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PubMed1998

Mapping episodic memory.

This paper presents an analysis of brain regions generally associated with a frequently used episodic memory task; visual word recognition. The results from five positron emission tomography studies of regional cerebral blood flow, involving a total of nine pairwise comparisons of brain activity related to episodic retrieval and to performance on non-episodic reference tasks, were considered. Across studies, increased activity has been observed in the right anterior and posterior prefrontal, anterior cingulate, bilateral parietal, and cerebellar regions. Decreased activity has been found in bilateral temporal and left midfrontal regions. Comparison of this activation pattern with those of other memory tasks, episodic and semantic, indicate that the right anterior and posterior prefrontal regions guide processes selectively demanded by episodic memory retrieval. There is suggestive evidence from subtraction analyses that these prefrontal regions are activated by different processing components, and analyses of functional connectivity provide further support for functional differentiation. These analyses also point to a critical role of medial-temporal brain regions in episodic retrieval. Taken together, these results show that episodic memory retrieval is mediated by an extensive set of brain regions, some of which seem to be specifically engaged by episodic remembering.

Animals↗
PubMed2003

Spinal dorsal horn cell receptive field size is increased in adult rats following neonatal hindpaw skin injury.

Local tissue damage in newborn rats can lead to changes in skin sensitivity that last into adulthood and this is likely to be due to plasticity of developing peripheral and central sensory connections. This study examines the functional connections of dorsal horn neurons in young and adult rats that have undergone local skin damage at birth. Newborn rat pups were halothane anaesthetised and received either a unilateral subcutaneous plantar injection of 1 % lambda-carrageenan or a unilateral plantar foot injury made by removal of 2 mm x 2 mm of skin. At 3 weeks, (postnatal day (P) 19-23) and 6 weeks (P40-44) in vivo extracellular recordings of single dorsal horn cells with plantar cutaneous receptive fields were made under urethane anaesthesia (2 g kg-1) and responses to mechanical and electrical stimulation of the skin were assessed. Following neonatal carrageenan inflammation, dorsal horn neuron properties and receptive field sizes at 3 weeks were the same as those of controls. In contrast, following neonatal skin injury, dorsal horn cell receptive field sizes were significantly greater than those of controls at 3 weeks (2.5-fold) and at 6 weeks (2.2-fold). Mechanical thresholds, mechanical response magnitudes and evoked responses to single and repeated A and C fibre stimulation remained unaffected. These results show that early skin injury can cause prolonged changes in central sensory connections that persist into adult life, long after the skin has healed. Enlarged dorsal horn neuron receptive field sizes provide a physiological mechanism for the persistent behavioural hypersensitivity that follows neonatal skin injury in rats and for the prolonged sensory changes reported in human infants after early pain and injury.

Animals↗
PubMedDate not supplied

Cell-assembly coding in several memory processes.

The present paper discusses why the cell assembly, i.e., an ensemble population of neurons with flexible functional connections, is a tenable view of the basic code for information processes in the brain. The main properties indicating the reality of cell-assembly coding are neurons overlaps among different assemblies and connection dynamics within and among the assemblies. The former can be detected as multiple functions of individual neurons in processing different kinds of information. Individual neurons appear to be involved in multiple information processes. The latter can be detected as changes of functional synaptic connections in processing different kinds of information. Correlations of activity among some of the recorded neurons appear to change in multiple information processes. Recent experiments have compared several different memory processes (tasks) and detected these two main properties, indicating cell-assembly coding of memory in the working brain. The first experiment compared different types of processing of identical stimuli, i.e., working memory and reference memory of auditory stimuli. The second experiment compared identical processes of different types of stimuli, i.e., discriminations of simple auditory, simple visual, and configural auditory-visual stimuli. The third experiment compared identical processes of different types of stimuli with or without temporal processing of stimuli, i.e., discriminations of elemental auditory, configural auditory-visual, and sequential auditory-visual stimuli. Some possible features of the cell-assembly coding, especially "dual coding" by individual neurons and cell assemblies, are discussed for future experimental approaches.

Animals↗
PubMed2002

Theoretical neuroanatomy and the connectivity of the cerebral cortex.

Over recent years, a wealth of neuroanatomical information on the pattern of interconnections between segregated areas of the cerebral cortex has become available. Here, we describe a set of structural measures, based on graph theory, which can be used to analyze these anatomical patterns. We describe relationships between these structural measures and measures based on patterns of functional connectivity, i.e. patterns of correlations in neural activity. We find that networks capable of producing highly complex functional dynamics share common structural motifs. These motifs are also found in cortical connection matrices, which are characterized by the existence of densely linked groups of areas, low potential wiring length, and a high abundance of reciprocal connections and short cycles. An analysis of cortical functional connectivity demonstrates the existence of functional clusters of highly interactive areas, producing highly complex dynamics. The combined structural and functional analysis outlined in this chapter provides insight into the large-scale functional organization of distributed cortical systems.

