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

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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Parvalbumin-positive interneurons mediate neocortical-hippocampal interactions that are necessary for memory consolidation

eLife ◽

10.7554/elife.27868 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 56

Author(s):

Frances Xia ◽

Blake A Richards ◽

Matthew M Tran ◽

Sheena A Josselyn ◽

Kaori Takehara-Nishiuchi ◽

...

Keyword(s):

Prefrontal Cortex ◽

Fear Conditioning ◽

Medial Prefrontal Cortex ◽

Memory Consolidation ◽

Fear Memory ◽

Contextual Fear Conditioning ◽

Contextual Fear ◽

Contextual Fear Memory ◽

Spiking Activity

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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Molecular motor KIF3B in the prelimbic cortex constrains the consolidation of contextual fear memory

Molecular Brain ◽

10.1186/s13041-021-00873-9 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Nadine F. Joseph ◽

Aya Zucca ◽

Jenna L. Wingfield ◽

Isabel Espadas ◽

Damon Page ◽

...

Keyword(s):

Molecular Motor ◽

Fear Memory ◽

Contextual Fear Conditioning ◽

Prelimbic Cortex ◽

Spine Density ◽

Cellular Mechanisms ◽

Contextual Fear ◽

Contextual Fear Memory ◽

And Function

AbstractMolecular and cellular mechanisms underlying the role of the prelimbic cortex in contextual fear memory remain elusive. Here we examined the kinesin family of molecular motor proteins (KIFs) in the prelimbic cortex for their role in mediating contextual fear, a form of associative memory. KIFs function as critical mediators of synaptic transmission and plasticity by their ability to modulate microtubule function and transport of gene products. However, the regulation and function of KIFs in the prelimbic cortex insofar as mediating memory consolidation is not known. We find that within one hour of contextual fear conditioning, the expression of KIF3B is upregulated in the prelimbic but not the infralimbic cortex. Importantly, lentiviral-mediated knockdown of KIF3B in the prelimbic cortex produces deficits in consolidation while reducing freezing behavior during extinction of contextual fear. We also find that the depletion of KIF3B increases spine density within prelimbic neurons. Taken together, these results illuminate a key role for KIF3B in the prelimbic cortex as far as mediating contextual fear memory.

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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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