Chewing ameliorates stress-suppressed hippocampal CA1-LTP via activation of histamine H1 receptor

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Abstracts

(MBs). Since the MBs are considers to be the memory center, there is an intriguing possibility that the ap gene participates in Drosophila memory. To examine this possibility, we used the courtship conditioning assay and investigated if any memory defects are observed in ap mutants. The courtship conditioning is an associative learning paradigm, where male courtship behavior is suppressed by experience with recently mated unreceptive females. Four ap mutants showed normal short-lasting memory induced by courtship conditioning. However, all mutants showed the defective long-term memory. In addition, induction of ap RNAi in the MBs after eclosion induced the defective long-term memory. These results suggest that ap expression in the MBs is required for long-term courtship memory. doi:10.1016/j.neures.2009.09.1010

a cross-correlation analysis between DA and locomotion, and discuss the fundamental roles of DA transmission in the prefrontal cortex with respect to navigation control. doi:10.1016/j.neures.2009.09.1013

P2-m19 pathway: Wakoto Hiroyuki Kaneko 2

Axonal arborization of mesocorticolimbic dopaminergic a single-cell study Matsuda 1 , Takahiro Furuta 2 , Kouichi Nakamura 2 , 2 2 Hioki , Fumino Fujiyama , Osamu Yasuhara 1 , Takeshi

1

P2-m16 Learning/memory impairment and reduced expression of the HNK-1 carbohydrate in ␤-1,4-Galactosyltransferase-II-deficient mice Toru Yoshihara 1,2 , Kazushi Sugihara 2 , Yasuhiko Kiduka 3 , Shogo Oka 4 , Masahide Asano 2 1

Kanazawa University Res. Ctr. Child Mental Develop., Japan; 2 Adv. Sci. Res. Ctr, Kanazawa University, Japan; 3 Grad. Sch. Pharm. Sci., Kyoto University, Japan; 4 Grad. Sch. Med., Kyoto University, Japan

␤-1,4-Galactosyltransferase-II (␤4-GalT-II), one of seven ␤4-GalT family genes, is a glycosyltransferase that is involved in the biosynthesis of type 2 backbone structure (Gal␤1 → 4GlcNAc). In mouse brain, ␤4-GalT-II is prominently expressed from early embryonic stages and thought to have critical roles in the brain organization, cognitive function, etc. We have generated ␤4-GalT-II-deficient mice and tested multiple behavioral tasks. As results, the locomotor activity of knock out (KO) mice was almost normal, but they were impaired in spatial learning/memory and motor coordination that observed in the Morris water maze task and rota-rod test, respectively. Histological analyses further showed abnormal alignment and reduced number of Purkinje cells in the cerebellum of the KO mice. In the hippocampus, the HNK-1 carbohydrate, which has a sulfated glucuronic acid at the non-reducing terminus of carbohydrates, was drastically reduced. doi:10.1016/j.neures.2009.09.1011

P2-m17 Downregulation of Fyn tyrosine kinase activity in the mouse dorsal hippocampus facilitates extinction of conditioned fear Tomoko Isosaka 1 , Satoshi Kida 2 , Shigeki Yuasa 1 1 Department Ultrastructural Res., Nat. Inst. of Neurosci., NCNP, Tokyo, Japan; 2 Department Biosci., Tokyo University of Agriculture, Tokyo, Japan

In contextual fear conditioning, a mouse is placed in a training cage and a foot shock is delivered, so that the mouse associates the context with the shock. When the mouse is returned to the context, contextual memory can be measured as the degree of freezing behavior. Fear extinction occurs when mice are re-exposed to the context without receiving the foot shock again, and it can be determined as the decline of freezing behavior. Here, we show that Fyn-tyrosine-kinase is involved in the extinction learning. To investigate the role of Fyn in fear extinction, we inhibited Fyn activity in the dorsal hippocampus by stereotaxic injection of PP2 and found the facilitation of fear extinction. We then examined biochemically the dorsal hippocampal tissue, and found that Fyn activity is downregulated following the extinction training. These findings suggest that downregulation of Fyn activity accelerates the extinction of conditioned fear. doi:10.1016/j.neures.2009.09.1012

