Neurogenesis-induced forgetting is associated with reduced neuronal activity in CA1 during context fear memory retrieval

Mapping Intimacies ◽

10.1101/2021.03.24.436893 ◽

2021 ◽

Author(s):

Alexandria Evans ◽

Gavin A. Scott ◽

Jonathan R. Epp

Keyword(s):

Memory Retrieval ◽

Wheel Running ◽

Fear Memory ◽

Hippocampal Neurogenesis ◽

Contextual Fear Conditioning ◽

Early Gene ◽

Population Activity ◽

Contextual Fear ◽

Induced Forgetting

AbstractHippocampal neurogenesis has a role in many essential learning and memory processes, including forgetting. This forgetting process is important because it prevents proactive interference between old and new memories. While several studies have now established the role of neurogenesis in forgetting, the specific mechanisms mediating neurogenesis-induced forgetting have not been elucidated. The goal of this study was to examine how increased neurogenesis affects the recall of context fear memory in addition to its effects on population activity within hippocampal subregions. We trained mice in contextual fear conditioning and then increased neurogenesis via 4 weeks of voluntary wheel running. Increased neurogenesis led to a reduction in freezing behaviour during context testing, replicating previous studies showing that increased neurogenesis causes forgetting of context fear memories. Additionally, we mapped the expression of the immediate early gene c-Fos within hippocampal subregions and found that increasing neurogenesis led to reduced CA1 c-Fos expression during context testing. The results suggest that reduced CA1 population activity may underlie the association between increased neurogenesis and forgetting.

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Analyzing the role of adult hippocampal neurogenesis in contextual fear conditioning

Frontiers in Behavioral Neuroscience ◽

10.3389/conf.neuro.08.2009.09.022 ◽

2009 ◽

Vol 3 ◽

Author(s):

Hen Rene

Keyword(s):

Fear Conditioning ◽

Hippocampal Neurogenesis ◽

Contextual Fear Conditioning ◽

Adult Hippocampal Neurogenesis ◽

Contextual Fear

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Limited replicability of drug-induced amnesia after contextual fear memory retrieval in rats

10.31234/osf.io/akz6b ◽

2019 ◽

Author(s):

Natalie Schroyens ◽

Joaquin Matias Alfei Palloni ◽

Anna Elisabeth Schnell ◽

Laura Luyten ◽

Tom Beckers

Keyword(s):

Memory Retrieval ◽

Fear Memory ◽

Contextual Fear Conditioning ◽

Memory Retention ◽

Conditioning Context ◽

Drug Induced ◽

Systemic Injection ◽

Contextual Fear ◽

Contextual Fear Memory ◽

Systemic Drug

With the ultimate goal of investigating boundary conditions for post-reactivation amnesia, we set out to replicate studies in which systemic, post-reactivation administration of midazolam, propranolol, or cycloheximide resulted in amnesia for contextual fear memories. Our experiments involved conceptual as well as exact replications of previously published studies. In most of our experiments, we adopted a procedure that conformed to the standard 3-day protocol typically used in the literature, with contextual fear conditioning on day 1, unreinforced re-exposure to the conditioning context followed by systemic injection of the amnestic drug on day 2, and a memory retention test on day 3. Given the plethora of successful studies with large effects sizes and the absence of any failed replications in the literature, we were surprised to find that we were generally unable to replicate those findings. Our results suggest that post-reactivation amnesia by systemic drug administration in rats is more difficult to obtain than what would be expected based on published empirical reports. At present, it remains unclear which conditions determine the success of this procedure.

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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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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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