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404 Abstracts / Neuroscience R

3-l13 Neuronal coding of rewarding and aversive stimulin the primate dorsal raphe nucleusazuko Hayashi 1 , Kazuko Nakao 1, Ken-ichi Okada 2, Yasushiobayashi 2,3,4, Kae Nakamura 1,3,4

Department of Physiology, Kansai Medical University, Osaka 2 Graduatechool of Frontier Biosciences, Osaka University, Osaka 3 ATR Computationaleuroscience Laboratories, Kyoto 4 PRESTO, JST

euronal activity in the dorsal raphé nucleus (DRN), a major source of sero-onin, is modulated by the received reward size. To investigate whether DRNeurons code rewarding or aversive stimuli and/or positive or negative pre-iction error, we recorded single-unit activity in the DRN of two monkeyserforming the trace conditioning task. This task consisted of two blocksith distinct contexts. In the appetitive block, liquid reward was used as annconditioned stimulus (US). In the aversive block, air-puff directed at theonkey face was used as a negative US. In both blocks, three visual stimuli

conditioned stimuli: CSs) were paired with the US, with probabilities of 100,0 and 0%, respectively. To confirm that monkeys learned the association ofach specific CS with the US, we monitored licking behavior and anticipatoryye blinking. In 50 and 0% trials, tone was presented as a neutral stimulus inhe absence of reward or air-puff.

e recorded 211 task-related neurons. It was found that DRN neuronsesponded to the CSs in the appetitive block more often than in the aversivelock; 38% (n = 81) responded to the rewarding CS with 100% probability,hile 9% (n = 19) responded to the aversive CS with 100% probability. Among

hem, 13 neurons responded to both rewarding and aversive CSs. Many DRNeurons also responded to the USs (n = 176); either to reward only (n = 35),o air-puff only (n = 57) or to both (n = 84). In the appetitive block, reward-elated activity was modulated by its probability with stronger response tohe unpredicted than the predicted US. In the aversive block, short-latencyesponse to air-puff delivery was frequently observed regardless of the CS-USredictability. These results suggest that the primate DRN codes informationbout both rewarding and aversive stimuli, and some DRN neurons exhibitedctivity similar to reward prediction error reported for dopamine neurons.

oi:10.1016/j.neures.2010.07.1791

3-l14 Impairment of classical fear conditioning by localnesthesia of the cerebellum in goldfishasayuki Yoshida , Ruriko Hirano

Graduate School of Biosphere Science, Hiroshima University, Higashihi-oshima, Japan

he cerebellum, besides the amygdala, has been demonstrated to play amportant role in simple classical fear conditioning in both mammals andshes. In the present study, we examined the effect of the functional lesion ofhe cerebellum by a local administration of the anesthetic agent lidocaine onear-related, classical heart-rate conditioning in goldfish. The fear condition-ng paradigm was delayed classical conditioning with light as a conditionedtimulus and electric shock as an unconditioned stimulus; cardiac deceler-tion (bradycardia) was the conditioned response. Lidocaine was injectedsing a microinjector through a fine needle kept inserted in the cerebellarorpus. Injecting lidocaine into the cerebellum had no effect on the baseeart rate. An arousal/orienting response to the first presentation of lighti.e., a novel stimulus for the subject) was not affected by lidocaine injection,ndicating that the sensory pathway mediating the visual stimulus was keptntact in lidocaine-injected fish. On the other hand, lidocaine injection greatlympaired acquisition of conditioned bradycardia. Since lidocaine-injectedsh showed an unconditioned response to the electric shock, failure in acqui-ition of the conditioned bradycardia in lidocaine-injected fish was not dueo sensory disruption or impairment in the center directly regulating heartate. Lidocaine injection 60 min before the start of the conditioning proce-ure showed no effect on acquisition of conditioned bradycardia, indicating

hat the effect of lidocaine was reversible. The present results further con-rm the idea that the cerebellum in teleost fish, as in mammals, is critically

nvolved in classical fear conditioning.

oi:10.1016/j.neures.2010.07.1792

ch 68S (2010) e335–e446

P3-l15 Noradrenergic neurons are activated depending onthe difficulty of decision-making in ratSeiichiro Amemiya , Natsuko Kubota, Tomomi Otsuka, ChiharuMotoki, Takeshi Nishijima, Ichiro KitaGuraduate school of human health science, Tokyo Metropolitan university,Tokyo, Japan

