Early Memory Phases Research Articles

Arginine kinase interacts with 2MIT and is involved in Drosophila melanogaster short-term memory

Mushroom bodies are a higher order center for sensory integration, learning and memory of the insect brain. Memory is generally subdivided into different phases. In the model organism Drosophila melanogaster, mushroom bodies have been shown to play a central role in both short- and long-term memory. In D. melanogaster, the gene 2mit codes a transmembrane protein carrying an extracellular Leucin-rich-repeat domain, which is highly transcribed in the mushroom and ellipsoid bodies of the adult fly brain and has a role in the early phase of memory. Utilizing coimmunoprecipitation experiments and mass spectrometry analyses, we have shown that 2MIT interacts with Arginine kinase in adult fly heads. Arginine kinase belongs to the family of Phosphagen kinases and plays a fundamental role in energy homeostasis. Using the GAL4/UAS binary system, we demonstrated that a downregulation of Arginine kinase mainly driven in the mushroom bodies affects short-term memory of Drosophila adult flies, in a courtship conditioning paradigm. As 2mit c03963 hypomorphic mutants showed comparable results when analyzed with the same assay, these data suggest that 2MIT and Arginine kinase are both involved in the same memory phenotype, likely interacting at the level of mushroom bodies. 2MIT and Arginine kinase are conserved among insects, the implications of which, along with their potential roles in other insect taxa are also discussed.

MiR-12 and miR-124 contribute to defined early phases of long-lasting and transient memory

MicroRNAs (miRNAs) are important epigenetic regulators of mRNA translation implicated in long-lasting synaptic plasticity and long-term memory (LTM). Since recent findings demonstrated a role of epigenetic regulation of gene expression in early memory phases we investigated whether epigenetic regulation by miRNAs also contributes to early memory phases. We used the olfactory associative learning paradigm in honeybees and addressed the contribution of miRNAs depending on the conditioning strength. We selected miR-12, miR-124, and miR-125 that have been implicated in processes of neuronal plasticity and analysed their contribution to non-associative and associative learning using miRNA inhibitors. Blocking miR-12, miR-124, or miR125 neither affects gustatory sensitivity nor habituation nor sensitization. Blocking the function of miR-12 and miR-124 during and shortly after 3-trial conditioning impairs different early memory phases. Although different, the function of miR-12 and miR-124 is also required for early phases of transient memory that is induced by 1-trial conditioning. Blocking miR-125 has no effect on early memory independent of the conditioning strength. These findings demonstrate that distinct miRNAs contribute to early phases of both, transient memories as well as long-lasting memories.

Early memory in the parasitoid wasp Nasonia vitripennis.

We studied early memory in Nasonia vitripennis, a parasitoid of fly pupae and emerging model organism for ecological questions in the context of learning. After associative training consisting of one drilling experience in a host in the presence of cinnamon, females showed a preference to cinnamon for at least 24 h. To study sensitisation, wasps were trained by one drilling in a host without cinnamon. These wasps were not attracted to cinnamon immediately afterwards. Obviously, sensitisation is not involved in early memory. Wasps that were anaesthetised by CO2 directly after associative training did not react to cinnamon 30-45 min later, but after 1 and 24 h. CO2 treatment≥5 min after training did not erase the reaction to cinnamon. This indicates the existence of four early memory phases. (a) One phase<5 min after training, in which CO2 has to be applied to become effective. (b) One subsequent phase which is resistant to CO2. (c) One phase<1 h in which memory can be erased by CO2 treatment directly after training. (d) One phase 1-24 h not affected by CO2 treatment. Together with earlier data this enables us to establish a complete memory structure for N. vitripennis.

Divided attention can enhance early-phase memory encoding: the attentional boost effect and study trial duration.

Divided attention during encoding typically produces marked reductions in later memory. The attentional boost effect (ABE) is a surprising variation on this phenomenon. In this paradigm, each study stimulus (e.g., a word) is presented along with a target or a distractor (e.g., different colored circles) in a detection task. Later memory is better for stimuli co-occurring with targets. The present experiments indicate that the ABE arises during an early phase of memory encoding that involves initial stimulus perception and comprehension rather than at a later phase entailing controlled, elaborative rehearsal. Experiment 1 demonstrated that the ABE was robust at a short study duration (700 ms) and did not increase with increasing study trial durations (1,500 ms and 4,000 ms). Furthermore, the target condition is boosted to the level of memory performance in a full-attention condition for the short duration but not the long duration. Both results followed from the early-phase account. This account also predicts that for very short study times (limiting the influence of late-phase controlled encoding and thus minimizing the usual negative effect of divided attention), the target condition will produce better memory than will the full-attention condition. Experiment 2 used a study time of 400 ms and found that words presented with targets lead to greater recognition accuracy than do either words presented with distractors or words in the full-attention condition. Consistent with the early-phase account, a divided attention condition actually produced superior memory than did the full-attention condition, a very unusual but theoretically predicted result.

