The neurodynamic bases of imitating learning and episodic memory

In this review, three essentially important processes in the development of cognitive behavior are considered, viz., knowledge of a spatial environment by means of physical activity, coding, and the calling of the existential context of episodic memory and imitation learning based on the mirror neural mechanism. The data show that the parietal and frontal systems, which are involved in learning by imitation, allow a developing animal to obtain skills of management and motive synergies in perisomatic space, as well as to understand the intentions and the purposes of the observed actions of other individuals. At the same time the widely distributed parietal and frontal and entorhinal–hippocampal system mediates spatial knowledge and the solution of the navigation tasks that are important for the creation of the existential context of episodic memory.     

Experience-Dependent Rewiring of Specific Inhibitory Connections in Adult Neocortex

Although neocortical connectivity is remarkably stereotyped, the abundance of some wiring motifs varies greatly between cortical areas. To examine if regional wiring differences represent functional adaptations, we have used optogenetic raster stimulation to map the laminar distribution of GABAergic interneurons providing inhibition to pyramidal cells in layer 2/3 (L2/3) of adult mouse barrel cortex during sensory deprivation and recovery. Whisker trimming caused large, motif-specific changes in inhibitory synaptic connectivity: ascending inhibition from deep layers 4 and 5 was attenuated to 20%–45% of baseline, whereas inhibition from superficial layers remained stable (L2/3) or increased moderately (L1). The principal mechanism of deprivation-induced plasticity was motif-specific changes in inhibitory-to-excitatory connection probabilities; the strengths of extant connections were left unaltered. Whisker regrowth restored the original balance of inhibition from deep and superficial layers. Targeted, reversible modifications of specific inhibitory wiring motifs thus contribute to the adaptive remodeling of cortical circuits.     

Memory for events and their spatial context: models and experiments

The computational role of the hippocampus in memory has been characterized as: (i) an index to disparate neocortical storage sites; (ii) a time-limited store supporting neocortical long-term memory; and (iii) a content-addressable associative memory. These ideas are reviewed and related to several general aspects of episodic memory, including the differences between episodic, recognition and semantic memory, and whether hippocampal lesions differentially affect recent or remote memories. Some outstanding questions remain, such as: what characterizes episodic retrieval as opposed to other forms of read-out from memory; what triggers the storage of an event memory; and what are the neural mechanisms involved? To address these questions a neural-level model of the medial temporal and parietal roles in retrieval of the spatial context of an event is presented. This model combines the idea that retrieval of the rich context of real-life events is a central characteristic of episodic memory, and the idea that medial temporal allocentric representations are used in long-term storage while parietal egocentric representations are used to imagine, manipulate and re-experience the products of retrieval. The model is consistent with the known neural representation of spatial information in the brain, and provides an explanation for the involvement of Papez''s circuit in both the representation of heading direction and in the recollection of episodic information. Two experiments relating to the model are briefly described. A functional neuroimaging study of memory for the spatial context of life-like events in virtual reality provides support for the model''s functional localization. A neuropsychological experiment suggests that the hippocampus does store an allocentric representation of spatial locations.     

Interhemispheric asymmetry of neocortex and hippocampus in orienting exploratory behavior of rabbits

Correlation of discharges of cortical neurons in symmetrical points of the visual and parietal cortices and left and right hippocampal CA1 neurons was studied in freely moving rabbits during exposure to emotional stimuli. Crosscorrelation histograms were plotted. As compared to the initial state, during an active orienting exploratory reaction to stimuli, the left-side influence on right-hemispheric cortical neurons with a delay about 100 ms increased, which led to asymmetry in interhemispheric interaction with the left-side dominance. During freezing, the left-side influence became weaker, and the effects of the right hemisphere prevailed. Hippocampal asymmetry in neuronal activity was in reciprocal relationship with neocortical asymmetry. In the hippocampus, the right-side influence with a delay about 200 ms increased during the active exploratory reactions resulting in the right-side dominance. Freezing was accompanied by strengthening of the left-side influence (the left-side dominance). During the active locomotion, neuronal interaction in the hippocampus was predominantly realized in the theta-range frequency, whereas freezing was characterized by the delta-range correlation. It was concluded that the active or passive nature of a behavioral reaction to emotional stimuli was correlated with changes in asymmetry in the interhemispheric neuronal interactions at the cortical and hippocampal levels.     