In difficult choice situation, there are higher demands for exploration andassessment of preferences for optimal decision-making. Previous studiesreported that activity of noradrenergic neuron in locus coeruleus (LC) mod-ulates exploration state, in which subjects search for behaviors fitting to taskrules. Furthermore, �2 receptor antagonist, idazoxan, which increases therelease of noradrenaline (NA), facilitates attentional shift and consequentlyguides rapid optimization of behavior in appetitive tasks. Therefore, wehypothesize that the more difficult a choice condition is, the more noradren-ergic neurons are activated for optimization of choice behavior. To examinethis hypothesis, we examined performances of T-maze two-alternativechoice task in different difficulties and activation of noradrenergic neuronin LC by double-labeling immunohistochemistry in rats. We manipulatedthe degree of discriminability between choices by varying the differenceof amounts of reward pellets between two arms (0 vs 4, 1 vs 3, 2 vs 2).The data showed that as the discriminability diminished, choice bias to oneside arm was reduced and time to enter one of two arms was prolonged,indicating that difficulty of the task could relate to the discriminability, thatis, difficulty is the highest in 2vs2 condition. In terms of neuronal activity, weobserved that noradrenergic neurons are activated depending on decreasingof the discriminability, that is, 2vs2 condition showed the highest activationof noradrenergic neurons. These results suggest that noradrenalinergicneurons in LC have a role for optimal decision-making.

doi:10.1016/j.neures.2010.07.1793

P3-l16 Developmental effects of one-carbon nutrients-deficient diet on anxiety and fearDaisuke Ishii , Daisuke Matsuzawa, Chihiro Sutoh, ShingoMatsuda, Haruna Tomizawa, Eiji ShimizuDepartment of Cognitive Behavioral Physiology, Chiba University GraduateSchool of Medicine

Nutrients related to one-carbon metabolism is known to play importantroles in the maintenance of genomic DNA methylation. Previous studieshave shown that dietary deficiency in folate, choline and methionine causedglobal DNA hypermethylation in the brain. In the present study, we exam-ined behavioral alterations in mice after developmental dietary deficiency inessential one-carbon nutrients. We found that a developmental one-carbonnutrients-deficient diet caused an increased anxiety, and an enhanced acqui-sition and extinction of the contextual fear memory. Our data suggestedthat the one-carbon metabolic pathway in the developmental brain may beassociated with an increased anxiety and an enhanced fear memory.

doi:10.1016/j.neures.2010.07.1794

P3-l17 Histological and behavioral analyses inCL3/CaMKIgamma-deficient miceSayaka Takemoto-Kimura 1 , Satoshi Kamijo 1, ShinichiroHorigane 1, Kanzo Suzuki 1, Hiroyuki Okuno 1, Asahi Haijima 2,Toshihiro Endo 2, Tomonori Takeuchi 3, Manabu Abe 4, RieNatsume 4, Maya Yamazaki 4, Hisashi Mori 3, Chiharu Tohyama 2,Kenji Sakimura 4, Masayoshi Mishina 3, Masaki Kakeyama 2,Haruhiko Bito 1

1 Department of Neurochem, Grad. Sch. of Med., University Tokyo, Tokyo2 Div. Environmental Health Sciences, Center for Disease Biology and Inte-grative Medicine, Grad Sch of Med, Univ Tokyo, Tokyo 3 Dept MolecularNeurobiology and Pharmacology, Grad. Sch. of Med., University Tokyo, Tokyo4 Department Cellular Neurobiology, Brain Research Institute, Niigata Uni-versity, Niigata

Ca2+/calmodulin-dependent protein kinases (commonly called CaM kinasesor CaMKs) represent major enzymatic targets for an activated Ca2+/ calmod-

ulin (CaM) complex that is generated by intracellular calcium rise. Wepreviously found that distinct limbs of the CaMKK-CaMKI cascade werespecifically implicated in determining the extent of either dendritic or axonalgrowth downstream of different growth/guidance signals in cultured corticalneurons: a membrane anchored isoform of CL3/CaMKIgamma regulated den-