the inhibitory function and time-linked information processing by which a weak sensory stimulus (the prepulse) inhibits the startle response caused by a sudden intense stimulus. We attempted to clarify the neuronal circuits underlying the control of PPI of the startle reflex in mice. Methods: c-Fos immunohistochemistry was used to detect neurons activated by startle pulse and/or prepulse trials. Behavioural pharmacology and tracing studies were also conducted. Results: The lateral globus pallidus (LGP) was activated by prepulses. Activation of the caudal pontine reticular nucleus (PnC) evoked by the startle pulses was inhibited under PPI conditions. Double-immunostaining revealed that c-Fos-positive cells in the LGP following prepulse trials were GABAergic neurons. Bilateral microinjections of lidocaine into the LGP resulted in an impairment of PPI. Fluoro-gold infusion into the PnC and the pedunculopontine tegmental nucleus (PPTg) retrogradely labeled neurons in the PPTg and LGP, respectively. Microinjections of phaclofen into the PPTg significantly impaired PPI. Conclusions: These results suggest that GABAergic neurons in the LGP which project to the PPTg play a crucial role through the activation of GABAB receptors in the regulation of PPI of the startle reflex in mice.

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