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Comprehensive behavioral characterization of mice lacking ICER, an endogenous antagonist of CREB
Abstracts / Neuroscience Research 58S (2007) S1–S244
S225
P3-g26 Distinctive neuronal networks and biochemical path-
P3-g29 Effect of perirhinal cortex lesion on relearning of recog-
ways in appetitive and aversive memory in Drosophila larvae
nition memory tasks with large and small sets of stimuli in monkey
Ken Honjo, Asami Tanaka, Katsuo Furukubo-Tokunaga Grad. Schl. Life & Envir. Sci., Univ. Tsukuba, Japan
Masao Yukie 1,2 , Yasutata Osawa 2 Department of Child Psychology, Tokyo Future University, Tokyo, Japan; 2 Tokyo Metropolitan Institute for Neuroscience, Fuchu, Japan
1
In classical conditioning, animals learn association of originally neutral stimuli (conditioned stimuli, CS) with unconditioned stimuli (US), which elicit reflexive responses. Whereas associative strength between CS and US is thought to determine learning efficacy, little is know on the neuronal processes that underlie differential CS-US association in the brain. In Drosophila larvae, appetitive but not aversive training induces medium-term memory, which is dependent on amn and CREB, whereas both conditionings produce short-term memory depending on cAMP signaling. Neurocircuitry analyses suggest that, in either training, memory is stored in mushroom bodies and/or antennal lobes despite that neural output of octopaminergic and dopaminergic pathways, which exhibit distinct innervation patterns, are required for appetitive and aversive memory formation, respectively. These results suggest that genetically programmed US pathways involved in memory acquisition may determine different memory spans activating additional cAMP-dependent molecular components in the brain.
Behavioral studies in monkeys have demonstrated that relearning of recognition memory with a large set of stimuli is impaired by perirhinal cortex (PRC) lesion. However, it has not been known whether experience of recognition memory with a small set of stimuli prior the PRC damage gives impairments in relearning of it with large and small sets of stimuli after the lesion or not. We examined this issue using 4 Japanese monkeys (Macaca fuscata) and 2 rhesus monkeys (Macaca mulatto) in WGTA. Prior PRC lesion, each monkey was trained on delayed matching to sample with two sets of stimuli, first with a large set of stimuli (300 pictured stimuli: DMS-300) and next with a small set of ones (3 pictured stimuli: DMS-3). After PRC ablations in 3monkeys, all monkeys were re-trained first on DMS-3 and next on DMS-300. After relearning of each DMS task, delay test (30, 60 and 120 s delays) was given. As a result, no impairment was shown on relearning of the 2 DMS tasks and on delay tests. Research fund: KAKENHI (14510115).
P3-g27 Involvement of a Drosophila transient receptor potential ion channel gene painless in long-term courtship memory Takaomi Sakai 1 , Toshiro Aigaki 1 , Toshihiro Kitamoto 2 Department of Biological Sciences, Tokyo Metropolitan University, Tokyo, Japan; 2 Department of Anesthesia, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
P3-g3Ø Overexpression of ICER, an endogenous antagonist of CREB, impairs fear memory M. Arai 1 , G. Borlikova 1 , N. Kojima 2 , S. Endo 1 Okinawa Institute of Science and Technology, Okinawa, Japan; 2 Department of Neurobiology and Behavior, Gunma University, Graduate School of Medicine, Maebashi, Japan
1
1
The transient receptor potential (TRP) channels play various roles in sensory transduction, but little is known about their physiological function in the brain. The Drosophila painless gene (pain) encodes a TRP channel of the TRPA subfamily. Interestingly, strong pain expression is observed in the adult mushroom bodies (MBs) that are involved in various learning and memory paradigms. Hence, we tested pain mutants for associative memory using the courtship-conditioning assay, where experience with mated females causes males to reduce their courtship toward virgins. Pain mutants were defective in long-term courtship memory, which are rescued by wild type pain preferentially expressed in the mushroom body neurons. Furthermore, Flies expressing pain RNAi in the MBs showed the defective long-term courtship memory. Our results indicate involvement of the brain TRP channel in the behavioral plasticity.
Inducible cAMP early repressor (ICER) is an endogenous antagonist of CRE binding protein (CREB). Negative feedback regulation of CREB activity by ICER might play an important role in memory formation process. Three lines of transgenic mice showing overexpression (O/E) of ICER constitutively in forebrain were examined. ICER-I line 23 mice (∼125-fold O/E) showed impaired context fear memory tested 24 hr after conditioning, despite unaltered short-term context memory and tone-induced fear memory. These mice also showed unchanged general behavioral profiles. ICER-I line 15 mice (∼80-fold O/E) did not exhibit any major changes in behavioral profiles examined. In contrast, mice overexpressing ICER-II, another isoform of ICER (∼585-fold O/E), showed not only impaired long-term fear memory, but also altered phenotypes in a number of other behavioral tests. The results show importance of the negative regulation exerted by ICER for long-term fear memory, the effect that seems to depend on the O/E level of transgene.