Novelty-induced increased expression of immediate-early genes c-fos and arg 3.1 in the mouse brain

The detection of novel stimuli is a memory-dependent process. The presented stimulus has to be compared with memory contents to judge its novelty. In addition, the novelty of stimuli activates attention-related processes that facilitate memory formation. To determine the involvement of limbic and neocortical brain structures in novelty detection, we exposed mice to a novel gustatory stimulus (0.5% saccharin) added to their drinking fluid. We then compared the novelty-induced expression of the two immediate-early genes (IEGs) c-fos and arg 3.1, with their expression in mice familiarized with the same stimulus or mice not exposed to that stimulus. Exposure to taste novelty increased expression of c-fos and arg 3.1 mRNA in the cingulate cortex and deep layers of the parietal cortex. In addition, c-fos mRNA expression was increased in the amygdala and arg 3.1 mRNA was increased in the dentate gyrus. Expression of c-fos and arg 3.1 was elevated 30 min after the exposure to novelty. For arg 3.1, a second peak of expression was found 4.5 h after presentation of the novel stimulus. Our results indicate that the amygdala, the dentate gyrus, and the cingulate and parietal cortices may be involved in novelty detection and associated cognitive events, and suggest that c-fos and arg 3.1 play distinct roles in these processes.     

Increased attention to spatial context increases both place field stability and spatial memory

The hippocampal formation is critical for the acquisition and consolidation of memories. When recorded in freely moving animals, hippocampal pyramidal neurons fire in a location-specific manner: they are "place" cells, comprising a hippocampal representation of the animal's environment. To explore the relationship between place cells and spatial memory, we recorded from mice in several behavioral contexts. We found that long-term stability of place cell firing fields correlates with the degree of attentional demands and that successful spatial task performance was associated with stable place fields. Furthermore, conditions that maximize place field stability greatly increase orientation to novel cues. This suggests that storage and retrieval of place cells is modulated by a top-down cognitive process resembling attention and that place cells are neural correlates of spatial memory. We propose a model whereby attention provides the requisite neuromodulatation to switch short-term homosynaptic plasticity to long-term heterosynaptic plasticity, and we implicate dopamine in this process.     

Interrelated modification of excitatory and inhibitory synapses in three-layer olivary-cerebellar neural network

The model of three-layer olivary-cerebellar neural network with modifiable excitatory and inhibitory connections between diverse elements is suggested. The same Hebbian modification rules are proposed for Purkinje cells, granule (input) cells, and deep cerebellar nuclei (output) cells. The inverse calcium-dependent modification rules for these cells and hippocampal/neocortical neurones or Golgi cells are conceivably the result of the involvement of cGMP and cAMP in postsynaptic processes. The sign of simultaneous modification of excitatory and inhibitory inputs to a cell is opposite and determined by the variations in pre- and/or postsynaptic cell activity. Modification of excitatory transmission between parallel fibers and Purkinje cells, mossy fibers and granule cells, and mossy fibers and deep cerebellar nuclei cells essentially depends on inhibition effected by stellate/basket cells, Golgi cells and Purkinje cells, respectively. The character of interrelated modifications of diverse synapses in all three layers of the network is influenced by olivary cell activity. In the absence (presence) of a signal from inferior olive, the long-term potentiation (depression) in the efficacy of a synapse between input mossy fiber and output cell can be induced. The results of the suggested model are in accordance with known experimental data.     

Memory reprocessing in corticocortical and hippocampocortical neuronal ensembles.

Hippocampal cells that fire together during behaviour exhibit enhanced activity correlations during subsequent sleep, with some preservation of temporal order information. Thus, information reflecting experiences during behaviour is re-expressed in hippocampal circuits during subsequent ''offline'' periods, as postulated by some theories of memory consolidation. If the hippocampus orchestrates the reinstatement of experience-specific activity patterns in the neocortex, as also postulated by such theories, then correlation patterns both within the neocortex and between hippocampus and neocortex should also re-emerge during sleep. Ensemble recordings were made in the posterior parietal neocortex, in CA1, and simultaneously in both areas, in seven rats. Each session involved an initial sleep episode (S1), behaviour on a simple maze (M), and subsequent sleep (S2). The ensemble activity-correlation structure within and between areas during S2 resembled that of M more closely than did the correlation pattern of S1. Temporal order (i.e. the asymmetry of the cross-correlogram) was also preserved within, but not between, structures. Thus, traces of recent experience are re-expressed in both hippocampal and neocortical circuits during sleep, and the representations in the two areas tend to correspond to the same experience. The poorer preservation of temporal firing biases between neurons in the different regions may reflect the less direct synaptic coupling between regions than within them. Alternatively, it could result from a shift, between behavioural states, in the relative dominance relations in the corticohippocampal dialogue. Between-structure order will be disrupted, for example, if, during behaviour, neocortical patterns tend to drive corresponding hippocampal patterns, whereas during sleep the reverse occurs. This possibility remains to be investigated.     

