scholarly journals The Role of the Entorhinal Cortex in Extinction: Influences of Aging

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Lia R. M. Bevilaqua ◽  
Janine I. Rossato ◽  
Juliana S. Bonini ◽  
Jociane C. Myskiw ◽  
Julia R. Clarke ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Entorhinal Cortex ◽  
Amyloid Plaques ◽  
Memory Formation ◽  
Amygdaloid Nucleus ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Glutamate Nmda Receptors ◽  
The Brain

The entorhinal cortex is perhaps the area of the brain in which neurofibrillary tangles and amyloid plaques are first detectable in old age with or without mild cognitive impairment, and very particularly in Alzheimer's disease. It plays a key role in memory formation, retrieval, and extinction, as part of circuits that include the hippocampus, the amygdaloid nucleus, and several regions of the neocortex, in particular of the prefrontal cortex. Lesions or biochemical impairments of the entorhinal cortex hinder extinction. Microinfusion experiments have shown that glutamate NMDA receptors, calcium and calmodulin-dependent protein kinase II, and protein synthesis in the entorhinal cortex are involved in and required for extinction. Aging also hinders extinction; it is possible that its effect may be in part mediated by the entorhinal cortex.

Hippocampal-prefrontal theta coupling develops as mice become proficient in associative odorant discrimination learning

2021 ◽  
Author(s):  
Daniel Ramirez-Gordillo ◽  
Andrew A. Parra ◽  
K. Ulrich Bayer ◽  
Diego Restrepo
Keyword(s):  
Learning And Memory ◽  
Discrimination Learning ◽  
Gamma Oscillations ◽  
Oscillatory Activity ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Theta Phase ◽  
Phase Amplitude ◽  
The Brain

Learning and memory requires coordinated activity between different regions of the brain. Here we studied the interaction between medial prefrontal cortex (mPFC) and hippocampal dorsal CA1 during associative odorant discrimination learning in the mouse. We found that as the animal learns to discriminate odorants in a go-no go task the coupling of high frequency neural oscillations to the phase of theta oscillations (phase-amplitude coupling or PAC) changes in a manner that results in divergence between rewarded and unrewarded odorant-elicited changes in the theta-phase referenced power (tPRP) for beta and gamma oscillations. In addition, in the proficient animal there was a decrease in the coordinated oscillatory activity between CA1 and mPFC in the presence of the unrewarded odorant. Furthermore, the changes in PAC resulted in a marked increase in the accuracy for decoding odorant identity from tPRP when the animal became proficient. Finally, we studied the role of Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα), a protein involved in learning and memory, in oscillatory neural processing in this task. We find that the accuracy for decoding the odorant identity from tPRP decreases in CaMKIIα knockout mice and that this accuracy correlates with behavioral performance. These results implicate a role for PAC and CaMKIIα in olfactory go-no go associative learning in the hippocampal-prefrontal circuit.

scholarly journals Phosphorylation of the α subunit of translation initiation factor-2 by PKR mediates protein synthesis inhibition in the mouse brain during status epilepticus

2006 ◽  
Vol 397 (1) ◽  
pp. 187-194 ◽  
Author(s):  
Larissa S. Carnevalli ◽  
Catia M. Pereira ◽  
Carolina B. Jaqueta ◽  
Viviane S. Alves ◽  
Vanessa N. Paiva ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Initiation Factor ◽  
Dependent Protein Kinase ◽  
Α Subunit ◽  
Eif2α Phosphorylation ◽  
Inhibition Of Protein Synthesis ◽  
Initiation Factor 2 ◽  
Dependent Protein ◽  
Eif2α Kinase ◽  
The Brain

In response to different cellular stresses, a family of protein kinases phosphorylates eIF2α (α subunit of eukaryotic initiation factor-2), contributing to regulation of both general and genespecific translation proposed to alleviate cellular injury or alternatively induce apoptosis. Recently, we reported eIF2α(P) (phosphorylated eIF2α) in the brain during SE (status epilepticus) induced by pilocarpine in mice, an animal model of TLE (temporal lobe epilepsy) [Carnevalli, Pereira, Longo, Jaqueta, Avedissian, Mello and Castilho (2004) Neurosci. Lett. 357, 191–194]. We show in the present study that one eIF2α kinase family member, PKR (double-stranded-RNA-dependent protein kinase), is activated in the cortex and hippocampus at 30 min of SE, reflecting the levels of eIF2α(P) in these areas. In PKR-deficient animals subjected to SE, eIF2α phosphorylation was clearly evident coincident with activation of a secondary eIF2α kinase, PEK/PERK (pancreatic eIF2α kinase/RNA-dependent-protein-kinase-like endoplasmic reticulum kinase), denoting a compensatory mechanism between the two kinases. The extent of eIF2α phosphorylation correlated with the inhibition of protein synthesis in the brain, as determined from polysome profiles. We also found that C57BL/6 mice, which enter SE upon pilocarpine administration but are more resistant to seizure-induced neuronal degeneration, showed very low levels of eIF2α(P) and no inhibition of protein synthesis during SE. These results taken together suggest that PKR-mediated phosphorylation of eIF2α contributes to inhibition of protein synthesis in the brain during SE and that sustained high levels of eIF2α phosphorylation may facilitate ensuing cell death in the most affected areas of the brain in TLE.

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