Trace feature map: a model of episodic associative memory

An approach to episodic associative memory is presented, which has several desirable properties as a human memory model. The design is based on topological feature map representation of data. An ordinary feature map is a classifier, mapping an input vector onto a topologically meaningful location on the map. A trace feature map, in addition, creates a memory trace on that location. The traces can be stored episodically in a single presentation, and retrieved with a partial cue. Nearby traces overlap, which results in plausible memory interference behavior. Performance degrades gracefully as the memory is overloaded. More recent traces are easier to recall as are traces that are unique in the memory.This research was supported in part by an ITA Foundation grant and by fellowships from the Academy of Finland, the Emil Aaltonen Foundation and the Foundation for the Advancement of Technology (Finland) when the author was at UCLA     

Circadian rhythms and memory: not so simple as cogs and gears

The influence of circadian rhythms on memory has long been studied; however, the molecular prerequisites for their interaction remain elusive. The hippocampus, which is a region of the brain important for long‐term memory formation and temporary maintenance, shows circadian rhythmicity in pathways central to the memory‐consolidation process. As neuronal plasticity is the translation of numerous inputs, illuminating the direct molecular links between circadian rhythms and memory consolidation remains a daunting task. However, the elucidation of how clock genes contribute to synaptic plasticity could provide such a link. Furthermore, the idea that memory training could actually function as a zeitgeber for hippocampal neurons is worth consideration, based on our knowledge of the entrainment of the circadian clock system. The integration of many inputs in the hippocampus affects memory consolidation at both the cellular and the systems level, leaving the molecular connections between circadian rhythmicity and memory relatively obscure but ripe for investigation.     

Plant memory: a tentative model

All memory functions have molecular bases, namely in signal reception and transduction, and in storage and recall of information. Thus, at all levels of organisation living organisms have some kind of memory. In plants one may distinguish two types. There are linear pathways from reception of signals and propagation of effectors to a type of memory that may be described by terms such as learning, habituation or priming. There is a storage and recall memory based on a complex network of elements with a high degree of integration and feedback. The most important elements envisaged are calcium waves, epigenetic modifications of DNA and histones, and regulation of timing via a biological clock. Experiments are described that document the occurrence of the two sorts of memory and which show how they can be distinguished. A schematic model of plant memory is derived as emergent from integration of the various modules. Possessing the two forms of memory supports the fitness of plants in response to environmental stimuli and stress.     

Social context hinders humans but not ravens in a short-term memory task

Using resources shared within a social group—either in a cooperative or a competitive way—requires keeping track of own and others’ actions, which, in turn, requires well-developed short-term memory. Although short-term memory has been tested in social mammal species, little is known about this capacity in highly social birds, such as ravens. We compared ravens (Corvus corax) with humans in spatial tasks based on caching, which required short-term memory of one's own and of others’ actions. Human short-term memory has been most extensively tested of all social mammal species, hence providing an informative benchmark for the ravens. A recent study on another corvid species (Corvus corone) suggests their capacity to be similar to the humans’, but short-term memory skills have, to date, not been compared in a social setting. We used spatial setups based on caches of foods or objects, divided into individual and social conditions with two different spatial arrangements of caches (in a row or a 3 × 3 matrix). In each trial, a set of three up to nine caches was presented to an individual that was thereafter allowed to retrieve all items. Humans performed better on average across trials, but their performance dropped, when they had to keep track of partner's actions. This differed in ravens, as keeping track of such actions did not impair their performance. However, both humans and ravens demonstrated more memory-related mistakes in the social than in the individual conditions. Therefore, whereas both the ravens’ and the humans’ memory suffered in the social conditions, the ravens seemed to deal better with the demands of these conditions. The social conditions had a competitive element, and one might speculate that ravens’ memory strategies are more attuned to such situations, in particular in caching contexts, than is the case for humans.     

Hysteretic behaviour of a Z-DNA-antibody complex

The amount of complex observed between Z-DNA in the supercoiled DNA from plasmid pFP332 (with d(C-G)16 cloned into pUC8) with the radiolabelled monoclonal antibody Z-D11 (with very high affinity for left-handed Z-DNA) depends on the temporal order of addition of the ligands. If the antibody is bound first a 20-30-fold higher cloroquine concentration is necessary to dissociate half of the complex compared to the case where the suprahelical density is changed first and the complex formed afterwards. This hysteretic behavior is observed for weeks and presents a kind of molecular memory system, which is based on the topological and conformational properties of DNA and the high-affinity protein binding to Z-DNA.     

