Infusing zeta inhibitory peptide into the perirhinal cortex of rats abolishes long-term object recognition memory without affecting novel object location recognition.

Infusing the amnesic agent zeta inhibitory peptide (ZIP) into the dorsal hippocampus disrupts established long-term object location recognition memory without affecting object identity recognition, which likely depends on the perirhinal cortex. Here, we tested whether infusing ZIP into the perirhinal cortex can abolish long-term memory supporting object identity recognition, leaving long-term object location recognition memory intact. We infused ZIP into the perirhinal cortex of rats either 1 day or 6 days after exposing them to two identical objects in an open field arena.

NMDA receptor activity bidirectionally controls active decay of long-term spatial memory in the dorsal hippocampus.

The time-dependent forgetting of long-term spatial memories involves activation of NMDA receptors (NMDARs) in the hippocampus. Here, we tested whether NMDARs regulate memory persistence bidirectionally, decreasing or increasing the rate of forgetting. We found that blocking NMDAR activation with AP5 or the GluN2B-selective antagonist Ro25-6981 in the dorsal hippocampus (dHPC) prevented the natural forgetting of long-term memory for the locations of objects in an open field arena.

Blocking Synaptic Removal of GluA2-Containing AMPA Receptors Prevents the Natural Forgetting of Long-Term Memories.

Unlabelled: The neurobiological processes underpinning the natural forgetting of long-term memories are poorly understood. Based on the critical role of GluA2-containing AMPA receptors (GluA2/AMPARs) in long-term memory persistence, we tested in rats whether their synaptic removal underpins time-dependent memory loss. We found that blocking GluA2/AMPAR removal with the interference peptides GluA23Y or G2CT in the dorsal hippocampus during a memory retention interval prevented the normal forgetting of established, long-term object location memories, but did not affect their acquisition.

Early expression of hypocretin/orexin in the chick embryo brain.

Hypocretin/Orexin (H/O) neuropeptides are released by a discrete group of neurons in the vertebrate hypothalamus which play a pivotal role in the maintenance of waking behavior and brain state control. Previous studies have indicated that the H/O neuronal development differs between mammals and fish; H/O peptide-expressing cells are detectable during the earliest stages of brain morphogenesis in fish, but only towards the end of brain morphogenesis (by ∼ 85% of embryonic development) in rats. The developmental emergence of H/O neurons has never been previously described in birds.

The maintenance of long-term memory in the hippocampus depends on the interaction between N-ethylmaleimide-sensitive factor and GluA2.

The maintenance of established memories has recently been shown to involve the stabilization of GluA2-containing AMPA receptors (GluA2/AMPARs) at postsynaptic membranes. Previous studies have suggested that N-ethylmaleimide-sensitive factor (NSF) regulates the stabilization of AMPARs at the synaptic membrane. We therefore disrupted the interaction between GluA2 and NSF in the dorsal hippocampus and examined its effect on the maintenance of object location and contextual fear memory.

PKMzeta maintains memories by regulating GluR2-dependent AMPA receptor trafficking.

The maintenance of long-term memory in hippocampus, neocortex and amygdala requires the persistent action of the atypical protein kinase C isoform, protein kinase Mzeta (PKMzeta). We found that inactivating PKMzeta in the amygdala impaired fear memory in rats and that the extent of the impairment was positively correlated with a decrease in postsynaptic GluR2. Blocking the GluR2-dependent removal of postsynaptic AMPA receptors abolished the behavioral impairment caused by PKMzeta inhibition and the associated decrease in postsynaptic GluR2 expression, which correlated with performance.

PKMzeta maintains 1-day- and 6-day-old long-term object location but not object identity memory in dorsal hippocampus.

Continuous activity of the atypical protein kinase C isoform M zeta (PKMzeta) is necessary for maintaining long-term memory acquired in aversively or appetitively motivated associative learning tasks, such as active avoidance, aversive taste conditioning, auditory and contextual fear conditioning, radial arm maze, and watermaze. Whether unreinforced, nonassociative memory will also require PKMzeta for long-term maintenance is not known. Using recognition memory for object location and object identity, we found that inactivating PKMzeta in dorsal hippocampus abolishes 1-day and 6-day-old long-term recognition memory for object location, while recognition memory for object identity was not affected by this treatment.

