Multiple memory mechanisms in the cerebellum?

Long-term potentiation (LTP) and long-term depression (LTD) are arguably two of the most widely discussed cellular plasticity mechanisms for learning and memory. However, the extent to which they are required for behavioral plasticity and learning is not clear. In this issue of Neuron, Boyden et al. use mice lacking CaMKIV and Hansel et al. use mice lacking alphaCaMKII to assess the contribution of LTD to cerebellar learning.     

Age-related memory impairment. Is the cure worse than the disease?

Aging impairs multiple memory systems. The neurochemical substrates of normal memory differ between memory systems. In this issue of Neuron, Ramos et al. find that activation of protein kinase A, which has been reported to improve hippocampal-dependent spatial memory in aged animals, has the opposite effect on prefrontal cortex-dependent working memory in aged animals.     

Can the theory of critical distances predict the failure of shape memory alloys?

Components made from shape memory alloys (SMAs) such as nitinol often fail from stress concentrations and defects such as notches and cracks. It is shown here for the first time that these failures can be predicted using the theory of critical distances (TCDs), a method which has previously been used to study fracture and fatigue in other materials. The TCD uses the stress at a certain distance ahead of the notch to predict the failure of the material due to the stress concentration. The critical distance is believed to be a material property which is related to the microstructure of the material. The TCD is simply applied to a linear model of the material without the need to model the complication of its non-linear behaviour. The non-linear behaviour of the material at fracture is represented in the critical stress. The effect of notches and short cracks on the fracture of SMA NiTi was studied by analysing experimental data from the literature. Using a finite element model with elastic material behaviour, it is shown that the TCD can predict the effect of crack length and notch geometry on the critical stress and stress intensity for fracture, with prediction errors of less than 5%. The value of the critical distance obtained for this material was L?=?90?μm; this may be related to its grain size. The effects of short cracks on stress intensity were studied. It was shown that the same value of the critical distance (L?=?90?μm) could estimate the experimental data for both notches and short cracks.     

Recognition memory: what are the roles of the perirhinal cortex and hippocampus?

The hallmark of medial temporal lobe amnesia is a loss of episodic memory such that patients fail to remember new events that are set in an autobiographical context (an episode). A further symptom is a loss of recognition memory. The relationship between these two features has recently become contentious. Here, we focus on the central issue in this dispute--the relative contributions of the hippocampus and the perirhinal cortex to recognition memory. A resolution is vital not only for uncovering the neural substrates of these key aspects of memory, but also for understanding the processes disrupted in medial temporal lobe amnesia and the validity of animal models of this syndrome.     

Cellular processes in the amygdala: gates to emotional memory?

The amygdala is considered a core structure of the so-called limbic system and has been implicated in a variety of functions, including emotional interpretation of sensory information, emotional arousal, emotional memory, fear and anxiety, and related clinical disorders. Despite the clinical and functional importance of the amygdala, it is only recently that some general principles of intra-amygdaloid mechanisms of signal processing that are relevant for fear behavior and memory have emerged from behavioral, anatomical, electrophysiological, and neurochemical studies performed in the amygdala of various mammalian species in vivo, in situ and in vitro.     

Is cholinergic activity of the caudate nucleus involved in memory?

A review was made of experiments dealing with the involvement of cholinergic activity of the caudate nucleus in memory processes. Injections of acetylcholine-receptor blockers or of neurotoxins against cholinergic interneurons into the striatum produce marked impairments in acquisition and retention of instrumental tasks while injections of acetylcholine or choline into the caudate produce the opposite effect. However, after a period of overtraining cholinergic blockade or interference with neural activity of the caudate does not produce significant deficits in retention. It is concluded that striatal cholinergic activity is critically involved in memory of recent events and that long-term memory is mediated by different neurochemical systems outside the caudate nucleus.     

Facilitation of memory retrieval by the “anti-addictive” alkaloid,ibogaine

Anecdotal observations in humans indicate that indole alkaloid ibogaine may have antiaddictive properties. It has been suggested that the therapeutic action of ibogaine may depend upon facilitated access to the past experiences, purportedly influencing the initiation of drug addiction. To determine if ibogaine may facilitate memory retrieval, rats were trained in the Morris maze spatial navigation task. It has been found that ibogaine (0.25 or 2.5 mg/kg) or O-desmethyl-ibogaine (2.5 mg/kg) but not t-Butyl ibogaine, administered just before the test trial, facilitated spatial memory retrieval compared to rats receiving placebo treatment. It is concluded that although previously described NMDA receptor antagonistic properties of ibogaine may represent a locus for at least some of its actions, other mechanisms, involving facilitation of memory retrieval may be of importance for its anti-addictive effects.     