The associative parietal cortex and spatial processing in rodents

It is widely acknowledged that the hippocampal formation has a central function in rodents' spatial memory and navigation. However, recent work has shown that other structures participate in specific spatial processing. That is so for the associative parietal cortex (APC). Although this neocortical region is far less developed in rodents than in humans and non-human primates, APC damage in rodents induces deficits which affect both egocentrically and allocentrically organized spatial behaviours. On the basis of behavioural (following parietal lesions) and neuroanatomical data, we propose that the APC could be at the interface between the level of perception of the physical world (egocentrically organized) and that of representations or maps (allocentrically organized) of this world. Reciprocally, the APC could also be involved in the transformation, in the opposite direction, of computations made on the basis of representations into motor actions necessary for the efficient execution of oriented behaviours within the physical world.     

Novelty‐induced increased expression of immediate‐early genes c‐fos and arg 3.1 in the mouse brain

The detection of novel stimuli is a memory‐dependent process. The presented stimulus has to be compared with memory contents to judge its novelty. In addition, the novelty of stimuli activates attention‐related processes that facilitate memory formation. To determine the involvement of limbic and neocortical brain structures in novelty detection, we exposed mice to a novel gustatory stimulus (0.5% saccharin) added to their drinking fluid. We then compared the novelty‐induced expression of the two immediate‐early genes (IEGs) c‐fos and arg 3.1, with their expression in mice familiarized with the same stimulus or mice not exposed to that stimulus. Exposure to taste novelty increased expression of c‐fos and arg 3.1 mRNA in the cingulate cortex and deep layers of the parietal cortex. In addition, c‐fos mRNA expression was increased in the amygdala and arg 3.1 mRNA was increased in the dentate gyrus. Expression of c‐fos and arg 3.1 was elevated 30 min after the exposure to novelty. For arg 3.1, a second peak of expression was found 4.5 h after presentation of the novel stimulus. Our results indicate that the amygdala, the dentate gyrus, and the cingulate and parietal cortices may be involved in novelty detection and associated cognitive events, and suggest that c‐fos and arg 3.1 play distinct roles in these processes. © 1999 John Wiley & Sons, Inc. J Neurobiol 38: 234–246, 1999     

Pattern and morphogenesis of presumptive superficial mesoderm in two closely related species, Xenopus laevis and Xenopus tropicalis

The mesoderm, comprising the tissues that come to lie entirely in the deep layer, originates in both the superficial epithelial and the deep mesenchymal layers of the early amphibian embryo. Here, we characterize the mechanisms by which the superficial component of the presumptive mesoderm ingresses into the underlying deep mesenchymal layer in Xenopus tropicalis and extend our previous findings for Xenopus laevis. Fate mapping the superficial epithelium of pregastrula stage embryos demonstrates ingression of surface cells into both paraxial and axial mesoderm (including hypochord), in similar patterns and amounts in both species. Superficial presumptive notochord lies medially, flanked by presumptive hypochord and both overlie the deep region of the presumptive notochord. These tissues are flanked laterally by superficial presumptive somitic mesoderm, the anterior tip of which also appears to overlay the presumptive deep notochord. Time-lapse recordings show that presumptive somitic and notochordal cells move out of the roof of the gastrocoel and into the deep region during neurulation, whereas hypochordal cells ingress after neurulation. Scanning electron microscopy at the stage and position where ingression occurs suggests that superficial presumptive somitic cells in X. laevis ingress into the deep region as bottle cells whereas those in X. tropicalis ingress by "relamination" (e.g., [Dev. Biol. 174 (1996) 92]). In both species, the superficially derived presumptive somitic cells come to lie in the medial region of the presumptive somites during neurulation. By the early tailbud stages, these cells lie at the horizontal myoseptum of the somites. The morphogenic pathway of these cells strongly resembles that of the primary slow muscle pioneer cells of the zebrafish. We present a revised fate map of Xenopus, and we discuss the conservation of superficial mesoderm within amphibians and across the chordates and its implications for the role of this tissue in patterning the mesoderm.     

Memory trace reactivation in hippocampal and neocortical neuronal ensembles

During active behavior, patterns of hippocampal and neocortical neuronal activity reflect ongoing inputs and their contexts. Recent neurophysiological investigations have shown that during 'off-line' periods, traces of these experiences are spontaneously reactivated in both structures. Although the functional importance of this phenomenon remains to be demonstrated, it does provide clues about the nature and mechanisms of memory retrieval and consolidation.     