P3-g28 Comprehensive behavioral characterization of mice lacking ICER, an endogenous antagonist of CREB
P3-g31 Dependency on the ipsilateral cerebellum in rat eyeblink conditioning
G. Borlikova 1 , M. Arai 1 , N. Kojima 2 , S. Endo 1 1 Okinawa Institute of Science and Technology, Okinawa, Japan; 2 Department of Neurobiology and Behavior, Gunma University, Graduate School of Medicine, Maebashi, Japan
Takahiro Horiuchi 1,2 , Shigenori Kawahara 2 1 Laboratory of Neurobiophysics, The University of Tokyo, Japan; 2 Dpt. Material Systems Engineering and Life Sci., Fac. Engineering, Toyama University, Japan
Inducible cAMP early repressor (ICER) is an inducible repressor of CREmediated gene transcription. ICER knockout (KO) mice were assessed using test battery. KO mice had similar body weight and home cage activity to wild-type littermates. While demonstrating unchanged behavior in the open field and elevated plus maze under dim conditions, KO mice showed lower locomotor activity in the brightly lit open field and in the light/dark test, taking longer time to enter the light compartment. KO mice performed better than wild-type littermates in the water maze task: shorter escape latency and path length, less time spent near the wall and better performance in the probe test. At the same time, KO mice did not differ from controls in tests on motor performance. Finally, KO mice showed tendency to freeze more during contextual fear test 24 h after conditioning. The results may suggest roles of ICER in regulation of emotional state in anxiogenic situations and certain types of learning.
The ipsilateral cerebellum to the trained eye has been reported to be essential for classical conditioning of eyeblink responses in rabbits. However, recent reports suggest that the ipsilateral cerebellum might not be essential in mice and humans. In this work, we examined roles of the ipsilateral and contralateral cerebellum in rats. They were conditioned for 7 days with a 150-, 250- or 500-ms interstimulus interval (ISI) in delay paradigm using a tone and a periorbital electrical shock. Then, they received aspiration of the ipsilateral or contralateral cerebellum. After more than three weeks, they were conditioned again for 10 days. Irrespective of the ISI, the ipsilateral group showed a severe impairment in retaining their conditioned response (CR). However, many of them reacquired precisely timed CRs during the re-conditioning. Contralateral cerebellar ablation in 500-ms ISI caused a similar but less impairment. These results suggest an involvement of the ipsilateral cerebellum in rats, which, however, can learn without it.
S225
P3-g26 Distinctive neuronal networks and biochemical path-
P3-g29 Effect of perirhinal cortex lesion on relearning of recog-
ways in appetitive and aversive memory in Drosophila larvae
nition memory tasks with large and small sets of stimuli in monkey
Ken Honjo, Asami Tanaka, Katsuo Furukubo-Tokunaga Grad. Schl. Life & Envir. Sci., Univ. Tsukuba, Japan
Masao Yukie 1,2 , Yasutata Osawa 2 Department of Child Psychology, Tokyo Future University, Tokyo, Japan; 2 Tokyo Metropolitan Institute for Neuroscience, Fuchu, Japan
1
In classical conditioning, animals learn association of originally neutral stimuli (conditioned stimuli, CS) with unconditioned stimuli (US), which elicit reflexive responses. Whereas associative strength between CS and US is thought to determine learning efficacy, little is know on the neuronal processes that underlie differential CS-US association in the brain. In Drosophila larvae, appetitive but not aversive training induces medium-term memory, which is dependent on amn and CREB, whereas both conditionings produce short-term memory depending on cAMP signaling. Neurocircuitry analyses suggest that, in either training, memory is stored in mushroom bodies and/or antennal lobes despite that neural output of octopaminergic and dopaminergic pathways, which exhibit distinct innervation patterns, are required for appetitive and aversive memory formation, respectively. These results suggest that genetically programmed US pathways involved in memory acquisition may determine different memory spans activating additional cAMP-dependent molecular components in the brain.
Behavioral studies in monkeys have demonstrated that relearning of recognition memory with a large set of stimuli is impaired by perirhinal cortex (PRC) lesion. However, it has not been known whether experience of recognition memory with a small set of stimuli prior the PRC damage gives impairments in relearning of it with large and small sets of stimuli after the lesion or not. We examined this issue using 4 Japanese monkeys (Macaca fuscata) and 2 rhesus monkeys (Macaca mulatto) in WGTA. Prior PRC lesion, each monkey was trained on delayed matching to sample with two sets of stimuli, first with a large set of stimuli (300 pictured stimuli: DMS-300) and next with a small set of ones (3 pictured stimuli: DMS-3). After PRC ablations in 3monkeys, all monkeys were re-trained first on DMS-3 and next on DMS-300. After relearning of each DMS task, delay test (30, 60 and 120 s delays) was given. As a result, no impairment was shown on relearning of the 2 DMS tasks and on delay tests. Research fund: KAKENHI (14510115).