To the memory of Georgy Viktorovich Lopashov (1912–2010)

Losses of Science

To the memory of Georgy Viktorovich Lopashov (1912–2010)     

Drosophila memory: will Orb(2) predict the future?

Genetically tractable organisms with relatively simple nervous systems offer a realistic platform to understand how and where memories are formed and stored in defined neural circuits. Recent work in Drosophila provides promise that this analysis may soon reach the resolution of identifiable synapses.     

Samuel Butler and human long term memory: Is the cupboard bare?

Memory studies in biological systems distinguish three informational processes that are generally sequential—production/acquisition, storage, and retrieval/use. Identification of DNA as a storage form for hereditary information accelerated progress in that field. Assuming the path of successful elucidation in one memory field (heredity) to be heuristic for elucidation in another (brain), then progress in neuroscience should accelerate when a storage form is identified. In the 19th century Ewald Hering and Samuel Butler held that heredity and brain memory both involved the storage of information and that the two forms of storage were the same. Hering specified storage as ‘molecular vibrations’ but, while making a fuller case, Butler was less committal. In the 20th century, the ablation studies of Karl Lashley failed to identify unique sites for storage of brain information, and Donald Hebb's ‘synaptic plasticity’ hypothesis of distributed storage over a neuronal network won favor. In the 21st century this has come under attack, and the idea that brain and hereditary information are stored as DNA is advocated. Thus, albeit without attribution, Butler's idea is reinstated. Yet, while the case is still open, the synaptic plasticity and DNA hypotheses have problems. Two broad alternatives remain on the table. Long term memory is located: (1) in the brain, either in some other macromolecular form (e.g. protein, lipid) or in some sub-molecular form (e.g. quantum computing and ‘brain as holograph’ hypotheses) or (2) outside the brain. The suggestion of the medieval physician Avicenna that the brain ‘cupboard’ is bare—i.e. the brain is a perceptual, not storage, organ—is consistent with a mysterious ‘universe as holograph’ model. Understanding how Butler came to contribute could be heuristic for future progress in a field fraught with ‘fractionation and disunity’.     

Development of the brain’s organization of working memory in young schoolchildren

In 7–8 and 9–10-years old children, we studied event-related potentials (ERPs) during paired comparison of non-verbalizable visuospatial stimuli presented at an interval of 1.5–1.8 s. Age-related differences were found in the involvement of various cortical areas in the formation and retention of a short-term memory trace of the reference stimulus and during comparison of the short-term trace with the test stimulus presented. In both age groups, working memory was associated with an elevation of the amplitude of the sensory-specific N1 component in the visual cortical areas. Age-related differences in the processing of sensory-specific characteristics of a stimulus were the greatest in the ERPs to the test stimulus: at the age of 9–10, the N1 component amplitude was significantly increased in all caudal leads and, in the occipital and inferior temporal leads, this component was preceded by P1 component. At this age, we observed the early involvement of the inferior frontal cortex, which was not observed at the age of seven. The increase in positivity over that area was observed in the interval of 100–200 ms. Substantial differences between age groups were found in the late ERP component corresponding to cognitive processes. At the age of 7–8, the presentation of both the reference and test stimuli causes the increase in the amplitude of the slow positive complex (SPC) in the caudal liads with the maximum enhancement found in the interval of 300–800 ms in the parietal leads. At the age of 9–10, the SPC increase, much like in adults, was observed in ERP to the test stimulus only. At this age, adult-like specific changes in the late phases of ERPs were observed in the fronto-central regions at the different stages of working memory. They are the increases in the negative N400 wave in the ERP to the reference stimulus and the SPC to the test stimulus. These data show that, at the age of 9–10, the functional organization of working memory of the adult type is formed; however, the extent to which the frontal cortex, and its dorsal regions in particular, is involved into working memory processes does not meet yet a definitive level.     

Estrogen and memory in women: how can we reconcile the findings?

Although several randomized controlled trials (RCTS) of surgically menopausal women have provided evidence that estrogen protects aspects of memory, many cross-sectional and longitudinal studies, including those from the RCT, the Women's Health Initiative Memory Study (WHIMS), have reported inconsistent information with regard to the relationship between estrogen and aspects of cognitive function. Although numerous reasons could be offered to explain these discrepancies in research findings, recent evidence from rodent, nonhuman primate, and human studies consistently suggests that one possibility may be critical to our understanding of the estrogenic effect on memory. Results of these animal and human studies indicate that the initiation of estrogen treatment at the time of menopause, or soon after ovariectomy (OVX), provides a window of opportunity for the preservation of memory in females whereas the administration of the hormone following a considerable delay in time after OVX has little or no beneficial effect on cognition. Considering the evidence that, in several organ systems, heightened disease risks accrue to a longer duration of estrogen deprivation in women, it would seem important to determine whether this is also true for brain structure and function in order to protect the quality of life for the considerable number of women who undergo a surgical menopause before their natural menopause had occurred.     