Expression and purification of a recombinant avidin with a lowered isoelectric point in Pichia pastoris

A recombinant glycosylated avidin (recGAvi) with an acidic isoelectric point was expressed and secreted by the methylotrophic yeast Pichia pastoris. The coding sequence for recGAvi was de novo synthesized based on the codon usage of P. pastoris. RecGAvi is secreted at approximately 330mg/L of culture supernatant. RecGAvi monomer displays a molecular weight of 16.5kDa, as assessed by ESI mass spectrometry. N-terminal amino acid sequencing indicates the presence of three additional amino acids (E-A-E), which contribute to further lowering the isoelectric point to 5.4. The data presented here demonstrate that the P. pastoris system is suitable for the production of recGAvi and that the recombinant avidin displays biotin-binding properties similar to those of the hen-egg white protein.     

Development of a beta-galactosidase alpha-complementation system for molecular cloning in Bacillus subtilis

A versatile beta-galactosidase alpha-complementation system for Bacillus subtilis was developed, which can be used for molecular cloning in this Gram+ organism. The cloning system, which is based on the highly efficient host-vector system 6GM-pHP13, offers several advantages over previously described systems: (1) convenient direct selection of recombinants; (2) the cloning of large heterologous DNA fragments with high efficiency; and (3) the availability of six unique target sites: SphI, NdeI, NheI, BamHI, SmaI and EcoRI.     

Dynamics control of semantic processes in a hierarchical associative memory

A neural mechanism for control of dynamics and function of associative processes in a hierarchical memory system is demonstrated. For the representation and processing of abstract knowledge, the semantic declarative memory system of the human brain is considered. The dynamics control mechanism is based on the influence of neuronal adaptation on the complexity of neural network dynamics. Different dynamical modes correspond to different levels of the ultrametric structure of the hierarchical memory being invoked during an associative process. The mechanism is deterministic but may also underlie free associative thought processes. The formulation of an abstract neural network model of hierarchical associative memory utilizes a recent approach to incorporate neuronal adaptation. It includes a generalized neuronal activation function recently derived by a Hodgkin-Huxley-type model. It is shown that the extent to which a hierarchically organized memory structure is searched is controlled by the neuronal adaptability, i.e. the strength of coupling between neuronal activity and excitability. In the brain, the concentration of various neuromodulators in turn can regulate the adaptability. An autonomously controlled sequence of bifurcations, from an initial exploratory to a final retrieval phase, of an associative process is shown to result from an activity-dependent release of neuromodulators. The dynamics control mechanism may be important in the context of various disorders of the brain and may also extend the range of applications of artificial neural networks.     

An oxygen imaging system for medical applications: preliminary results.

The examination of functional processes in tissue is gaining importance in medical research. As a result the imaging and monitoring of biochemical parameters in vivo is the goal of many imaging methods. One key parameter in photodynamic therapy (PDT) is the molecular oxygen concentration. Two-dimensional monitoring of oxygen is demanded for PDT but has not yet been achieved. The use of optical methods provides a possible means of measuring molecular oxygen. The basis of this method is the measurement of the luminescence lifetime of a dye that is quenched by molecular oxygen. The molecular oxygen concentration can be monitored two-dimensionally by pixel-wise determination of the luminescence lifetime with a CCD-camera. A new O(2)-imaging system based on this principle is presented in this article. The dye Ru(bpy)(3)(2+) is quenched by molecular oxygen and was used in the first experiments with the system.     

A measurement system to detect small plant movements

A measurement system based on a photodiode array technique is presented, together with some results from recordings of phototropic responses of Avena sativa L. (cv. Seger I) coleoptiles.
A commercial photodiode array (RL-256G) was used, controlled by a likewise commercial control board RC-301. Electronic circuits were built to connect the control board to the interface card IO-801 of an Apple IIe microcomputer. The circuits constitute a fast temporary memory, which mainly contains two shift registers and two timers. Programs, which control the measurements, have been written and are presented.
Detailed recordings of blue light induced phototropic movements are presented: resolution and other features of the equipment are discussed.     

