Striatal dopamine D1 receptor is essential for contextual fear conditioning

Masayoshi Mishina1,2, Masaru Ikegami2, Takeshi Uemura2, Ayumi Kishioka2 and Kenji Sakimura3

1Brain Science Laboratory, The Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga, Japan
2Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
3Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan

Fear is an adaptive component of response to potentially threatening stimuli, serving a function that is critical to the survival of higher vertebrates. On the other hand, too much or inappropriate fear accounts for many common psychiatric problems. Numerous studies have shown that the amygdala, hippocampus and medial prefrontal cortex play important roles in Pavlovian fear conditioning. Recently, we showed that striatal neurons are required for the formation of the auditory fear memory when the unconditioned stimulus is weak. Here, we found that selective ablation of striatal neurons strongly diminished contextual fear conditioning irrespective of the intensity of footshock. Furthermore, contextual fear conditioning was strongly reduced in striatum-specific dopamine D1 receptor knockout mice. On the other hand, striatum-specific dopamine D2 receptor knockout mice showed freezing responses comparable to those of control mice. These results suggest that striatal D1 receptor is essential for contextual fear conditioning.