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Abstracts / Neuroscience R

oding neurons. Neurons whose phasic or tonic response to the CS presenta-ion was positively correlated with the reward probability were classified astimulus value coding neurons. Neurons whose activity increased before theelivery of an expected reward were classified as reward expectation codingeurons. We then examined sensitivity to time discounting for these neuronsy increasing the duration of the delay period. With increasing delay, the CSesponse decreased and the reward response increased in the RPE codingeurons, which may be due to an increase of unpredictability of the reward;he CS response decreased in the stimulus value coding neurons, which maye due to a decrease of the stimulus value, and the activity decreased and

ts peak latency shifted toward the new time of the reward delivery in theeward expectation coding neurons, which may be due to the animal’s adap-ation to the new time of the reward delivery. These results suggest that theS, delay, and reward-related activities of striatal neurons can be affected byime discounting.

oi:10.1016/j.neures.2011.07.1636

4-m19 Cognitive control of response inhibition in the pri-ate

azuko Hayashi 1 , Atsushi Noritake 1, Kae Nakamura 1,2

Department of Physiology, Kansai Medical University, Osaka, JapanPRESTO, JST

he dorsal raphé nucleus (DRN) is a major source of serotonin. Many studiesuggest that serotonergic neurotransmission is involved in emotional, cog-itive and behavioral control processes. We have previously shown that therimate DRN neurons code both rewarding and aversive information duringavlovian conditioning task. To further investigate the role of DRN in behav-oral impulsivity, especially regulation of response inhibition, we used anperant conditioning procedure.n this study, a monkey (Macaca fascicularis) was trained using Go/No-goaradigm. On each trial, a fixation point appeared at the center of the screen.fter the fixation, a cue was presented to the left or right of the fixation point.ach cue was associated with different action (Go/No-go). If the cue indicatedGo”, the monkey made saccade to the left or right. If “No-go”, the monkeyad to inhibit saccade to the target and continue to gaze at the central fix-tion point. A liquid reward was delivered after the appropriate generationr inhibition of saccade. The monkey showed differential behavior depend-ng on the cue and successfully learned the association of each cue with thection. The result suggests that this paradigm is useful for the electrophysio-ogical evaluation of DRN function in regulating response inhibition. We willecord single-unit activity in the DRN of monkeys performing the Go/No-goaccade task in future studies.esearch fund: PRESTO, HFSP, KAKENHI (20020028), KAKENHI (20300139).

oi:10.1016/j.neures.2011.07.1637

4-m20 VTA and NAcc neurons inhibition during reversalearning: A pharmacological and an optogenetic approachuca Aquili , Jeffrey Wickens

Okinawa Institute of Science and Technology

urpose: The aim of this study was to understand the contribution of VTA andacc cells in reversal learning performance by using two approaches. First,

nhibition of VTA and Nacc cells using a Gaba-a agonist (Muscimol). Second,nhibition of VTA and Nacc cells using light-sensitive opsins (halorhodopsin).he prediction from this investigation was that neuronal suppression of Nacceurons would have a greater impact on reversal learning performance thanuppression of VTA cells, as task complexity increased.ethods: Rats (Muscimol group) (n = 15) were implanted with bilateral guide

annulae above the VTA and Nacc. Another group of rats (n = 15) receivednjections of lentivirus (halorhodopsin) in the VTA and Nacc, and weremplanted with a fiber guide system that would deliver a yellow light to tar-et neurons via an optical fiber. After surgery, rats were trained to completen FR1 discrimination, and then tested in a between reversal and a withinession reversal task.esults: VTA (n = 5) and Nacc (n = 5) implanted rats that received muscimol

njections made significantly fewer errors during the between reversal ses-ion than the control group (saline, n = 5): F(1,14) = 42.885, p < 0.001. VTAats also took significantly longer than the control group to reach criterion:(1,14) = 4.933, p < 0.05. However, Nacc rats made significantly more errors

han the control group during the more complex within session reversal(1,14) = 7.031, p < 0.05.onclusion: Our preliminary results suggest that NAcc neurons play an

nstrumental role in reversal learning performance, especially when task

h 71S (2011) e108–e415 e373

complexity increases. The high temporal resolution provided by the opti-cal inhibition of NAcc and VTA neurons (via halorhodopsin) will provide uswith answers about the importance of feedback information when an erroris made.Research fund: OIST.

