ERK Plays a Regulatory Role in Induction of LTP by Theta Frequency Stimulation and Its Modulation by β-Adrenergic Receptors

Winder, Danny G.; Martin, Kelsey C.; Muzzio, Isabel A.; Rohrer, Daniel K.; Chruscinski, Andrzej; Kobilka, Brian K.; Kandel, Eric R.

doi:10.1016/s0896-6273(00)81124-1

Cited by 301 publications

(360 citation statements)

References 54 publications

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“…Putative mechanisms for theta-frequency LTP have been described previously (Blitzer et al, 1995(Blitzer et al, , 1998Thomas et al, 1996;Winder et al, 1999), but the basis for the AU-AI difference in 5 Hz LTP that we report is not known. One possible scenario could involve a difference in calcium channel signaling.…”

Section: Discussionmentioning

confidence: 53%

Theta-Frequency Synaptic Potentiation in CA1In VitroDistinguishes Cognitively Impaired from Unimpaired Aged Fischer 344 Rats

et al. 2002

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Hippocampal-dependent learning and memory deficits have been well documented in aging rodents. The results of several recent studies have suggested that these deficits arise from weakened synaptic plasticity within the hippocampus. In the present study, we examined the relationship between hippocampal long-term potentiation (LTP) in vitro and spatial learning in aged (24-26 months) Fischer 344 rats. We found that LTP induced in the CA1 region using theta-frequency stimulation (5 Hz) is selectively impaired in slices from a subpopulation of aged rats that had shown poor spatial learning in the Morris water maze. LTP at 5 Hz in aged rats that did not show learning deficits was similar to that seen in young (4-6 months) controls. We also found that 5 Hz LTP amplitude strongly correlated with individual learning performance among aged rats. The difference in 5 Hz LTP magnitude among aged rats was not attributable to an altered response to 5 Hz stimulation or to differences in the NMDA receptormediated field EPSP. In addition, no performance-related differences in LTP were seen when LTP was induced with 30 or 70 Hz stimulation protocols. Finally, both 5 Hz LTP and spatial learning in learning-impaired rats were enhanced with the selective muscarinic M 2 antagonist ]benzodiazepin-6-one). These findings reinforce the idea that distinct types of hippocampal LTP offer mechanistic insight into age-associated cognitive decline.

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Section: Discussionmentioning

confidence: 53%

Theta-Frequency Synaptic Potentiation in CA1In VitroDistinguishes Cognitively Impaired from Unimpaired Aged Fischer 344 Rats

et al. 2002

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“…A possible explanation for differences between the in vivo and slice work is the absence of neuromodulatory signals in the slices. NMDA-receptor-dependent synaptic plasticity often requires additional signals through neuromodulatory receptors such as the Gs-coupled β1 adrenergic receptor (Thomas et al, 1996;Winder et al, 1999). In fact, preliminary data with β1 adrenergic stimulation of slices have demonstrated a rapid translation of STEP within 10 minutes (Hu and Lombroso, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

The Striatal-Enriched Protein Tyrosine Phosphatase Gates Long-Term Potentiation and Fear Memory in the Lateral Amygdala

Paul

Olausson

Venkitaramani

et al. 2007

Biological Psychiatry

100

116

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“…Stimulation of CB1-Rs activates ERK, a protein kinase known to be critical in several forms of synaptic plasticity and in learning and memory (English and Sweatt, 1997;Atkins et al, 1998). The ERK pathway appears essential for some forms of LTP in hippocampus (Winder et al, 1999) and for the regulation of gene expression in the context of synaptic plasticity (Impey et al, 1999). Remarkably, the activation of ERK by THC was absent in the hippocampus of mice lacking the tyrosine kinase Fyn, which display altered synaptic plasticity (Grant et al, 1992).…”

Section: Functional Implications Of the Regulation Of Erk And Immediamentioning

confidence: 99%

Regulation of Extracellular Signal-Regulated Kinase by Cannabinoids in Hippocampus

et al. 2003

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Endocannabinoids form a novel class of intercellular messengers, the functions of which include retrograde signaling in the brain and mediation or modulation of several types of synaptic plasticity. Yet, the signaling mechanisms and long-term effects of the stimulation of CB1 cannabinoid receptors (CB1-R) are poorly understood. We show that anandamide, 2-arachidonoyl-glycerol, and ⌬9-tetrahydrocannabinol (THC) activated extracellular signal-regulated kinase (ERK) in hippocampal slices. In living mice, THC activated ERK in hippocampal neurons and induced its accumulation in the nuclei of pyramidal cells in CA1 and CA3. Both effects were attributable to stimulation of CB1-R and activation of MAP kinase/ERK kinase (MEK). In hippocampal slices, the stimulation of ERK was independent of phosphatidyl-inositol-3-kinase but was regulated by cAMP. The endocannabinoid-induced stimulation of ERK was lost in Fyn knockout mice, in slices and in vivo, although it was insensitive to inhibitors of Src-family tyrosine kinases in vitro, suggesting a noncatalytic role of Fyn. Finally, the effects of cannabinoids on ERK activation were dependent on the activity of glutamate NMDA receptors in vivo, but not in hippocampal slices, indicating the existence of several pathways linking CB1-R to the ERK cascade. In vivo THC induced the expression of immediate-early genes products (c-Fos protein, Zif268, and BDNF mRNAs), and this induction was prevented by an inhibitor of MEK. The strong potential of cannabinoids for inducing long-term alterations in hippocampal neurons through the activation of the ERK pathway may be important for the physiological control of synaptic plasticity and for the general effects of THC in the context of drug abuse.

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ERK Plays a Regulatory Role in Induction of LTP by Theta Frequency Stimulation and Its Modulation by β-Adrenergic Receptors

Cited by 301 publications

References 54 publications

Theta-Frequency Synaptic Potentiation in CA1In VitroDistinguishes Cognitively Impaired from Unimpaired Aged Fischer 344 Rats

Theta-Frequency Synaptic Potentiation in CA1In VitroDistinguishes Cognitively Impaired from Unimpaired Aged Fischer 344 Rats

The Striatal-Enriched Protein Tyrosine Phosphatase Gates Long-Term Potentiation and Fear Memory in the Lateral Amygdala

Regulation of Extracellular Signal-Regulated Kinase by Cannabinoids in Hippocampus

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