P3-g27 Involvement of a Drosophila transient receptor potential ion channel gene painless in long-term courtship memory Takaomi Sakai 1 , Toshiro Aigaki 1 , Toshihiro Kitamoto 2 Department of Biological Sciences, Tokyo Metropolitan University, Tokyo, Japan; 2 Department of Anesthesia, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
P3-g3Ø Overexpression of ICER, an endogenous antagonist of CREB, impairs fear memory M. Arai 1 , G. Borlikova 1 , N. Kojima 2 , S. Endo 1 Okinawa Institute of Science and Technology, Okinawa, Japan; 2 Department of Neurobiology and Behavior, Gunma University, Graduate School of Medicine, Maebashi, Japan
1
1
The transient receptor potential (TRP) channels play various roles in sensory transduction, but little is known about their physiological function in the brain. The Drosophila painless gene (pain) encodes a TRP channel of the TRPA subfamily. Interestingly, strong pain expression is observed in the adult mushroom bodies (MBs) that are involved in various learning and memory paradigms. Hence, we tested pain mutants for associative memory using the courtship-conditioning assay, where experience with mated females causes males to reduce their courtship toward virgins. Pain mutants were defective in long-term courtship memory, which are rescued by wild type pain preferentially expressed in the mushroom body neurons. Furthermore, Flies expressing pain RNAi in the MBs showed the defective long-term courtship memory. Our results indicate involvement of the brain TRP channel in the behavioral plasticity.
Inducible cAMP early repressor (ICER) is an endogenous antagonist of CRE binding protein (CREB). Negative feedback regulation of CREB activity by ICER might play an important role in memory formation process. Three lines of transgenic mice showing overexpression (O/E) of ICER constitutively in forebrain were examined. ICER-I line 23 mice (∼125-fold O/E) showed impaired context fear memory tested 24 hr after conditioning, despite unaltered short-term context memory and tone-induced fear memory. These mice also showed unchanged general behavioral profiles. ICER-I line 15 mice (∼80-fold O/E) did not exhibit any major changes in behavioral profiles examined. In contrast, mice overexpressing ICER-II, another isoform of ICER (∼585-fold O/E), showed not only impaired long-term fear memory, but also altered phenotypes in a number of other behavioral tests. The results show importance of the negative regulation exerted by ICER for long-term fear memory, the effect that seems to depend on the O/E level of transgene.
P3-g28 Comprehensive behavioral characterization of mice lacking ICER, an endogenous antagonist of CREB
P3-g31 Dependency on the ipsilateral cerebellum in rat eyeblink conditioning
G. Borlikova 1 , M. Arai 1 , N. Kojima 2 , S. Endo 1 1 Okinawa Institute of Science and Technology, Okinawa, Japan; 2 Department of Neurobiology and Behavior, Gunma University, Graduate School of Medicine, Maebashi, Japan
Takahiro Horiuchi 1,2 , Shigenori Kawahara 2 1 Laboratory of Neurobiophysics, The University of Tokyo, Japan; 2 Dpt. Material Systems Engineering and Life Sci., Fac. Engineering, Toyama University, Japan
Inducible cAMP early repressor (ICER) is an inducible repressor of CREmediated gene transcription. ICER knockout (KO) mice were assessed using test battery. KO mice had similar body weight and home cage activity to wild-type littermates. While demonstrating unchanged behavior in the open field and elevated plus maze under dim conditions, KO mice showed lower locomotor activity in the brightly lit open field and in the light/dark test, taking longer time to enter the light compartment. KO mice performed better than wild-type littermates in the water maze task: shorter escape latency and path length, less time spent near the wall and better performance in the probe test. At the same time, KO mice did not differ from controls in tests on motor performance. Finally, KO mice showed tendency to freeze more during contextual fear test 24 h after conditioning. The results may suggest roles of ICER in regulation of emotional state in anxiogenic situations and certain types of learning.
The ipsilateral cerebellum to the trained eye has been reported to be essential for classical conditioning of eyeblink responses in rabbits. However, recent reports suggest that the ipsilateral cerebellum might not be essential in mice and humans. In this work, we examined roles of the ipsilateral and contralateral cerebellum in rats. They were conditioned for 7 days with a 150-, 250- or 500-ms interstimulus interval (ISI) in delay paradigm using a tone and a periorbital electrical shock. Then, they received aspiration of the ipsilateral or contralateral cerebellum. After more than three weeks, they were conditioned again for 10 days. Irrespective of the ISI, the ipsilateral group showed a severe impairment in retaining their conditioned response (CR). However, many of them reacquired precisely timed CRs during the re-conditioning. Contralateral cerebellar ablation in 500-ms ISI caused a similar but less impairment. These results suggest an involvement of the ipsilateral cerebellum in rats, which, however, can learn without it.