Modulation of Brain Activity during a Stroop Inhibitory Task by the Kind of Cognitive Control Required

This study used a proportion congruency manipulation in the Stroop task in order to investigate, at the behavioral and brain substrate levels, the predictions derived from the Dual Mechanisms of Control (DMC) account of two distinct modes of cognitive control depending on the task context. Three experimental conditions were created that varied the proportion congruency: mostly incongruent (MI), mostly congruent (MC), and mostly neutral (MN) contexts. A reactive control strategy, which corresponds to transient interference resolution processes after conflict detection, was expected for the rare conflicting stimuli in the MC context, and a proactive strategy, characterized by a sustained task-relevant focus prior to the occurrence of conflict, was expected in the MI context. Results at the behavioral level supported the proactive/reactive distinction, with the replication of the classic proportion congruent effect (i.e., less interference and facilitation effects in the MI context). fMRI data only partially supported our predictions. Whereas reactive control for incongruent trials in the MC context engaged the expected fronto-parietal network including dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex, proactive control in the MI context was not associated with any sustained lateral prefrontal cortex activations, contrary to our hypothesis. Surprisingly, incongruent trials in the MI context elicited transient activation in common with incongruent trials in the MC context, especially in DLPFC, superior parietal lobe, and insula. This lack of sustained activity in MI is discussed in reference to the possible involvement of item-specific rather than list-wide mechanisms of control in the implementation of a high task-relevant focus.     

Hippocampal Theta Modulation of Neocortical Spike Times and Gamma Rhythm: A Biophysical Model Study

The hippocampal theta and neocortical gamma rhythms are two prominent examples of oscillatory neuronal activity. The hippocampus has often been hypothesized to influence neocortical networks by its theta rhythm, and, recently, evidence for such a direct influence has been found. We examined a possible mechanism for this influence by means of a biophysical model study using conductance-based model neurons. We found, in agreement with previous studies, that networks of fast-spiking GABA -ergic interneurons, coupled with shunting inhibition, synchronize their spike activity at a gamma frequency and are able to impose this rhythm on a network of pyramidal cells to which they are coupled. When our model was supplied with hippocampal theta-modulated input fibres, the theta rhythm biased the spike timings of both the fast-spiking and pyramidal cells. Furthermore, both the amplitude and frequency of local field potential gamma oscillations were influenced by the phase of the theta rhythm. We show that the fast-spiking cells, not pyramidal cells, are essential for this latter phenomenon, thus highlighting their crucial role in the interplay between hippocampus and neocortex.     

Dopamine and norepinephrine innervated cells in the rat prefrontal cortex: Pharmacological differentiation using microiontophoretic techniques

Biochemical and fluorescence histochemical evidence suggest dopaminergic and noradrenergic projections to the prefrontal cortex which primarily innervate the deep layers (V & VI) and superficial layers respectively. Using microiontophoretic techniques, we determined the sensitivity of cells in the rat prefrontal cortex to the inhibitory effects of dopamine (DA) and norepinephrine (NE). A clear correspondence was found between the response of a cell to DA and NE and the layer in which that cell resided. Thus cells in layers II and III were more sensitive to NE than DA, whereas the opposite was true for layers V and VI. Applied microiontophoretically, desmethylimipramine, a selective NE uptake blocker, potentiated the inhibitory effects of NE in layers II and III but not in layers V and VI. Benztropine, a DA uptake blocker, potentiated the inhibitory effects of DA only on DA sensitive cells in layers V and VI. Trifluoperazine, a DA receptor blocker, selectively blocked DA inhibition of cell activity in the deep layers. Similar experiments performed in the hippocampus and accumbens nucleus yielded results identical to those obtained for cortical layers II and III (primary NE innervation) and V and VI (primary DA innervation, respectively).These findings suggest that using microiontophoretic techniques one can pharmacologically differentiate between DA and NE innervated cells in the rat prefrontal cortex.     

Homoiogenetic Neural Inducing Activity of the Presumptive Neural Plate of Xenopus Laevis

Heteroplastic combinations were made between Xenopus laevis presumptive neural plate and competent ectoderm of Xenopus borealis . Primarily induced presumptive neural plate cells ( Xenopus laevis ) can easily be distinguished from Xenopus borealis cells by specific quinacrine fluorescence of the nuclei. It was clearly shown that presumptive neural plate, which has primarily been induced by the underlying chordamesoderm exerts homoiogenetic inducing activity on competent ectoderm. The inducing activity is increased in pieces of presumptive neural plates, when the superficial layer has been removed from the adjacent deep layers. The enhancement can be explained by the fact that the removal of the superficial layer acting as barrier allows the inducing stimulus to be easily propagated from the apical (distal) side of the deep layers of the presumptive neural plate.     

