Small G protein signaling in neuronal plasticity and memory formation: the specific role of ras family proteins

Small G proteins are an extensive family of proteins that bind and hydrolyze GTP. They are ubiquitous inside cells, regulating a wide range of cellular processes. Recently, many studies have examined the role of small G proteins, particularly the Ras family of G proteins, in memory formation. Once thought to be primarily involved in the transduction of a variety of extracellular signals during development, it is now clear that Ras family proteins also play critical roles in molecular processing underlying neuronal and behavioral plasticity. We here review a number of recent studies that explore how the signaling of Ras family proteins contributes to memory formation. Understanding these signaling processes is of fundamental importance both from a basic scientific perspective, with the goal of providing mechanistic insights into a critical aspect of cognitive behavior, and from a clinical perspective, with the goal of providing effective therapies for a range of disorders involving cognitive impairments.     

On the stochastic dynamics of neuronal interaction

The response of many neurons in the nervous system is a nonlinear function of membrane potential. Nevertheless, if the membrane potentials are normally distributed then their covariance satisfies a linear equation. This suggests that information in the nervous system may be processed by correlations between membrane potentials, a hypothesis which is subject to direct experimental test. The acquisition, storage, and retrieval of information in the form of correlations is consistent with present knowledge of human information processing.     

Computer-aided mapping of specific neuronal populations in the human brain

Antibody-staining methods and computer-aided microscopic systems have been used to generate high-resolution panoramic maps of specific neuronal populations in the human brain (4,6,11). This report focuses on the problems inherent in attempting high-resolution mapping of large brain sections, and describes how they are solved by computer-aided mapping. Further applications of computers to the study of brain structure are considered.     

Binocular interaction in the striatal cortex of rats during changes in intensity of a monocular stimulus

Binocular interaction was investigated by the evoked potentials method in symmetrical centers of the rat striatal cortex before and after division of the corpus callosum. One eye was always stimulated by flashes of average intensity and the other by flashes of varied intensity. Contralateral facilitation was shown to be increased with an increase in the strength of stimulation. Ipsilateral facilitation was found to exist and to change into ipsilateral depression. In all cases contralateral effects were stronger than ipsilateral. The reciprocity of contralateral and ipsilateral influences in the striatal cortex is emphasized. Division of the corpus callosum leads to strengthening of the contralateral and ipsilateral facilitatory and depressive influences. Depressive ipsilateral influences are found after callosotomy in response to weaker stimuli than before the operation.Biological Institute, Leningrad University. Translated from Neirofiziologiya, Vol. 5, No. 2, pp. 122–127, March–April, 1973.     

Binocular interaction in the parastriatal rat cortex during a change in intensity of one monocular stimulus

Binocular interaction in symmetrical centers of the parastriatal cortex in rats was investigated by the evoked potentials method before and after callosotomy. A model was used in which one eye was always stimulated by flashes of average intensity and the other by flashes of average intensity. The presence of contralateral and ipsilateral facilitation, increasing with the strength of the stimulus, was demonstrated; contralateral facilitation was more effective than ipsilateral. Synergism in the development of the contralateral and ipsilateral effects is emphasized, distinguishing them from the corresponding processes in the striatal cortex. After callosotomy the contralateral and ipsilateral facilitatory effects are intensified.Biological Institute, Leningrad University. Translated from Neirofiziologiya, Vol. 5, No. 2, pp. 128–132, March–April, 1973.     

RNA-RNA interaction is required for the formation of specific bicoid mRNA 3'' UTR-STAUFEN ribonucleoprotein particles.

The formation of the anterior pattern of the Drosophila embryo is dependent on the localization of the mRNA of the morphogen Bicoid (bcd) to the anterior pole of the egg cell. Staufen protein (STAU) is required in a late step of the localization to anchor the bcd mRNA in the anterior cytoplasm. We have shown previously that endogenous STAU associates specifically with injected bcd mRNA 3'-untranslated region (UTR), resulting in the formation of characteristic RNA-protein particles that are transported along microtubules of the mitotic spindles in a directed manner. The regions recognized by STAU in this in vivo assay are predicted to form three stem-loop structures involving large double-stranded stretches. Here, we show that the STAU interaction requires a double-stranded conformation of the stems within the RNA localization signal. In addition, base pairing between two single-stranded loops plays a major role in particle formation. This loop-loop interaction is intermolecular, not intramolecular; thus dimers or multimers of the RNA localization signal must be associated with STAU in these particles. The bcd mRNA 3' UTR can also dimerize in vitro in the absence of STAU. Thus, in addition to RNA-protein interactions, RNA-RNA interaction might be involved in the formation of ribonucleoprotein particles for transport and localization.     

Intracellular mechanisms participating in the formation of neuronal calcium signals

Ion and metabolic processes in the endoplasmic reticulum, mitochondria, plasma membrane, etc. providing calcium signaling in the cells of excitable and nonexcitable tissues are discussed.Neirofiziologiya/Neurophysiology, Vol. 36, Nos. 5/6, pp. 405–417, September–December, 2004.This revised version was published online in April 2005 with a corrected cover date and copyright year.     

