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The Journal of Neuroscience, February 1, 1999, 19(3):955-963
Metabotropic Glutamate Receptor Subtype 7 Ablation Causes Deficit
in Fear Response and Conditioned Taste Aversion
Miwako
Masugi1,
Mineto
Yokoi1,
Ryuichi
Shigemoto2,
Keiko
Muguruma3,
Yasuyoshi
Watanabe3,
Gilles
Sansig4,
Herman
van der
Putten4, and
Shigetada
Nakanishi1
Departments of 1 Biological Sciences and
2 Morphological Brain Science, Kyoto University Faculty of
Medicine, Kyoto 606-8501, Japan, 3 Department of
Neuroscience, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan,
and 4 Novartis Pharma AG, Nervous System Department,
CH-4002 Basel, Switzerland
Metabotropic glutamate receptors (mGluRs) consist of eight
different subtypes and exert their effects on second messengers and ion
channels via G-proteins. The function of individual mGluR subtypes in
the CNS, however, largely remains to be clarified. We examined the fear
response of freezing after electric shock in wild-type and
mGluR7 / knockout littermates. Wild-type mice
displayed freezing immediately after and 1 d after footshock. In
comparison, mGluR7/ knockout mice showed
significantly reduced levels in both immediate postshock and delayed
freezing responses. However, the knockout mice exhibited no
abnormalities in pain sensitivity and locomotor activity. To further
examine amygdala-dependent behavior, we performed conditioned taste
aversion (CTA) experiments. In wild-type mice, the administration of
saccharin followed by intraperitoneal injection of the malaise-inducing
agent LiCl resulted in an association between saccharin and LiCl. This
association caused strong CTA toward saccharin. In contrast,
mGluR7/ knockout mice failed to associate
between the taste and the negative reinforcer in CTA experiments.
Again, the knockout mice showed no abnormalities in taste preference
and in the sensitivity to LiCl toxicity. These results indicate that
mGluR7 deficiency causes an impairment of two distinct
amygdala-dependent behavioral paradigms. Immunohistochemical and
immunoelectron-microscopic analyses showed that mGluR7 is highly
expressed in amygdala and preferentially localized at the
presynaptic axon terminals of glutamatergic neurons. Together, these
findings strongly suggest that mGluR7 is involved in neural processes
subserving amygdala-dependent averse responses.
Key words:
metabotropic glutamate receptor subtype 7; knockout mice; presynaptic receptor; fear response; conditioned taste aversion; amygdala
Copyright © 1999 Society for Neuroscience 0270-6474/99/193955-09$05.00/0
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