Glycogen synthase kinase 3β in the basolateral amygdala is critical for the reconsolidation of cocaine reward memory

Exposure to cocaine-associated conditioned stimuli elicits craving and increases the probability of cocaine relapse in cocaine users even after extended periods of abstinence. Recent evidence indicates that cocaine seeking can be inhibited by disrupting the reconsolidation of the cocaine cue memories and that basolateral amygdala (BLA) neuronal activity plays a role in this effect. Previous studies demonstrated that glycogen synthase kinase 3β (GSK-3β) plays a role in the reconsolidation of fear memory. Here, we used a conditioned place preference procedure to examine the role of GSK-3β in the BLA in the reconsolidation of cocaine cue memories. GSK-3β activity in the BLA, but not central amygdala (CeA), in rats that acquired cocaine (10 mg/kg)-induced conditioned place preference increased after re-exposure to a previously cocaine-paired chamber (i.e., a memory reactivation procedure). Systemic injections of the GSK-3β inhibitor lithium chloride after memory reactivation impaired the reconsolidation of cocaine cue memories and inhibited subsequent cue-induced GSK-3β activity in the BLA. Basolateral amygdala, but not central amygdala, injections of SB216763, a selective inhibitor of GSK-3β, immediately after the reactivation of cocaine cue memories also disrupted cocaine cue memory reconsolidation and prevented cue-induced increases in GSK-3β activity in the BLA. The effect of SB216763 on the reconsolidation of cocaine cue memories lasted at least 2 weeks and was not recovered by a cocaine priming injection. These results indicate that GSK-3β activity in the BLA mediates the reconsolidation of cocaine cue memories.     

Problems of learning and memory: one or multiple memory systems?

Learning, and hence memory, is ubiquitous not only throughout the animal kingdom, but apparently throughout many regions of the brain. Is all learning reducible to a single common form? Neuropsychological dissociations suggest that the mammalian brain possesses a number of different and potentially independent memory systems, with different mechanisms and anatomical dispositions, some of which are neurally widely dispersed and others of which are narrowly organized. Among the types considered are: (i) short-term memory; (ii) knowledge and skills; (iii) stable associative memory; (iv) event memory; and (v) priming. As double or multiple dissociations do not lead to logically inevitable conclusions, it has been argued that an alternative to multiple memory systems is variable modes of processing. But these, too, would be dissociable on the same lines of evidence. Dissociations, if strong and absolute, have strong pragmatic power when they are combined with evolutionary and neuroscientific evidence. Multiple memory systems may possibly share some common cellular mechanisms, but such mechanisms do not define the separate properties at the systems level.     

Rarity,ecological memory,rate of floral change in phytoplankton—and the mystery of the Red Cock

In this article, we attempt to estimate the contemporary phytoplankton species pool of a particular lake, by assessing the rate of floral change over a period of 15 years. Phytoplankton time series data from Lake Stechlin, an oligo-mesotrophic lake in the Baltic Lake District (Germany) were used. Of the 254 algal species recorded during the 15-year of studies with roughly biweekly sampling, 212 species were planktonic. In the individual plankton years, the recorded total number of species changed between 97 and 122, of which the number of dominants (>1% contribution to the annual average of total biomass) was only 10–19. The 15-year cumulative number of species exhibited an almost linear increase after an initial saturation phase. This increase was attributed to two reasons: increase of sample size and immigration of species new to the flora. Based on a probabilistic model developed in this study, we estimated the number of co-existing planktonic species of the lake as some 180, and the rate of floral change as 1–2 species per year. Of these co-existing species, only few maintain the matter–energy processing ecosystem functions in any particular plankton year. Selection of these dominants is probably driven by mesoclimatic cycles, coupled with human-induced forcing, like eutrophication. All others are hiding as an ecological memory, in the sense of the capacity or experiences of past states to influence present or future responses of the community. Data analyses suggest that selection of the ‘memory species’ that show temporary abundance increases over shorter (several years) periods are largely dependent upon the dominants. These results show that interspecific interactions and the particular autecological features of the dominants, together with their effects on the whole ecosystem, act as a major organizing force. Some phytoplankton species, like Planktothrix rubescens, are efficient ecosystem engineers with cascading effects of both a top-down and bottom-up nature. Historical scientific data on Planktothrix blooms in Lake Stechlin suggest cyclic patterns in long-term development of phytoplankton which, as the legend of the Red Cock suggests, dates back much further than scientific archives.