Macrophage-lymphocyte interaction in the formation of delayed-type hypersensitivity

Macrophage-lymphocyte interaction was studied on 121 CBA mice during a 2-hour contact of lymph-node cells of non-immune mice with a monolayer of peritoneal macrophages of BCG-immunized mice and subsequent intravenous administration of 4.10(7) pre-incubated lymphocytes to syngenic recipients. Sensitivity to tuberculin was demonstrated in the recipients by means of blast-transformation reaction of spleen cells (stimulation index was evaluated according to incorporation of 3H-thymidine--SI = 1.32 +/- 0.40) using administration of tuberculin into the paws (Mantoux reaction--MR = 0.11 +/- 0.02 mm) and the cytotoxic effect (CTE) of the lymphocytes on tuberculin-loaded sheep-cell erythrocytes whose disintegration was assessed according to discharge of iron from the target cells (CTE = 13.98 +/- 2.73%). At transfer of intact lymphocytes after contact with non-immune macrophages, SI = 1.046 +/- 0.019; MR = 0.014 +/- 0.002 mm; CTE = 0.214 +/- 0.048%. The treatment of lymphocytes with indomethacin during the contact with macrophages induced idvere changes in the indices of delayed-type hypersensitivity (DTHS). The conclusion has been drawn that the antigen-presenting ability of macrophages can materialize in vitro.     

WNTs in synapse formation and neuronal circuitry

Wnt proteins play important roles in wiring neural circuits. Wnts regulate many aspects of neural circuit generation through their receptors and distinct signalling pathways. In this review, we discuss recent findings on the functions of Wnts in various aspects of neural circuit formation, including neuronal polarity, axon guidance, synapse formation, and synaptic plasticity in vertebrate and invertebrate nervous systems.     

Spatial and temporal stochastic interaction in neuronal assemblies

Summary The observation of various types of spatio-temporal correlations in spike-patterns of multiple cortical neurons has shifted attention from rate coding paradigms to computational processes based on the precise timing of spikes in neuronal ensembles. In the present work we develop the notion of “spatial” and “temporal interaction” which provides measures for statistical dependences in coupled stochastic processes like multiple unit spike trains. We show that the classical Willshaw network and Abeles’ synfire chain model both reveal a moderate spatial interaction, but only the synfire chain model reveals a positive temporal interaction, too. Systems that maximize temporal interaction are shown to be almost deterministic globally, but posses almost unpredictable firing behavior on the single unit level.     

Binocular interaction: contrast matching and contrast discrimination are predicted by the same model

How do signals from the 2 eyes combine and interact? Our recent work has challenged earlier schemes in which monocular contrast signals are subject to square-law transduction followed by summation across eyes and binocular gain control. Much more successful was a new 'two-stage' model in which the initial transducer was almost linear and contrast gain control occurred both pre- and post-binocular summation. Here we extend that work by: (i) exploring the two-dimensional stimulus space (defined by left- and right-eye contrasts) more thoroughly, and (ii) performing contrast discrimination and contrast matching tasks for the same stimuli. Twenty-five base-stimuli made from 1 c/deg patches of horizontal grating, were defined by the factorial combination of 5 contrasts for the left eye (0.3-32%) with five contrasts for the right eye (0.3-32%). Other than in contrast, the gratings in the two eyes were identical. In a 2IFC discrimination task, the base-stimuli were masks (pedestals), where the contrast increment was presented to one eye only. In a matching task, the base-stimuli were standards to which observers matched the contrast of either a monocular or binocular test grating. In the model, discrimination depends on the local gradient of the observer's internal contrast-response function, while matching equates the magnitude (rather than gradient) of response to the test and standard. With all model parameters fixed by previous work, the two-stage model successfully predicted both the discrimination and the matching data and was much more successful than linear or quadratic binocular summation models. These results show that performance measures and perception (contrast discrimination and contrast matching) can be understood in the same theoretical framework for binocular contrast vision.     

Spatial‐specific functions in retrograde neuronal signalling

Neurons are highly polarized cells, possessing long axons that can extend to more than 1‐m long in adult humans. In order to survive and maintain proper functions, neurons have to respond accurately in both space and time to intracellular or intercellular cues. The regulation of these comprehensive responses involves ligand‐receptor interactions, trafficking and local protein synthesis. Alterations in these mechanisms can lead to cellular dysfunction and disease. Although studies on the transport and localization of signalling endosomes along the axon have shed light on some central pathways of neuronal survival and growth as well as synapse function, little is known about the spatiotemporal mechanisms that allow the same molecule to signal differently at diverse subcellular locations and in specific neuronal populations. In this review, we will provide an overview of retrograde axonal signalling mechanisms and discuss new advances in our understanding of the spatial‐specific regulation of neuronal signalling and functions, mechanisms that allow the same signal to have a different effect in another subcellular location.