Evaluation of a model of long-term memory based on the properties of the Ca2+/calmodulin-dependent protein kinase

1.) This paper further explores the feasibility of a model for long-term memory (Lisman, 1985; Lisman and Goldring, 1988). According to this model, the value of synaptic efficacy of individual synapses is stored locally by the group of Ca2+/calmodulin-dependent protein kinase II molecules contained within the post-synaptic density. 2.) Calculations presented in a previous paper indicate that it is feasible for these kinase molecules to encode information with the stability required for long-term memory. These calculations were based on the assumption that the 30 phosphorylation sites on the enzyme are phosphorylated in a serial fashion, i.e. that the sites are not independent. This paper presents similar calculations based on the alternative assumption that the sites are phosphorylated independently. 3.) Kinase molecules that have been switched "on" undergo a continuous process of dephosphorylation and rephosphorylation. Estimates of the energy consumed by this cycle indicate that the energy required would not make unreasonable demands on neuronal metabolism. The necessity of energy consumption by molecular switches is discussed. 4.) The rate of intramolecular autophosphorylation of the Ca2+/calmodulin dependent kinase implies that the cytoplasmic free Ca2+ concentration must stay elevated for several seconds in order for kinase molecules to switch "on". How such a sustained rise in Ca2+ might be achieved is discussed. 5.) An alternative view is that long-term memory storage involves a change in gene expression. The principal evidence supporting this view is the effect of protein synthesis inhibitors on memory. A model is presented showing that the observed effect of protein synthesis inhibitors does not necessarily imply that information storage is at the level of gene expression. 6.) The distinction between "presynaptic" and "postsynaptic" associative learning mechanisms is discussed. It is concluded that this distinction can be misleading and that the possibility that the underlying mechanisms are similar should not be excluded.     

Structural and molecular origin of information recording/reading

On the basis of experimental data on the thermoinduced state of water dispersions of natural and synthetic phospholipids in the presence of nootropic agents, a new phenomenological molecular mechanism of information recording/reading was proposed. The mechanism is based on the polymorphism of membrane lipids. A new approach, to the problem of memory was suggested, which considers memory as an information data bank and separates this concept from the concept of the mechanisms of information recording/reading.     

Dynamics control of semantic processes in a hierarchical associative memory

 A neural mechanism for control of dynamics and function of associative processes in a hierarchical memory system is demonstrated. For the representation and processing of abstract knowledge, the semantic declarative memory system of the human brain is considered. The dynamics control mechanism is based on the influence of neuronal adaptation on the complexity of neural network dynamics. Different dynamical modes correspond to different levels of the ultrametric structure of the hierarchical memory being invoked during an associative process. The mechanism is deterministic but may also underlie free associative thought processes. The formulation of an abstract neural network model of hierarchical associative memory utilizes a recent approach to incorporate neuronal adaptation. It includes a generalized neuronal activation function recently derived by a Hodgkin-Huxley-type model. It is shown that the extent to which a hierarchically organized memory structure is searched is controlled by the neuronal adaptability, i.e. the strength of coupling between neuronal activity and excitability. In the brain, the concentration of various neuromodulators in turn can regulate the adaptability. An autonomously controlled sequence of bifurcations, from an initial exploratory to a final retrieval phase, of an associative process is shown to result from an activity-dependent release of neuromodulators. The dynamics control mechanism may be important in the context of various disorders of the brain and may also extend the range of applications of artificial neural networks. Received: 19 April 1995/Accepted in revised form: 8 August 1995     

The search for a hippocampal engram

Understanding the molecular and cellular changes that underlie memory, the engram, requires the identification, isolation and manipulation of the neurons involved. This presents a major difficulty for complex forms of memory, for example hippocampus-dependent declarative memory, where the participating neurons are likely to be sparse, anatomically distributed and unique to each individual brain and learning event. In this paper, I discuss several new approaches to this problem. In vivo calcium imaging techniques provide a means of assessing the activity patterns of large numbers of neurons over long periods of time with precise anatomical identification. This provides important insight into how the brain represents complex information and how this is altered with learning. The development of techniques for the genetic modification of neural ensembles based on their natural, sensory-evoked, activity along with optogenetics allows direct tests of the coding function of these ensembles. These approaches provide a new methodological framework in which to examine the mechanisms of complex forms of learning at the level of the neurons involved in a specific memory.     