Integration and segregation of activity in entorhinal-hippocampal subregions by neocortical slow oscillations

Brain systems communicate by means of neuronal oscillations at multiple temporal and spatial scales. In anesthetized rats, we find that neocortical "slow" oscillation engages neurons in prefrontal, somatosensory, entorhinal, and subicular cortices into synchronous transitions between UP and DOWN states, with a corresponding bimodal distribution of their membrane potential. The membrane potential of hippocampal granule cells and CA3 and CA1 pyramidal cells lacked bimodality, yet it was influenced by the slow oscillation in a region-specific manner. Furthermore, in both anesthetized and naturally sleeping rats, the cortical UP states resulted in increased activity of dentate and most CA1 neurons, as well as the highest probability of ripple events. Yet, the CA3-CA1 network could self-organize into gamma bursts and occasional ripples during the DOWN state. Thus, neo/paleocortical and hippocampal networks periodically reset, self-organize, and temporally coordinate their cell assemblies via the slow oscillation.     

The intramucosal distribution of gastric alcohol dehydrogenase and aldehyde dehydrogenase activity in rats.

Using qualitative and microquantitative histo-chemical techniques, alcohol dehydrogenase and aldehyde dehydrogenase activity was studied in the gastric mucosa of male and female rats. Alcohol dehydrogenase was demonstrated by staining reactions with maximum activity in surface and neck cells and with clearly weaker activity also in parietal cells. Aldehyde dehydrogenase could be detected in surface and neck cells, and also to a comparable degree in the parietal cells. Quantitative analyses of microdissected samples yielded high values for alcohol dehydrogenase activity exclusively in the superficial part of the gastric mucosa, whereas low-Km aldehyde dehydrogenase activity showed a decreasing gradient from the surface to the deeper parts of the mucosa. Sex differences could not be confirmed.     

Histochemical and immunohistochemical profile of pink muscle fibres in some teleosts

The pink muscle of several Teleosts was examined immunohistochemically using antisera specific for the myosins of red and white muscle, and histochemically using various methods for demonstrating myosin ATPase (mATPase) activity. In the catfish the pink muscle consists of 2 different layers of fibres. The superficial layer has a low mATPase activity after both acid and alkali pre-incubation, whereas the deeper layer has a high mATPase activity after acid and alkali pre-incubation, being more resistent to these conditions even than is the white muscle. In the trout the pink muscle is composed of fibres with the same mATPase activity as in the superficial pink muscle of the catfish, whereas in the rock goby, goldfish, mullet and guppy the pink muscle is like the deep pink layer of the catfish. Immunohistochemically the fibres of the pink muscle behave like the white muscle fibres except in the guppy and rock goby in which at the level of the lateral line there occurs a transition zone between red and pink fibres. The fibres of this region react with both anti-fast and (to a lesser extent) anti-slow myosin antisera, and have a mATPase activity which, going from the superficial to the deeper fibres, gradually loses the red muscle characteristics to acquire those of the main pink muscle layer.     

Histochemical and immunohistochemical profile of pink muscle fibres in some teleosts

Summary The pink muscle of several Teleosts was examined immunohistochemically using antisera specific for the myosins of red and white muscle, and histochemically using various methods for demonstrating myosin ATPase (in ATPase) activity.In the catfish the pink muscle consists of 2 different layers of fibres. The superficial layer has a low mATPase activity after both acid and alkali pre-incubation, whereas the deeper layer has a high mATPase activity after acid and alkali pre-incubation, being more resistent to these conditions even than is the white muscle.In the trout the pink muscle is composed of fibres with the same mATPase activity as in the superficial pink muscle of the catfish, whereas in the rock goby, goldfish, mullet and guppy the pink muscle is like the deep pink layer of the catfish.Immunohistochemically the fibres of the pink muscle behave like the white muscle fibres except in the guppy and rock goby in which at the level of the lateral line there occurs a transition zone between red and pink fibres. The fibres of this region react with both anti-fast and (to a lesser extent) anti-slow myosin antisera, and have a mATPase activity which, going from the superficial to the deeper fibres, gradually loses the red muscle characteristics to acquire those of the main pink muscle layer.