Hippocampal c-Jun-N-Terminal Kinases Serve as Negative Regulators of Associative Learning

Sherrin, Tessi; Blank, Thomas; Hippel, Cathrin; Rayner, Martin D.; Davis, Roger J.; Todorovic, Cedomir

doi:10.1523/jneurosci.3492-10.2010

Cited by 62 publications

(57 citation statements)

References 89 publications

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“…Pharmacological inhibition of the JNKs immediately after conditioning enhances contextual fear mediumterm memory (MTM) but not STM (Sherrin et al 2010; see also Bevilaqua et al 2003). Consistent with this, psychological stress effects that impair contextual fear LTM formation are mediated by JNK2 and JNK3 (Sherrin et al 2010). Thus, JNK activation negatively regulates LTM formation.…”

Section: Mapk Familymentioning

confidence: 64%

“…Contextual fear conditioning induces the activation 1 h after, but not 30 min after, conditioning and JNK activity returns to baseline within 8 h (Sherrin et al 2010). Pharmacological inhibition of the JNKs immediately after conditioning enhances contextual fear mediumterm memory (MTM) but not STM (Sherrin et al 2010; see also Bevilaqua et al 2003). Consistent with this, psychological stress effects that impair contextual fear LTM formation are mediated by JNK2 and JNK3 (Sherrin et al 2010).…”

Section: Mapk Familymentioning

confidence: 82%

“…Finally, JNKs also become activated during hippocampal memory formation. Contextual fear conditioning induces the activation 1 h after, but not 30 min after, conditioning and JNK activity returns to baseline within 8 h (Sherrin et al 2010). Pharmacological inhibition of the JNKs immediately after conditioning enhances contextual fear mediumterm memory (MTM) but not STM (Sherrin et al 2010; see also Bevilaqua et al 2003).…”

Section: Mapk Familymentioning

confidence: 99%

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The roles of protein kinases in learning and memory

2013

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In the adult mammalian brain, more than 250 protein kinases are expressed, but only a few of these kinases are currently known to enable learning and memory. Based on this information it appears that learning and memory-related kinases either impact on synaptic transmission by altering ion channel properties or ion channel density, or regulate gene expression and protein synthesis causing structural changes at existing synapses as well as synaptogenesis. Here, we review the roles of these kinases in short-term memory formation, memory consolidation, memory storage, retrieval, reconsolidation, and extinction. Specifically, we discuss the roles of calcium/calmodulin-dependent kinase II (CaMKII

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Section: Mapk Familymentioning

confidence: 64%

Section: Mapk Familymentioning

confidence: 82%

Section: Mapk Familymentioning

confidence: 99%

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The roles of protein kinases in learning and memory

2013

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“…It is possible that DLK also induces neuronal degeneration in chronic paradigms such as Alzheimer's disease, Parkinson's disease, or even environmental stresses. Indeed, there is precedence for JNK pathway activation and function in each of these instances (Saporito et al, 1999;Morishima et al, 2001;Hunot et al, 2004;Thakur et al, 2007;Sherrin et al, 2010), all of which have the potential to be DLK dependent. revealed a decrease (80-fold) in total levels of Fluoro-Jade C staining in DLK lox ;Cre pos mice after kainic acid treatment (Fig.…”

Section: Loss Of Dlk Protects Neurons Against Excitotoxicity-induced mentioning

confidence: 99%

Dual leucine zipper kinase is required for excitotoxicity induced neuronal degeneration

Pozniak¹,

Ghosh²,

Gogineni³

et al. 2013

J Cell Biol

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Excessive glutamate signaling is thought to underlie neurodegeneration in multiple contexts, yet the pro-degenerative signaling pathways downstream of glutamate receptor activation are not well defined. We show that dual leucine zipper kinase (DLK) is essential for excitotoxicity-induced degeneration of neurons in vivo. In mature neurons, DLK is present in the synapse and interacts with multiple known postsynaptic density proteins including the scaffolding protein PSD-95. To examine DLK function in the adult, DLK-inducible knockout mice were generated through Tamoxifen-induced activation of Cre-ERT in mice containing a floxed DLK allele, which circumvents the neonatal lethality associated with germline deletion. DLK-inducible knockouts displayed a modest increase in basal synaptic transmission but had an attenuation of the JNK/c-Jun stress response pathway activation and significantly reduced neuronal degeneration after kainic acid-induced seizures. Together, these data demonstrate that DLK is a critical upstream regulator of JNK-mediated neurodegeneration downstream of glutamate receptor hyper-activation and represents an attractive target for the treatment of indications where excitotoxicity is a primary driver of neuronal loss.

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“…U0126 was from Cell Signaling, while DJNK-1 was the kind gift of Dr. Tessi Sherrin (University of Hawaii). Both reagents were used at concentrations effecting full inhibition, as based on previous reports (25). All common reagents (e.g.…”

Section: Methodsmentioning

confidence: 99%