Short-term inhibition of 11β-hydroxysteroid dehydrogenase type 1 reversibly improves spatial memory but persistently impairs contextual fear memory in aged mice

Exposure to volatile anesthetics during the neonatal period results in acute neuron death. Prior work suggests that apoptosis is the dominant mechanism mediating neuron death. We show that Bax deficiency blocks neuronal death following exposure to isoflurane during the neonatal period. Blocking Bax-mediated neuron death attenuated the neuroinflammatory response of microglia following isoflurane exposure. We find that GABAergic interneurons are disproportionately overrepresented among dying neurons. Despite the increase in neuronal apoptosis induced by isoflurane exposure during the neonatal period, seizure susceptibility, spatial memory retention, and contextual fear memory were unaffected later in life. However, Bax deficiency alone led to mild deficiencies in spatial memory and contextual fear memory, suggesting that normal developmental apoptotic death is important for cognitive function. Collectively, these findings show that while GABAergic neurons in the neonatal brain undergo elevated Bax-dependent apoptotic cell death following exposure to isoflurane, this does not appear to have long-lasting consequences on overall neurological function later in life.

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Contextual Fear Memory Formation and Destabilization Induce Hippocampal RyR2 Calcium Channel Upregulation

Neural Plasticity ◽

10.1155/2018/5056181 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11

Author(s):

Jamileth More ◽

María Mercedes Casas ◽

Gina Sánchez ◽

Cecilia Hidalgo ◽

Paola Haeger

Keyword(s):

Spatial Memory ◽

Fear Memory ◽

Contextual Fear Conditioning ◽

Male Rats ◽

Endoplasmic Reticulum Membrane ◽

Memory Retention ◽

Contextual Fear ◽

Memory Processes ◽

Contextual Fear Memory ◽

Protein Levels

Hippocampus-dependent spatial and aversive memory processes entail Ca2+ signals generated by ryanodine receptor (RyR) Ca2+ channels residing in the endoplasmic reticulum membrane. Rodents exposed to different spatial memory tasks exhibit significant hippocampal RyR upregulation. Contextual fear conditioning generates robust hippocampal memories through an associative learning process, but the effects of contextual fear memory acquisition, consolidation, or extinction on hippocampal RyR protein levels remain unreported. Accordingly, here we investigated if exposure of male rats to contextual fear protocols, or subsequent exposure to memory destabilization protocols, modified the hippocampal content of type-2 RyR (RyR2) channels, the predominant hippocampal RyR isoforms that hold key roles in synaptic plasticity and spatial memory processes. We found that contextual memory retention caused a transient increase in hippocampal RyR2 protein levels, determined 5 h after exposure to the conditioning protocol; this increase vanished 29 h after training. Context reexposure 24 h after training, for 3, 15, or 30 min without the aversive stimulus, decreased fear memory and increased RyR2 protein levels, determined 5 h after reexposure. We propose that both fear consolidation and extinction memories induce RyR2 protein upregulation in order to generate the intracellular Ca2+ signals required for these distinct memory processes.

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