Biochemical, behavioural and electrophysiological investigations of brain maturation in chickens.

It is convenient to divide the development of synaptic networks into two phases: synapse formation during which synaptic contacts are established, and a subsequent maturation phase during which synaptic circuits are fine tuned and the properties of individual synapses are modified. Understanding the complex factors that control the protracted maturation process in humans is likely to be important for understanding a variety of neurological and psychiatric disorders. Chickens provide an ideal experimental model in which maturation specific changes can be identified and the mechanisms controlling them can be elucidated because the maturation phase is protracted and temporally separated from the formation phase.

Molecular changes in the intermediate medial mesopallium after a one trial avoidance learning in immature and mature chickens.

Because brain maturation in chickens is protracted and occurs well after the major developmental period of synaptogenesis, chicken forebrain is suitable to investigate whether the molecular mechanisms underlying memory consolidation are different in immature and mature animals. We have used antibodies and western blotting to analyze subcellular fractions from the intermediate medial mesopallium region of 14-day and 8-week chicken forebrain prepared 0, 45, and 120 min after learning a discriminative taste avoidance task. At both ages learning induced changes in the phosphorylation of the glutamate receptor subunit 1 at Ser831, the levels of calcium-calmodulin stimulated/dependent protein kinase II and the phosphorylation of calcium-calmodulin stimulated/dependent protein kinase II at Thr286 were observed only in the fraction enriched in post-synaptic densities.

Maturational changes in the subunit composition of AMPA receptors and the functional consequences of their activation in chicken forebrain.

AMPA receptors play a critical role in synaptic plasticity and brain development. Here we show that Ca(2+) uptake in response to AMPA receptor activation decreases dramatically during maturation in chicken brain microslices without a change in tissue AMPA receptor content. We found that during maturation the relative concentration of GluR2 subunits increased, the concentration of the AMPA receptor-associated scaffold proteins SAP97 and GRIP decreased and that depolarization increased GluR1 phosphorylation at Ser831 in subcellular fractions enriched in postsynaptic densities at 2 weeks but not at 10 weeks.

Phosphorylation of CaMKII at Thr253 occurs in vivo and enhances binding to isolated postsynaptic densities.

Autophosphorylation of Ca(2+)-calmodulin stimulated protein kinase II (CaMKII) at two sites (Thr286 and Thr305/306) is known to regulate the subcellular location and activity of this enzyme in vivo. CaMKII is also known to be autophosphorylated at Thr253 in vitro but the functional effect of phosphorylation at this site and whether it occurs in vivo, is not known. Using antibodies that specifically recognize CaMKII phosphorylated at Thr253 together with FLAG-tagged wild type and phospho- and dephospho-mimic mutants of alpha-CaMKII, we have shown that Thr253 phosphorylation has no effect on either the Ca(2+)-calmodulin dependent or autonomous kinase activity of recombinant alpha-CaMKII in vitro.

Sex differences in pregnenolone sulphate in the chick brain after training.

Pregnenolone and pregnenolone sulphate are potent memory enhancers when administered to rodents prior to various learning and memory paradigms. Here, we show that training on a passive avoidance task results in the increased concentration of pregnenolone sulphate in the medial striatum, formerly known as lobus parolfactorius of female but not male chicks. In addition, we demonstrated potential for neuronal synthesis of pregnenolone in the day-old chick brain, including in the intermediate medial mesopallium, formerly known as intermediate medial hyperstriatum ventrale and the medial striatum.

The crude extract from the sea anemone, Bunodosoma caissarum elicits convulsions in mice: possible involvement of the glutamatergic system.

The crude extract from the sea anemone, Bunodosoma caissarum caused dose-dependent convulsions by i.c.v.