Shiga University of Medical Science, Japan; Sch Med, Kyoto Univ, Kyoto, Japan

2

Dept Morphol Brain Sci, Grad

Dopaminergic neurons in the substantia nigra compacta and ventral tegmental area (VTA) mediate a variety of brain functions, such as motor control, emotion, and reward. We studied the axonal arborization of VTA neurons with Sindbis virus vectors that expressed membrane-targeted green fluorescent protein (GFP). After injections of the viral vectors into rat VTA, infected single neurons were first examined their TH immunoreactivity and were then visualized completely by the inimmunoperoxidase method with an anti-GFP antibody. After the reconstruction of projection axons, some neurons in VTA were observed to project their axons to the limbic cortices. Another neurons sent axons to the olfactory tubercle, accumbens nucleus, and/or caudate-putamen. Many of these neurons were observed to form high-dense bushes in their terminal fields. Thus, the present study revealed a difference in the axonal ramifications of single dopaminergic neurons. doi:10.1016/j.neures.2009.09.1014

P2-m20 mGluR1 is essential for acquisition but not for expression or retention in eyeblink conditioning Harumi Nakao 1 , Yasushi Kishimoto 2 , Kouichi Hashimoto 3,4 , Kazuki Nakao 5 , Masanobu Kano 3 , Yutaka Kirino 2 , Atsu Aiba 1 1

Div Mol Genet, Kobe Univ Grad Sch Med, Kobe, Japan; 2 Dept NeuroBiophys, Sch Pharamaceut Sci at Kagawa Campus, Tokushima Bunri Univ, Sanuki, Japan; 3 Dept Neurophysiol, Univ Tokyo Grad Sch Med, Tokyo, Japan; 4 CREST, Japan; 5 LARGE, CDB, RIKEN, Kobe, Japan Eyeblink conditioning is a simple form of associative motor learning. Multiple learning processes are involved in the classical conditioning, at least acquisition, expression, and retention of memory. It is known that both cortex and deep nucleus in the cerebellum are important for the eyeblink conditioning, however, contributions of these cerebellar regions in distinct learning processes remain poorly understood. Purkinje cells in the cerebellar cortex abundantly express a subtype 1 of mGluRs (mGluR1) and mGluR1 KO mice exhibited impairment in eyeblink conditioning. Using mGluR1 conditional KO mice reversibly expressing mGluR1 in Purkinje cells, we found that mGluR1 was required for acquisition but not for expression or retention of conditioned eyeblink responses. This result suggests that cerebellar cortex is essential for the memory formation. doi:10.1016/j.neures.2009.09.1015

P2-n01 Chewing ameliorates stress-suppressed hippocampal CA1LTP via activation of histamine H1 receptor Yumie Ono 1 , Tsuyoshi Kataoka 2 , Shinjiro Miyake 2 , Kenichi 2 2 1 Sasaguri , Sadao Sato , Minoru Onozuka 1

P2-m18 Influence of footshock on the prefrontal dopamine transmission during exploration Masatoshi Takita National Institute of Advanced Industrial Science & Technology (AIST), Japan Either the exploration of a novel environment or the stress can stimulate dopamine (DA) transmission in the rat medial prefrontal cortex (mPFC). We investigated the mutual interaction between exploration-derived and stress-derived DA through simultaneous measurements of exploratory locomotion in an open-field cage (45 cm square, equipped with shock grids) and mPFC DA using a high-performance liquid chromatography with electrochemical detection (HPLC-ECD) microdialysis method, twice, 24 hr apart while the rats were kept in their home cage except during measurement periods. The effect of the footshock (0, 0.3, or 1.0 mA) was tested at the first measurement and the DA release was higher in the 1.0-mA group than in the others. The basal DA level before the second exploration was higher than that before the first exploration in the 1.0-mA group, as compared to the 0 or 0.3-mA groups. We performed an autocorrelation analysis of either DA or locomotion and

Department Physiol. and Neurosci. Kanagawa Dent. Col., Kanagawa, Japan; 2 Department Ortho. Kanagawa Dent. Col., Kanagawa, Japan We studied the involvement of the histaminergic system, which has been shown to be activated by mastication, in the long-term potentiation (LTP) of hippocampal slices of rats that were allowed to chew a wooden stick during exposure to immobilization stress. Chewing failed to rescue stress-suppressed LTP in the rats treated with histamine H1 receptor antagonist pyrilamine (5 mg/kg, i.p.) before exposure to stress, although administration of pyrilamine did not affect LTP in naive rats and in stressed rats that did not chew. However, when pyrilamine was administrated immediately after exposure to stress, chewing rescued LTP whose magnitude was statistically comparable to that in the rats that chewed without drug treatment. These results suggest that chewing-induced histamine release in the hippocampus and the subsequent H1 receptor activation may be essential to rescue stress-suppressed synaptic plasticity. doi:10.1016/j.neures.2009.09.1016