Social Isolation Selectively Increases Anxiety in Mice without Affecting Depression-like Behavior

Chuljung Kwak,Sue-Hyun Lee,Bong-Kiun Kaang 대한생리학회-대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.5

It is hypothesized that a number of environmental factors affect animals behavior. Without controlling these variables, it is very hard for researchers to get not only reliable, but replicable data from various behavioral experiments testing animals cognitive as well as emotional functions. For example, laboratory mice which had restricted environment showed different synaptic potentiation properties with wild mice (Zhao MG et al., 2009). While performing behavioral experiments, however, it is sometimes inevitable that the researcher changes the animals environments, as by switching the cages in which experimental animals are housed and separating animals raised together into small experimental groups. In this study, we investigated the effect of environmental changes on mice s emotional behaviors by socially isolating them or reducing the size of their cage. We found that social isolation selectively increases the animals levels of anxiety, while leaving depression-like behaviors unchanged. On the other hand, alteration of the housing dimensions affected neither their anxiety levels nor their depression-like behaviors. These results suggest that environmental variables may have a prominent impact on experimental animals emotional behaviors and possibly their psychological states, leading to bias in the behavioral data produced from experiments.

Effect of Intensity of Unconditional Stimulus on Reconsolidation of Contextual Fear Memory

Chuljung Kwak,Jun-Hyeok Choi,Joseph T. Bakes,Kyungmin Lee,Bong-Kiun Kaang 대한생리학회-대한약리학회 2012 The Korean Journal of Physiology & Pharmacology Vol.15 No.5

Memory reconsolidation is ubiquitous across species and various memory tasks. It is a dynamic process in which memory is modified and/or updated. In experimental conditions, memory reconsolidation is usually characterized by the fact that the consolidated memory is disrupted by a combination of memory reactivation and inhibition of protein synthesis. However, under some experimental conditions, the reactivated memory is not disrupted by inhibition of protein synthesis. This so called boundary condition of reconsolidation may be related to memory strength. In Pavlovian fear conditioning, the intensity of unconditional stimulus (US) determines the strength of the fear memory. In this study, we examined the effect of the intensity of US on the reconsolidation of contextual fear memory. Strong contextual fear memory, which is conditioned with strong US, is not disrupted by inhibition of protein synthesis after its reactivation; however, a weak fear memory is often disrupted. This suggests that a US of strong intensity can inhibit reconsolidation of contextual fear memory.

Effect of Intensity of Unconditional Stimulus on Reconsolidation of Contextual Fear Memory

Chuljung Kwak,Jun-Hyeok Choi,Joseph T. Bakes,이경민,강봉균 대한약리학회 2012 The Korean Journal of Physiology & Pharmacology Vol.16 No.5

Memory reconsolidation is ubiquitous across species and various memory tasks. It is a dynamic process in which memory is modified and/or updated. In experimental conditions, memory reconsolidation is usually characterized by the fact that the consolidated memory is disrupted by a combination of memory reactivation and inhibition of protein synthesis. However, under some experimental conditions, the reactivated memory is not disrupted by inhibition of protein synthesis. This so called “boundary condition” of reconsolidation may be related to memory strength. In Pavlovian fear conditioning, the intensity of unconditional stimulus (US) determines the strength of the fear memory. In this study, we examined the effect of the intensity of US on the reconsolidation of contextual fear memory. Strong contextual fear memory, which is conditioned with strong US, is not disrupted by inhibition of protein synthesis after its reactivation; however, a weak fear memory is often disrupted. This suggests that a US of strong intensity can inhibit reconsolidation of contextual fear memory.

Development of a Touch-Screen-Based Paradigm for Assessing Working Memory in the Mouse

Kwak, Chuljung,Lim, Chae-Seok,Kaang, Bong-Kiun The Korean Society for Brain and Neural Science 2015 Experimental Neurobiology Vol.24 No.1

<P>Assessing the working memory of the rodent by using a touch-screen system has several advantages (e.g., allowing highly accurate data collection and flexibility in memory task design). However, there is currently no available testing paradigm utilizing touch-screen systems that can assess working memory in the mouse. In this study, we developed a touch-screen testing paradigm in which mice were trained to choose a location that is matched to a sample location after a time delay. Consistent with previous studies, this study showed that mice could not only learn the rule in the delayed matched to position (DMTP), but also could retain a transitory memory of the sample position during delay. This indicates that a touch-screen system can provide a DMTP testing platform to assess working memory in the mouse.</P>

β-Adrenergic signaling is required for the induction of a labile state during memory reconsolidation

Lim, Chae-Seok,Kim, Jae-Ick,Kwak, Chuljung,Lee, Jaehyun,Jang, Eun Hae,Oh, Jihae,Kaang, Bong-Kiun Elsevier 2018 Brain research bulletin Vol.141 No.-

