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Mol Brain. 2015 Jun 24;8:38. doi: 10.1186/s13041-015-0130-1.

Involvement of cAMP-guanine nucleotide exchange factor II in hippocampal long-term depression and behavioral flexibility.

Author information

1
Behavioral Neural Circuitry and Physiology Laboratory, Department of Anatomy, Brain Science & Engineering Institute, Kyungpook National University Graduate School of Medicine, 2-101, Dongin-dong, Jung-gu, Daegu, 700-842, Korea. irislkm@knu.ac.kr.
2
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, 2-1, Hirosawa, Wako-shi, Saitama, 351-0198, Japan. snow-k@brain.riken.jp.
3
Behavioral Neural Circuitry and Physiology Laboratory, Department of Anatomy, Brain Science & Engineering Institute, Kyungpook National University Graduate School of Medicine, 2-101, Dongin-dong, Jung-gu, Daegu, 700-842, Korea. hseo@knu.ac.kr.
4
Behavioral Neural Circuitry and Physiology Laboratory, Department of Anatomy, Brain Science & Engineering Institute, Kyungpook National University Graduate School of Medicine, 2-101, Dongin-dong, Jung-gu, Daegu, 700-842, Korea. kwakd7415@naver.com.
5
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, 2-1, Hirosawa, Wako-shi, Saitama, 351-0198, Japan. masuda-akira@brain.riken.jp.
6
Department of Biological Sciences, College of Natural Sciences, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul, 151-747, Korea. cslim@snu.ac.kr.
7
Department of Biological Sciences, College of Natural Sciences, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul, 151-747, Korea. hrlee15@snu.ac.kr.
8
Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, 151-746, Korea. sjkang24@snu.ac.kr.
9
Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, 151-746, Korea. pojeong@snu.ac.kr.
10
Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, 151-746, Korea. sesim@snu.ac.kr.
11
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, 2-1, Hirosawa, Wako-shi, Saitama, 351-0198, Japan. naomi_kogo@brain.riken.jp.
12
Department of Psychiatry, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan. hkawasaki@fukuoka-u.ac.jp.
13
Department of Biological Sciences, College of Natural Sciences, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul, 151-747, Korea. kaang@snu.ac.kr.
14
Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, 151-746, Korea. kaang@snu.ac.kr.
15
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, 2-1, Hirosawa, Wako-shi, Saitama, 351-0198, Japan. sitohara@brain.riken.jp.

Abstract

BACKGROUND:

Guanine nucleotide exchange factors (GEFs) activate small GTPases that are involved in several cellular functions. cAMP-guanine nucleotide exchange factor II (cAMP-GEF II) acts as a target for cAMP independently of protein kinase A (PKA) and functions as a GEF for Rap1 and Rap2. Although cAMP-GEF II is expressed abundantly in several brain areas including the cortex, striatum, and hippocampus, its specific function and possible role in hippocampal synaptic plasticity and cognitive processes remain elusive. Here, we investigated how cAMP-GEF II affects synaptic function and animal behavior using cAMP-GEF II knockout mice.

RESULTS:

We found that deletion of cAMP-GEF II induced moderate decrease in long-term potentiation, although this decrease was not statistically significant. On the other hand, it produced a significant and clear impairment in NMDA receptor-dependent long-term depression at the Schaffer collateral-CA1 synapses of hippocampus, while microscopic morphology, basal synaptic transmission, and depotentiation were normal. Behavioral testing using the Morris water maze and automated IntelliCage system showed that cAMP-GEF II deficient mice had moderately reduced behavioral flexibility in spatial learning and memory.

CONCLUSIONS:

We concluded that cAMP-GEF II plays a key role in hippocampal functions including behavioral flexibility in reversal learning and in mechanisms underlying induction of long-term depression.

PMID:
26104314
PMCID:
PMC4477293
DOI:
10.1186/s13041-015-0130-1
[Indexed for MEDLINE]
Free PMC Article

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