The role of carbonic anhydrases in extinction of contextual fear memory

Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in mammals with 16 isoforms that differ in terms of catalytic activity as well as cellular and tissue distribution. CAs catalyze the conversion of CO2to bicarbonate and protons and are involved in various physiological processes, including learning and memory. Here we report that the integrity of CA activity in the brain is necessary for the consolidation of fear extinction memory. We found that systemic administration of acetazolamide, a CA inhibitor, immediately after the extinction session dose-dependently impaired the consolidation of fear extinction memory of rats trained in contextual fear conditioning.d-phenylalanine, a CA activator, displayed an opposite action, whereas C18, a membrane-impermeable CA inhibitor that is unable to reach the brain tissue, had no effect. Simultaneous administration of acetazolamide fully prevented the procognitive effects ofd-phenylalanine. Whereasd-phenylalanine potentiated extinction, acetazolamide impaired extinction also when infused locally into the ventromedial prefrontal cortex, basolateral amygdala, or hippocampal CA1 region. No effects were observed when acetazolamide ord-phenylalanine was infused locally into the substantia nigra pars compacta. Moreover, systemic administration of acetazolamide immediately after the extinction training session modulated c-Fos expression on a retention test in the ventromedial prefrontal cortex of rats trained in contextual fear conditioning. These findings reveal that the engagement of CAs in some brain regions is essential for providing the brain with the resilience necessary to ensure the consolidation of extinction of emotionally salient events.

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NR2A- and NR2B-containing NMDA receptors in the prelimbic medial prefrontal cortex differentially mediate trace, delay, and contextual fear conditioning

Learning & Memory ◽

10.1101/lm.030510.113 ◽

2013 ◽

Vol 20 (6) ◽

pp. 290-294 ◽

Cited By ~ 42

Author(s):

M. R. Gilmartin ◽

J. L. Kwapis ◽

F. J. Helmstetter

Keyword(s):

Prefrontal Cortex ◽

Nmda Receptors ◽

Fear Conditioning ◽

Medial Prefrontal Cortex ◽

Contextual Fear Conditioning ◽

Contextual Fear

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Translational Research from Animals to Humans

10.1093/med/9780190215422.003.0017 ◽

2016 ◽

Author(s):

Shigeru Morinobu ◽

Shigeto Yamamoto ◽

Manabu Fuchikami

Keyword(s):

Animal Model ◽

Fear Conditioning ◽

Fear Extinction ◽

Contextual Fear Conditioning ◽

Behavioral Characteristics ◽

Post Traumatic Stress ◽

Contextual Fear ◽

Glycine Transporter 1 ◽

Post Traumatic ◽

Prolonged Stress

To elucidate the pathophysiology of post-traumatic stress disorder (PTSD), the establishment of an appropriate animal model is necessary. In a series of studies, the authors validated single prolonged stress (SPS) as a model for PTSD. SPS-treated rats mimic the pathophysiological abnormalities and behavioral characteristics of PTSD, such as enhanced anxiety-like behavior, glucocorticoid negative feedback, and analgesia. In addition, the authors demonstrated enhanced freezing in response to contextual fear conditioning, and impaired extinction of fear memory, which was alleviated by D-cycloserine (DCS). In parallel, there was a decrease in extracellular glycine mediated by an increase in glycine transporter 1 in the hippocampus of SPS-treated rats after fear conditioning, which suggested that activation of N-methyl-D-asparate receptor by DCS during fear extinction training might alleviate the impaired fear extinction. This chapter summarizes PTSD-like symptoms in SPS and evaluates the validity of SPS as an animal model of PTSD.

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M3 muscarinic receptor in the ventral medial prefrontal cortex modulating the expression of contextual fear conditioning in rats

Psychopharmacology ◽

10.1007/s00213-015-4109-5 ◽

2015 ◽

Vol 233 (2) ◽

pp. 267-280 ◽

Cited By ~ 6

Author(s):

A. G. Fedoce ◽

N. C. Ferreira-Junior ◽

D. G. Reis ◽

F. M. A. Corrêa ◽

L. B. M. Resstel

Keyword(s):

Prefrontal Cortex ◽

Fear Conditioning ◽

Muscarinic Receptor ◽

Medial Prefrontal Cortex ◽

Contextual Fear Conditioning ◽

Contextual Fear ◽

Ventral Medial Prefrontal Cortex ◽

M3 Muscarinic Receptor

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Variants of contextual fear conditioning induce differential patterns of Egr-1 activity within the young adult prefrontal cortex

Behavioural Brain Research ◽

10.1016/j.bbr.2016.01.018 ◽

2016 ◽

Vol 302 ◽

pp. 122-130 ◽

Cited By ~ 14

Author(s):

T. Chakraborty ◽

A. Asok ◽

M.E. Stanton ◽

J.B. Rosen

Keyword(s):

Prefrontal Cortex ◽

Young Adult ◽

Fear Conditioning ◽

Contextual Fear Conditioning ◽

Contextual Fear

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Systemic Administration of γ-Hydroxybutyric Acid in Adolescent Rat Impairs Contextual Fear Conditioning, But Not Cued Conditioning

Journal of Drug and Alcohol Research ◽

10.4303/jdar/235801 ◽

2014 ◽

Vol 3 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Ratna Sircar ◽

Keita Ishiwari

Keyword(s):

Fear Conditioning ◽

Systemic Administration ◽

Contextual Fear Conditioning ◽

Hydroxybutyric Acid ◽

Contextual Fear

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Trace and contextual fear conditioning are impaired following unilateral microinjection of muscimol in the ventral hippocampus or amygdala, but not the medial prefrontal cortex

Neurobiology of Learning and Memory ◽

10.1016/j.nlm.2012.03.009 ◽

2012 ◽

Vol 97 (4) ◽

pp. 452-464 ◽

Cited By ~ 49

Author(s):

Marieke R. Gilmartin ◽

Janine L. Kwapis ◽

Fred J. Helmstetter

Keyword(s):

Prefrontal Cortex ◽

Fear Conditioning ◽

Medial Prefrontal Cortex ◽

Ventral Hippocampus ◽

Contextual Fear Conditioning ◽

Contextual Fear

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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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