Function and Regulation of CREB Family Transcription Factors in the Nervous System

Flavonoids: antioxidants or signalling molecules?

Lynch, MA. Long-Term Potentiation and Memory. Physiol Rev 84: 87–136, 2004; 10.1152/physrev.00014.2003.—One of the most significant challenges in neuroscience is to identify the cellular and molecu...

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Long-Term Potentiation and Memory

Neural Mechanisms of Extinction Learning and Retrieval

Optimizing inhibitory learning during exposure therapy

A Role for the PI-3 kinase signaling pathway in fear conditioning and synaptic plasticity in the amygdala

Memory extinction refers to a gradual decrease of the previously acquired response when exposed to conditional stimulus without pairing with unconditional stimulus. Here we show for the first time that fear training-induced phosphorylation of specific substrates in the rat amygdala is reduced after extinction trials and is accompanied by an increase in the protein level and enzymatic activity of calcineurin. In parallel, calcineurin inhibitors prevented extinction-induced protein dephosphorylation as well as extinction of fear memory. Thus, extinction training increased phosphatase activity likely via an expression of calcineurin. Calcineurin then created a negative-feedback loop and directly or indirectly dephosphorylated specific substrates, which, in their phosphorylated state, were required for memory consolidation. Accordingly, in our experimental condition, extinction could be ascribed at least in part to a weakening of the original signaling.

https://www.jneurosci.org/content/jneuro/23/5/1574.full.pdf

Identification of Calcineurin as a Key Signal in the Extinction of Fear Memory

Cancellation of low-frequency stimulation-induced long-term depression by docosahexaenoic acid in the rat hippocampus

Potentiation of N-methyl-d-aspartate currents by isoproterenol in the acutely dissociated rat amygdalar neurons

The modulation of voltage-dependent calcium currents (I(Ca)) by serotonin (5-HT) was studied in rat acutely dissociated amygdala neurons using whole-cell patch-clamp recording techniques. 5-HT inhibited I(Ca) in a concentration-dependent manner with a ED50 of approximately 1 microM and a maximal inhibition of approximately 50%. The inhibition was mimicked by the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and was reduced by the 5-HT1A antagonist NAN-190, indicating its mediation by 5-HT1A receptors. Pretreatment of neurons with the alkylating agent N-ethylmaleimide (NEM) or pertussis toxin (PTX) markedly reduced the action of 5-HT. The modulation was partially reversed by strong depolarization and was not seen in cell-attached patches when the agonist was applied outside the recorded patch, suggesting a membrane-delimited, G-protein-mediated signaling pathway. Nimodipine (1 microM) reduced the I(Ca) by approximately 30% without reducing inhibition of current by 5-HT significantly, ruling out L-type channels as the target of modulation. 5-HT-mediated inhibition after exposure to omega-conotoxin-GVIA (omega-CgTX, 1 microM) or omega-agatoxin-IV (omega-AgTX, 200 nM), which blocked 26% and 21% of the total I(Ca), respectively, was significantly decreased, suggesting involvement of the N- and P/Q-type channels. In the combined presence of omega-CgTX and omega-AgTX, 5-HT still caused a small but significant reduction of I(Ca), suggesting a possible involvement of R-type channels. Stimulation of beta-adrenergic receptor with isoproterenol (Iso) or activation of adenylyl cyclase with forskolin resulted in an enhancement of I(Ca). 5-HT caused the same degree of inhibition with or without Iso or forskolin pretreatment. On the other hand, application of 8-OH-DPAT inhibited I(Ca) and blocked Iso- and Sp-cAMPS-induced enhancement. These results provide the first evidence showing a dominant effect of 5-HT-mediated inhibition over Iso-mediated enhancement of I(Ca).

Chih Hung Lin

Papers

A Role for the PI-3 kinase signaling pathway in fear conditioning and synaptic plasticity in the amygdala

Identification of Calcineurin as a Key Signal in the Extinction of Fear Memory

Cancellation of low-frequency stimulation-induced long-term depression by docosahexaenoic acid in the rat hippocampus

Potentiation of N-methyl-d-aspartate currents by isoproterenol in the acutely dissociated rat amygdalar neurons

Modulation of voltage-dependent calcium currents by serotonin in acutely isolated rat amygdala neurons