Context-driven cocaine-seeking in abstinent rats increases activity-regulated gene expression in the basolateral amygdala and dorsal hippocampus differentially following short and long periods of abstinence

Extinction of conditioned fear necessitates the dynamic involvement of hippocampus, medial prefrontal cortex (mPFC), and basolateral amygdala (BLA), but key molecular players that regulate these circuits to achieve fear extinction remain largely unknown. Here, we report that acid-sensing ion channel 1a (ASIC1a) is a crucial molecular regulator of fear extinction, and that this function requires ASIC1a in ventral hippocampus (vHPC), but not dorsal hippocampus, mPFC, or BLA. While genetic disruption or pharmacological inhibition of ASIC1a in vHPC attenuated the extinction of conditioned fear, overexpression of the channel in this area promoted fear extinction. Channelrhodopsin-2–assisted circuit mapping revealed that fear extinction involved an ASIC1a-dependent modification of the long-range hippocampal-prefrontal correlates in a projection-specific manner. Gene expression profiling analysis and validating experiments identified several neuronal activity–regulated and memory-related genes, including Fos, Npas4, and Bdnf, as the potential mediators of ASIC1a regulation of fear extinction. Mechanistically, genetic overexpression of brain-derived neurotrophic factor (BDNF) in vHPC or supplement of BDNF protein in mPFC both rescued the deficiency in fear extinction and the deficits on extinction-driven adaptations of hippocampal-prefrontal correlates caused by the Asic1a gene inactivation in vHPC. Together, these results establish ASIC1a as a critical constituent in fear extinction circuits and thus a promising target for managing adaptive behaviors.

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Interaction between the basolateral amygdala and dorsal hippocampus is critical for cocaine memory reconsolidation and subsequent drug context-induced cocaine-seeking behavior in rats

Learning & Memory ◽

10.1101/lm.2273111 ◽

2011 ◽

Vol 18 (11) ◽

pp. 693-702 ◽

Cited By ~ 47

Author(s):

A. M. Wells ◽

H. C. Lasseter ◽

X. Xie ◽

K. E. Cowhey ◽

A. M. Reittinger ◽

...

Keyword(s):

Basolateral Amygdala ◽

Dorsal Hippocampus ◽

Memory Reconsolidation ◽

Cocaine Seeking ◽

Seeking Behavior

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Nutrient-regulated gene expression in eukaryotes

Biochemical Society Symposium ◽

10.1042/bss0730085 ◽

2006 ◽

Vol 73 ◽

pp. 85-96 ◽

Cited By ~ 8

Author(s):

Richard J. Reece ◽

Laila Beynon ◽

Stacey Holden ◽

Amanda D. Hughes ◽

Karine Rébora ◽

...

Keyword(s):

Gene Expression ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Transcriptional Control ◽

Direct Interaction ◽

Signalling Pathways ◽

A Cell ◽

One Step ◽

Higher Eukaryotes ◽

Regulated Gene Expression

The recognition of changes in environmental conditions, and the ability to adapt to these changes, is essential for the viability of cells. There are numerous well characterized systems by which the presence or absence of an individual metabolite may be recognized by a cell. However, the recognition of a metabolite is just one step in a process that often results in changes in the expression of whole sets of genes required to respond to that metabolite. In higher eukaryotes, the signalling pathway between metabolite recognition and transcriptional control can be complex. Recent evidence from the relatively simple eukaryote yeast suggests that complex signalling pathways may be circumvented through the direct interaction between individual metabolites and regulators of RNA polymerase II-mediated transcription. Biochemical and structural analyses are beginning to unravel these elegant genetic control elements.

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FNR and its role in oxygen-regulated gene expression in

FEMS Microbiology Reviews ◽

10.1016/s0168-6445(05)80007-5 ◽

1990 ◽

Vol 75 (4) ◽

pp. 399-428 ◽

Cited By ~ 82

Author(s):

S SPIRO ◽

J GUEST

Keyword(s):

Gene Expression ◽

Regulated Gene Expression

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Stage 1 Registered Report Manuscript - Transcriptional Correlates of Savings Memory: Is Forgetting Due to Decay or Retrieval Failure?

10.31234/osf.io/s7dft ◽

2020 ◽

Author(s):

Robert Calin-Jageman ◽

Irina Calin-Jageman ◽

Tania Rosiles ◽

Melissa Nguyen ◽

Annette Garcia ◽

...

Keyword(s):

Gene Expression ◽

Memory Trace ◽

Aplysia Californica ◽

Retrieval Failure ◽

Initial Learning ◽

Rigorous Test ◽

Regulated Gene Expression ◽

Stage 1 ◽

Weak Similarity

[[This is a Stage 1 Registered Report manuscript. The project was submitted for review to eNeuro. Upon revision and acceptance, this version of the manuscript was pre-registered on the OSF (9/11/2019, https://osf.io/fqh8j) (but due to an oversight not posted as a preprint until July 2020). A Stage 2 manuscript is now posted as a pre-print (https://psyarxiv.com/h59jv) and is under review at eNeuro. A link to the final Stage 2 manuscript will be added when available.]]There is fundamental debate about the nature of forgetting: some have argued that it represents the decay of the memory trace, others that the memory trace persists but becomes inaccessible due to retrieval failure. These different accounts of forgetting make different predictions about savings memory, the rapid re-learning of seemingly forgotten information. If forgetting is due to decay then savings requires re-encoding and should thus involve the same mechanisms as initial learning. If forgetting is due to retrieval-failure then savings should be mechanistically distinct from encoding. In this registered report we conducted a pre-registered and rigorous test between these accounts of forgetting. Specifically, we used microarray to characterize the transcriptional correlates of a new memory (1 day from training), a forgotten memory (8 days from training), and a savings memory (8 days from training but with a reminder on day 7 to evoke a long-term savings memory) for sensitization in Aplysia californica (n = 8 samples/group). We find that the transcriptional correlates of savings are [highly similar / somewhat similar / unique] relative to new (1-day-old) memories. Specifically, savings memory and a new memory share [X] of [Y] regulated transcripts, show [strong / moderate / weak] similarity in sets of regulated transcripts, and show [r] correlation in regulated gene expression, which is [substantially / somewhat / not at all] stronger than at forgetting. Overall, our results suggest that forgetting represents [decay / retrieval-failure / mixed mechanisms].

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