doi:10.1016/j.neures.2011.07.1638

P4-v13 Reversal learning and generalization in the com-mon marmosets (Callithrix jacchus)Yumiko Yamazaki 1,2 , Masakado Saiki 2, Masayuki Inada 2,Shigeru Watanabe 1,3, Atsushi Iriki 2

1 Grad. Sch. of Human Relations, Keio Univ., Tokyo, Japan 2 Lab. for Symbol.Cogn. Devel., RIKEN BSI, Saitama, Japan 3 Faculty of Letters, Keio Univ

Reversal learning has been widely used to assess the reward sensitivity inboth human and nonhuman animals. In this task the subjects have to attendto the relevant stimulus dimension (e.g., size, color, and shape of the stimuli)for reward, so it is also used to evaluate the categorical ability of the subjects.Reward sensitivity and categorical ability are highly important for adaptivebehavior, which is known to require intact brain function in orbitofrontal cor-tex. To establish the marmoset model of the cognitive abilities, we trained thecommon marmosets to perform simple discrimination using visual stimuli onthe touch monitor screen and evaluated their learning of repeated reversalsof the reward contingency. After habituated to the apparatus, the subjectswere required to select one out of two visual stimuli which differed in termsof the size. The subjects were trained to select, for example, the smaller stim-ulus of the two until their performance met the learning criterion. Once theymet the criterion, the reward contingency of the stimulus was reversed inthe next session (i.e. now the larger stimulus leads to the reinforcement).After several contingency reversals, they showed quick recovery of the per-formance in the first session of the reversal. Then, using the novel stimulussets, we tested their generalization performance whether they based theirresponses on the absolute or the relative stimulus size (i.e. transposition).Performance in the test trials suggested that they learned not only specificstimulus characteristics leading to the reinforcement, but the relative size ofthe stimulus combinations which was applicable to the novel situations.Research fund: The study was supported by the Centre for Advanced Researchon Logic and Sensibility, The Global COE Program, at Keio University, Japan,and the Funding Program for World-leading Innovative R&D on Science andTechnology, at RIKEN, Japan.

doi:10.1016/j.neures.2011.07.1639

P4-m21 BMAL1 plays a role in circadian regulation of mem-ory retrievalShunsuke Hasegawa 1,2 , Miho Ohta 1, Kaori Saito 1, AzumiNakamura 1, Hiroshi Hosoda 1, Satoshi Kida 1,2

1 Dept. of Biosci., Tokyo Univ. of Agri., Tokyo, Japan 2 CREST, JST

bHLH-PAS transcription factor BMAL1 has been shown to play essential rolesin circadian rhythm. BMAL1 functions by forming a heterodimer with eitherCLOCK or NPAS2 and regulates circadian transcriptional rhythms. Impor-tantly, previous studies have shown that BMAL1 ubiquitously expresses inthe brain and other peripheral tissues, thereby regulating circadian transcrip-tion rhythms in not only the SCN but also other cells including neurons inthe forebrain. In this study, we have tried to understand roles of BMAL1 inthe forebrain in learning and memory. To do this, we have derived condi-tional mutant mice that enable to induce the inhibition of BMAL1 functionin the forebrain by regulating expression of a dominant negative mutant ofBMAL1 (BMAL1 R91A; dnBMAL1) that forms a heterodimer with CLOCK butloses the binding activity with E-box (Hosoda et al., 2004). Biochemical anal-yses showed that dnBMAL1 mice exhibit disruptions of circadian expressioncycle of BAML1-target genes in the forebrain, but not in the hypothala-mus. In addition, dnBMAL1 mice displayed normal circadian rhythms atthe behavioral level. These results indicated that inhibition of BMAL1 activ-ity forebrain-specifically impairs circadian transcription rhythms withoutaffecting behavioral circadian rhythms. Behavioral analyses using socialrecognition, novel object recognition and contextual fear conditioning tasksshowed that these mutant mice displayed normal memory retrieval testedat ZT4, 16, or 22. In contrast, interestingly, these mutant mice exhibitedimpairments of memory retrieval tested at ZT10 in a dnBMAL1 expression-dependent manner. These findings indicate that CLOCK/BMAL1 signalingpathway in the forebrain contributes to circadian regulation of memory

retrieval.

doi:10.1016/j.neures.2011.07.1640