Changes in body mass alone explain almost all of the variance in the serum sodium concentrations during prolonged exercise. Has commercial influence impeded scientific endeavour?

In 1991, we provided definitive evidence that exercise-associated hyponatraemia (EAH) is caused by abnormal fluid retention in those who overdrink during prolonged exercise, but this finding was ignored. Instead, in...

Protein kinase A inhibits a consolidated form of memory in Drosophila

Increasing activity of the cAMP/protein kinase A (PKA) pathway has often been proposed as an approach to improve memory in various organisms. However, here we demonstrate that single-point mutations, which decrease PKA activity, dramatically improve aversive olfactory memory in Drosophila. These mutations do not affect formation of early memory phases or of protein synthesis-dependent long-term memory but do cause a significant increase in a specific consolidated form of memory, anesthesia-resistant memory. Significantly, heterozygotes of null mutations in PKA are sufficient to cause this memory increase. Expressing a PKA transgene in the mushroom bodies, brain structures critical for memory formation in Drosophila, reduces memory back to wild-type levels. These results indicate that although PKA is critical for formation of several memory phases, it also functions to inhibit at least one memory phase.

Induction of a Specific Olfactory Memory Leads to a Long-Lasting Activation of Protein Kinase C in the Antennal Lobe of the Honeybee

In this study we investigated the role of protein kinase C (PKC) in associative learning of Apis mellifera. Changes in PKC activity induced by olfactory conditioning were measured in the antennal lobes, a brain structure involved in associative learning. Multiple conditioning trials inducing a memory different from that induced by a single conditioning trial specifically cause an increase in PKC activity. This increase begins 1 hr after conditioning, lasts up to 3 d, and is attributable to an increased level of constitutive PKC. The increased level of constitutive PKC consists of an early proteolysis-dependent phase and a late phase that requires RNA and protein synthesis. Inhibition of the pathways resulting in constitutive PKC selectively impairs distinct phases of multiple-trial induced memory. The inhibition of the proteolytic mechanism has an instant effect on an early phase of multiple-trial induced memory but does not affect acquisition and the late phase of memory. Blocking of the transient PKC activation during conditioning does not affect the induction of memory formation. Thus, the constitutive PKC in the antennal lobe seems to contribute to the early phase of memory that is induced by multiple-trial conditioning.

Memory of inhibitory avoidance in the rat is regulated by glutamate metabotropic receptors in the hippocampus.

This experiment investigated the effect on memory, in rats, of the bilateral intrahippocampal post-training infusion of the glutamate metabotropic receptor (mGLUR) agonist, ACPD (1S, 2R-aminocyclopentane dicarboxylate) and of the mGLUR antagonist, MCPG ([RS]-alpha-methyl-4-carboxyphenyl glycine). Male Wistar rats were implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus. After recovery from surgery they were trained in a step-down inhibitory avoidance task and tested for retention 24h later. Immediately or 180min after training they received a bilateral intrahippocampal infusion of saline (0.5µl), ACPD (1.0 or 2.5µg/side), MCPG (2.5µg/side) or ACPD plus MCPG, in 0.5µl saline. Upon immediate post-training infusion, ACPD caused a dose-dependent enhancement of memory and MCPG was amnestic. The effect of MCPG was antagonized by the simultaneous administration of ACPD. When given 180min after training, the drugs had no effect on memory. The results indicate that the early phase of memory is regulated by mGLURs in the hippocampus, and support the suggestion that memory involves long-term potentiation initiated at the time of training in the hippocampus.

Intrahippocampal or intraamygdala infusion of KN62, a specific inhibitor of calcium/calmodulin-dependent protein kinase II, causes retrograde amnesia in the rat

We investigated the effect of a bilateral post-training intracerebral infusion of KN62, a specific inhibitor of calcium/calmodulin-dependent protein kinase II (CaM-II), on memory. This enzyme plays a crucial role in the early phases of long-term potentiation. Male Wistar rats were implanted bilaterally with cannulae aimed at the CA1 region of the dorsal hippocampus or at the junction between the central and the basolateral nuclei of the amygdala. After recovery, rats were trained in step-down inhibitory avoidance using a 0.5-mA footshock and tested for retention 24 h later. At various times after training (0, 30, 120, or 240 min for the animals implanted into the hippocampus; 0 or 240 min for the animals implanted in the amygdala) they received, through the cannulae, an infusion of vehicle (0.1% dimethylsulfoxide in water) or KN62 (100 mumol/side). KN62 caused full retrograde amnesia when given 0 min after training into either the amygdala or the hippocampus. When given into the hippocampus 30 min post-training it had a partial amnestic effect. When given 120 min after training into the hippocampus, or 240 min after training into either structure, KN62 had no effect. The data suggest that the early phase of memory requires intact CaM-II activity in the amygdala and hippocampus and support the hypothesis that memory involves long-term potentiation initiated at the time of training in both structures.