A neuron model as an universal element of self-learning networks for pattern recognition

A mathematical model of the neuron, socalled D-neuron, is proposed on the basis of some new conceptions concerning the molecular mechanism of the synaptical memory. According to these conceptions, the receptors of the neuron reception surface are divided into functional independent fields of receptors. The receptors of any field belong to corresponding membrane protein complex which contains moreover Na⁺-channels, K⁺-channels and eventually other protein subunits. Three processes are supposed to take place in any complex by its interaction with chemical transmitters: i cooperative transitions of the subunits, ii time-controlled transport of ions and iii changes of concentrations of the protein complex subunits. These processes correspond to the following information processings: i recording in the memory, ii discrimination and iii accomodation. In this paper they all are described by an idealized system of algebraic and differential equations. The proposed neuron model can account for the short- and long-term memory mechanism on the level of a single neuron as well as for the control of the neuron networks by the hormones. finally, the neuron model is presented as a universal unit of self-learning networks.     

Epigenetic regulation of learning and memory by Drosophila EHMT/G9a

The epigenetic modification of chromatin structure and its effect on complex neuronal processes like learning and memory is an emerging field in neuroscience. However, little is known about the "writers" of the neuronal epigenome and how they lay down the basis for proper cognition. Here, we have dissected the neuronal function of the Drosophila euchromatin histone methyltransferase (EHMT), a member of a conserved protein family that methylates histone 3 at lysine 9 (H3K9). EHMT is widely expressed in the nervous system and other tissues, yet EHMT mutant flies are viable. Neurodevelopmental and behavioral analyses identified EHMT as a regulator of peripheral dendrite development, larval locomotor behavior, non-associative learning, and courtship memory. The requirement for EHMT in memory was mapped to 7B-Gal4 positive cells, which are, in adult brains, predominantly mushroom body neurons. Moreover, memory was restored by EHMT re-expression during adulthood, indicating that cognitive defects are reversible in EHMT mutants. To uncover the underlying molecular mechanisms, we generated genome-wide H3K9 dimethylation profiles by ChIP-seq. Loss of H3K9 dimethylation in EHMT mutants occurs at 5% of the euchromatic genome and is enriched at the 5' and 3' ends of distinct classes of genes that control neuronal and behavioral processes that are corrupted in EHMT mutants. Our study identifies Drosophila EHMT as a key regulator of cognition that orchestrates an epigenetic program featuring classic learning and memory genes. Our findings are relevant to the pathophysiological mechanisms underlying Kleefstra Syndrome, a severe form of intellectual disability caused by mutations in human EHMT1, and have potential therapeutic implications. Our work thus provides novel insights into the epigenetic control of cognition in health and disease.     

An algebraic model of an associative noise-like coding memory

A mathematical model of an associative memory is presented, sharing with the optical holography memory systems the properties which establish an analogy with biological memory. This memory system-developed from Gabor's model of memoryis based on a noise-like coding of the information by which it realizes a distributed, damage-tolerant, equipotential storage through simultaneous state changes of discrete substratum elements. Each two associated items being stored are coded by each other by means of two noise-like patterns obtained from them through a randomizing preprocessing. The algebraic braic transformations operating the information storage and retrieval are matrix-vector products involving Toeplitz type matrices. Several noise-like coded memory traces are superimposed on a common substratum without crosstalk interference; moreover, extraneous noise added to these memory traces does not injure the stored information. The main performances shown by this memory model are: i) the selective, complete recovering of stored information from incomplete keys, both mixed with extraneous information and translated from the position learnt; ii) a dynamic recollection where the information just recovered acts as a new key for a sequential retrieval process; iii) context-dependent responses. The hypothesis that the information is stored in the nervous system through a noise-like coding is suggested. The model has been simulated on a digital computer using bidimensional images.     

The persistence of long-term memory: a molecular approach to self-sustaining changes in learning-induced synaptic growth

Recent cellular and molecular studies of both implicit and explicit memory storage suggest that experience-dependent modulation of synaptic strength and structure is a fundamental mechanism by which these diverse forms of memory are encoded and stored. For both forms of memory storage, some type of synaptic growth is thought to represent the stable cellular change that maintains the long-term process. In this review, we discuss recent findings on the molecular events that underlie learning-related synaptic growth in Aplysia and discuss the possibility that an active, prion-based mechanism is important for the maintenance of the structural change and for the persistence of long-term memory.