Acute immobilization stress following contextual fear conditioning reduces fear memory: timing is essential

Following learning, increased coupling between spindle oscillations in the medial prefrontal cortex (mPFC) and ripple oscillations in the hippocampus is thought to underlie memory consolidation. However, whether learning-induced increases in ripple-spindle coupling are necessary for successful memory consolidation has not been tested directly. In order to decouple ripple-spindle oscillations, here we chemogenetically inhibited parvalbumin-positive (PV+) interneurons, since their activity is important for regulating the timing of spiking activity during oscillations. We found that contextual fear conditioning increased ripple-spindle coupling in mice. However, inhibition of PV+ cells in either CA1 or mPFC eliminated this learning-induced increase in ripple-spindle coupling without affecting ripple or spindle incidence. Consistent with the hypothesized importance of ripple-spindle coupling in memory consolidation, post-training inhibition of PV+ cells disrupted contextual fear memory consolidation. These results indicate that successful memory consolidation requires coherent hippocampal-neocortical communication mediated by PV+ cells.

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Corticosterone Treatment and Incubation Time After Contextual Fear Conditioning Synergistically Induce Fear Memory Generalization in Neuropeptide S Receptor-Deficient Mice

Frontiers in Neuroscience ◽

10.3389/fnins.2020.00128 ◽

2020 ◽

Vol 14 ◽

Author(s):

Malgorzata H. Kolodziejczyk ◽

Markus Fendt

Keyword(s):

Fear Conditioning ◽

Incubation Time ◽

Fear Memory ◽

Contextual Fear Conditioning ◽

Neuropeptide S ◽

Contextual Fear ◽

Corticosterone Treatment ◽

Deficient Mice

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Contextual Fear Memory Maintenance Changes Expression of pMAPK, BDNF and IBA-1 in the Pre-limbic Cortex in a Layer-Specific Manner

Frontiers in Neural Circuits ◽

10.3389/fncir.2021.660199 ◽

2021 ◽

Vol 15 ◽

Author(s):

Nicholas Chaaya ◽

Joshua Wang ◽

Angela Jacques ◽

Kate Beecher ◽

Michael Chaaya ◽

...

Keyword(s):

Fear Conditioning ◽

Fear Memory ◽

Contextual Fear Conditioning ◽

Mitogen Activated Protein Kinase ◽

Limbic Cortex ◽

Pavlovian Fear Conditioning ◽

Bdnf Expression ◽

Contextual Fear ◽

Contextual Fear Memory

Post-traumatic stress disorder (PTSD) is a debilitating and chronic fear-based disorder. Pavlovian fear conditioning protocols have long been utilised to manipulate and study these fear-based disorders. Contextual fear conditioning (CFC) is a particular Pavlovian conditioning procedure that pairs fear with a particular context. Studies on the neural mechanisms underlying the development of contextual fear memories have identified the medial prefrontal cortex (mPFC), or more specifically, the pre-limbic cortex (PL) of the mPFC as essential for the expression of contextual fear. Despite this, little research has explored the role of the PL in contextual fear memory maintenance or examined the role of neuronal mitogen-activated protein kinase (pMAPK; ERK 1/2), brain-derived neurotrophic factor (BDNF), and IBA-1 in microglia in the PL as a function of Pavlovian fear conditioning. The current study was designed to evaluate how the maintenance of two different long-term contextual fear memories leads to changes in the number of immune-positive cells for two well-known markers of neural activity (phosphorylation of MAPK and BDNF) and microglia (IBA-1). Therefore, the current experiment is designed to assess the number of immune-positive pMAPK and BDNF cells, microglial number, and morphology in the PL following CFC. Specifically, 2 weeks following conditioning, pMAPK, BDNF, and microglia number and morphology were evaluated using well-validated antibodies and immunohistochemistry (n = 12 rats per group). A standard CFC protocol applied to rats led to increases in pMAPK, BDNF expression and microglia number as compared to control conditions. Rats in the unpaired fear conditioning (UFC) procedure, despite having equivalent levels of fear to context, did not have any change in pMAPK, BDNF expression and microglia number in the PL compared to the control conditions. These data suggest that alterations in the expression of pMAPK, BDNF, and microglia in the PL can occur for up to 2 weeks following CFC. Together the data suggest that MAPK, BDNF, and microglia within the PL of the mPFC may play a role in contextual fear memory maintenance.

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Cerebellar molecular layer interneurons are dispensable for cued and contextual fear conditioning

Scientific Reports ◽

10.1038/s41598-020-76729-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Katy L. H. Marshall-Phelps ◽

Gernot Riedel ◽

Peer Wulff ◽

Marta Woloszynowska-Fraser

Keyword(s):

Fear Conditioning ◽

Purkinje Cells ◽

Cerebellar Cortex ◽

Conditioned Fear ◽

Molecular Layer ◽

Fear Memory ◽

Memory Formation ◽

Contextual Fear Conditioning ◽

Contextual Fear

AbstractPurkinje cells are the only output cell of the cerebellar cortex. Their spatiotemporal activity is controlled by molecular layer interneurons (MLIs) through GABAA receptor-mediated inhibition. Recently, it has been reported that the cerebellar cortex is required for consolidation of conditioned fear responses during fear memory formation. Although the relevance of MLIs during fear memory formation is currently not known, it has been shown that synapses made between MLIs and Purkinje cells exhibit long term plasticity following fear conditioning. The present study examined the role of cerebellar MLIs in the formation of fear memory using a genetically-altered mouse line (PC-∆γ2) in which GABAA receptor-mediated signaling at MLI to Purkinje cell synapses was functionally removed. We found that neither acquisition nor recall of fear memories to tone and context were altered after removal of MLI-mediated inhibition.