<P><B>Abstract</B></P> <P>Memory reconsolidation is the process by which previously consolidated memories reenter a labile state through reactivation of the memory trace and are actively consolidated through <I>de novo</I> protein synthesis. Although extensive studies have shown that β-adrenergic signaling plays a critical role in the restabilization of reactivated memory, its role in the destabilization of long-term memory is not well-studied. In this study, we found that membrane excitability increased in hippocampal CA1 neurons immediately after the retrieval of contextual fear memory. Interestingly, this increase in membrane excitability diminished after treatment with propranolol (a β-adrenergic receptor antagonist), an NMDA receptor antagonist, and a PKA inhibitor. In addition, we found that administration of propranolol prior to, but not after, the retrieval of fear memory ameliorated the memory impairment caused by anisomycin, indicating that inhibition of β-adrenergic signaling blocks the destabilization of contextual fear memory. Taken together, these results indicate that β-adrenergic signaling via NMDA receptors and PKA signaling pathway induces a labile state of long-term memory through increased neuronal membrane excitability.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Retrieval of contextual fear memory increases the membrane excitability. </LI> <LI> Propranolol or NMDAR and PKA inhibition diminishes membrane hyperexcitability. </LI> <LI> β-adrenergic signaling is required for the destabilization of contextual fear memory. </LI> </UL> </P>

Inhibition of anterior cingulate cortex excitatory neuronal activity induces conditioned place preference in a mouse model of chronic inflammatory pain

Kang, Sukjae Joshua,Kim, Siyong,Lee, Jaehyun,Kwak, Chuljung,Lee, Kyungmin,Zhuo, Min,Kaang, Bong-Kiun The Korean Society of Pharmacology 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.5

The anterior cingulate cortex (ACC) is known for its role in perception of nociceptive signals and the associated emotional responses. Recent optogenetic studies, involving modulation of neuronal activity in the ACC, show that the ACC can modulate mechanical hyperalgesia. In the present study, we used optogenetic techniques to selectively modulate excitatory pyramidal neurons and inhibitory interneurons in the ACC in a model of chronic inflammatory pain to assess their motivational effect in the conditioned place preference (CPP) test. Selective inhibition of pyramidal neurons induced preference during the CPP test, while activation of parvalbumin (PV)-specific neurons did not. Moreover, chemogenetic inhibition of the excitatory pyramidal neurons alleviated mechanical hyperalgesia, consistent with our previous result. Our results provide evidence for the analgesic effect of inhibition of ACC excitatory pyramidal neurons and a prospective treatment for chronic pain.

Multiple repressive mechanisms in the hippocampus during memory formation

Cho, Jun,Yu, Nam-Kyung,Choi, Jun-Hyeok,Sim, Su-Eon,Kang, SukJae Joshua,Kwak, Chuljung,Lee, Seung-Woo,Kim, Ji-il,Choi, Dong Il,Kim, V. Narry,Kaang, Bong-Kiun American Association for the Advancement of Scienc 2015 Science Vol.350 No.6256

<P><B>Memory consolidation by gene suppression</B></P><P>Storing a persistent memory in the brain involves dynamic gene regulation. However, our knowledge of the target genes controlled during memory formation is limited. Cho <I>et al.</I> used RNA sequencing and ribosome profiling to compare transcription and translational levels in the mouse hippocampus before and after memory formation. Under basal conditions, there was an unexpected translational repression of ribosomal protein-coding genes. Early after learning, specific genes were translationally repressed. Later, suppression of a group of genes resulted from the inhibition of estrogen receptor alpha signaling. Thus, suppression mechanisms in the hippocampus appear to play a major role during memory consolidation.</P><P><I>Science</I>, this issue p. 82</P><P>Memory stabilization after learning requires translational and transcriptional regulations in the brain, yet the temporal molecular changes that occur after learning have not been explored at the genomic scale. We used ribosome profiling and RNA sequencing to quantify the translational status and transcript levels in the mouse hippocampus after contextual fear conditioning. We revealed three types of repressive regulations: translational suppression of ribosomal protein-coding genes in the hippocampus, learning-induced early translational repression of specific genes, and late persistent suppression of a subset of genes via inhibition of estrogen receptor 1 (ESR1/ERα) signaling. In behavioral analyses, overexpressing <I>Nrsn1</I>, one of the newly identified genes undergoing rapid translational repression, or activating ESR1 in the hippocampus impaired memory formation. Collectively, this study unveils the yet-unappreciated importance of gene repression mechanisms for memory formation.</P>

PI3K款 is required for NMDA receptor??dependent long-term depression and behavioral flexibility

Kim, Jae-Ick,Lee, Hye-Ryeon,Sim, Su-eon,Baek, Jinhee,Yu, Nam-Kyung,Choi, Jun-Hyeok,Ko, Hyoung-Gon,Lee, Yong-Seok,Park, Soo-Won,Kwak, Chuljung,Ahn, Sung-Ji,Choi, So Yoen,Kim, Hyun,Kim, Kyoung-Han,Backx Nature Publishing Group, a division of Macmillan P 2011 NATURE NEUROSCIENCE Vol.14 No.11

<P>Phosphatidylinositol 3-kinase (PI3K) has been implicated in synaptic plasticity and other neural functions in the brain. However, the role of individual PI3K isoforms in the brain is unclear. We investigated the role of PI3K gamma in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3K gamma has a crucial and specific role in NMDA receptor (NMDAR)-mediated synaptic plasticity at mouse Schaffer collateral-commissural synapses. Both genetic deletion and pharmacological inhibition of PI3K gamma disrupted NMDAR long-term depression (LTD) while leaving other forms of synaptic plasticity intact. Accompanying this physiological deficit, the impairment of NMDAR LTD by PI3K gamma blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3K gamma, is critical for NMDAR LTD and some forms of cognitive function. Thus, individual isoforms of PI3Ks may have distinct roles in different types of synaptic plasticity and may therefore influence various kinds of behavior.</P>