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Short-Term Total Sleep-Deprivation Impairs Contextual Fear Memory, and Contextual Fear-Conditioning Reduces REM Sleep in Moderately Anxious Swiss Mice

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2017.00239 ◽

2017 ◽

Vol 11 ◽

Cited By ~ 9

Author(s):

Munazah F. Qureshi ◽

Sushil K. Jha

Keyword(s):

Sleep Deprivation ◽

Fear Conditioning ◽

Rem Sleep ◽

Fear Memory ◽

Contextual Fear Conditioning ◽

Short Term ◽

Contextual Fear ◽

Total Sleep Deprivation ◽

Contextual Fear Memory ◽

Swiss Mice

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Ca2+/Calmodulin Kinase Kinase α Is Dispensable for Brain Development but Is Required for Distinct Memories in Male, though Not in Female, Mice

Molecular and Cellular Biology ◽

10.1128/mcb.01221-06 ◽

2006 ◽

Vol 26 (23) ◽

pp. 9094-9104 ◽

Cited By ~ 35

Author(s):

Keiko Mizuno ◽

Laurence Ris ◽

Amelia Sánchez-Capelo ◽

Emile Godaux ◽

K. Peter Giese

Keyword(s):

Brain Development ◽

Mrna Expression ◽

Fear Conditioning ◽

Fear Memory ◽

Memory Formation ◽

Contextual Fear Conditioning ◽

Cam Kinase ◽

Contextual Fear ◽

Contextual Fear Memory ◽

Kinase Cascade

ABSTRACT In neurons, the Ca2+/calmodulin (CaM) kinase cascade transduces Ca2+ signaling into gene transcription. The CaM kinase cascade is known to be important for brain development as well as memory formation in adult brain, although the functions of some cascade members remain unknown. Here we have generated null and hypomorphic mutants to study the physiological role of CaM kinase kinase α (CaMKKα), which phosphorylates and activates both CaM kinase I (CaMKI) and CaMKIV, the output kinases of the cascade. We show that CaMKKα is dispensable for brain development and long-term potentiation in adult hippocampal CA1 synapses. We find that CaMKKα is required for hippocampus-dependent contextual fear memory, but not spatial memory, formation. Surprisingly, CaMKKα is important for contextual fear memory formation in males but not in females. We show that in male mice, contextual fear conditioning induces up-regulation of hippocampal mRNA expression of brain-derived neurotrophic factor (BDNF) in a way that requires CaMKKα, while in female mice, contextual fear conditioning induces down-regulation of hippocampal BDNF mRNA expression that does not require CaMKKα. Additionally, we demonstrate sex-independent up-regulation in hippocampal nerve growth factor-inducible gene B mRNA expression that does not require CaMKKα. Thus, we show that CaMKKα has a specific complex role in memory formation in males.

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ErbB4 Receptors in the Medial Habenula Regulate Contextual Fear Memory

Pharmacology ◽

10.1159/000495064 ◽

2018 ◽

Vol 103 (1-2) ◽

pp. 68-75 ◽

Cited By ~ 1

Author(s):

Fei Geng ◽

Jia-Yun Liu ◽

Xiao-Wen Chen ◽

Wen-Jun Zou ◽

Jian-Lin Wu ◽

...

Keyword(s):

Fear Conditioning ◽

Fear Memory ◽

Contextual Fear Conditioning ◽

Mrna Levels ◽

Contextual Fear ◽

Electrophysiological Recordings ◽

Medial Habenula ◽

Erbb4 Receptor ◽

Polymerase Chain

The Medial Habenular (MHb) and the Lateral Habenular nuclei are 2 main parts of the habenular complex (Hb). Recent studies showed that MHb plays an important role in memory, and in the expression of ErbB4. However, the expression of MHb ErbB4 receptor and its role in fear memory is not well understood. In this study, western blotting and quantitative real-time polymerase chain reaction were used to assess the protein and mRNA levels of ErbB4 in the process of contextual fear conditioning. A pharmacological approach was used to block and stimulate the ErbB4 receptor. Contextual fear conditioning tests induced a significant increase on the expression of ErbB4 at various times in the Hb and the MHb. Moreover, the blockade and stimulation of MHb ErbB4 receptors did not affect the fear formation but impaired and improved the contextual-dependent fear expression. Furthermore, in vitro electrophysiological recordings showed that the blockade of the MHb ErbB4 receptor reduced the presynaptic gamma-amino butyric acid release. ErbB4 is a susceptible gene for schizophrenia and the above findings may provide new insights into the mechanisms of fear-related responses.

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