Animals↗
PubMed2026

Continuous theta-burst stimulation over the right DLPFC modulates central executive network connectivity in depression: exploratory analysis of a randomized clinical trial.

Previous studies suggest that transcranial magnetic stimulation exerts antidepressant effects and is associated with alterations in functional connectivity (FC), but the neural correlates remain unclear. This exploratory sham-controlled trial investigated the effect of continuous theta-burst stimulation (cTBS) over the right dorsolateral prefrontal cortex (DLPFC) on FC in major depressive disorder (MDD). Seventy MDD patients were randomized to receive two-week treatment of personalized cTBS or sham stimulation. Resting-state fMRI was performed at baseline and post-treatment. Ultimately, 31 patients in the active cTBS group and 28 patients in the sham group passed imaging quality control and were included in the final analysis. To identify the FC that may have been influenced by cTBS treatment, two complementary FC analyses were conducted: (1) voxel-wise degree centrality (DC) followed by seed-based FC, and (2) an individual FC analysis based on the stimulation targets. Furthermore, correlations between FC changes and clinical symptoms improvement were examined. Both groups exhibited reductions of depression scores, with greater improvement in the active group. Compared to the sham group, active cTBS showed increased DC in the precuneus and elevated FC between the precuneus (within the para-cingulate network) and the right inferior parietal lobule (IPL) and DLPFC. Further stimulation target-based analysis revealed increased FC between stimulation targets and both the precuneus and visual regions following treatment. Our findings reveal neural changes associated with cTBS over the right DLPFC in MDD, notably involving the precuneus and its connectivity with the right IPL/DLPFC, suggesting alterations within the central executive network. TRIAL REGISTRATION: chictr.org.cn; ChiCTR2300068273.

Humans↗
PubMed2004

Parietal cortex and representation of the mental Self.

For a coherent and meaningful life, conscious self-representation is mandatory. Such explicit "autonoetic consciousness" is thought to emerge by retrieval of memory of personally experienced events ("episodic memory"). During episodic retrieval, functional imaging studies consistently show differential activity in medial prefrontal and medial parietal cortices. With positron-emission tomography, we here show that these medial regions are functionally connected and interact with lateral regions that are activated according to the degree of self-reference. During retrieval of previous judgments of Oneself, Best Friend, and the Danish Queen, activation increased in the left lateral temporal cortex and decreased in the right inferior parietal region with decreasing self-reference. Functionally, the former region was preferentially connected to medial prefrontal cortex, the latter to medial parietal. The medial parietal region may, then, be conceived of as a nodal structure in self-representation, functionally connected to both the right parietal and the medial prefrontal cortices. To determine whether medial parietal cortex in this network is essential for episodic memory retrieval with self-representation, we used transcranial magnetic stimulation over the region to transiently disturb neuronal circuitry. There was a decrease in the efficiency of retrieval of previous judgment of mental Self compared with retrieval of judgment of Other with transcranial magnetic stimulation at a latency of 160 ms, confirming the hypothesis. This network is strikingly similar to the network of the resting conscious state, suggesting that self-monitoring is a core function in resting consciousness.

Adult↗
PubMed1994

Changes in the male rat hepatic cytochrome P-450 level, heme oxygenase and delta-aminolevulinic acid synthase activities at various stages of life.

delta-Aminolevulinic acid synthase and heme oxygenase are closely functionally connected with the hepatic microsomal mixed function oxydase system. There is a wide range of changes in microsomal heme oxygenase activity, cytochrome P-450 level and mitochondrial delta-aminolevulinic acid synthase activity in rat livers at various stages of life. We tried to investigate the spontaneous phases of these enzymatic protein activities and the levels of cytochrome P-450 as a function of age. We noted that each of these proteins change their activity and level very characteristically during the rats' lifetime. However, correlations between heme oxygenase activity, delta-aminolevulinic acid synthase activity and cytochrome P-450 levels still need to be investigated to elucidate the mechanism of these connections.

5-Aminolevulinate Synthetase↗
PubMed1985

Interactions between rostral pontine and ventral medullary respiratory neurons.

Lesioning studies have demonstrated that the respiratory rhythm is generated within the brain stem and that connections between the pons and the medulla must be intact for the generation of eupneic breathing in the decerebrate or anesthetized vagotomized cat. However, the nature of proposed functional connections between pontine and medullary respiratory neurons is not well understood. The possibility of interactions between respiratory neurons of the rostral pons (n. parabrachialis medialis, Kölliker-Fuse nucleus) and the ipsilateral ventral respiratory group (VRG; n. retroambigualis, n. ambiguus, retrofacial nucleus) was investigated because of neuroanatomical and electrophysiological evidence for such connections. Phrenic nerve activity and pontine and medullary single-unit respiratory related activities were recorded extracellularly in 44 decerebrate, vagotomized, paralyzed, and artificially ventilated cats. Cross-correlation analysis was employed to detect and evaluate functional associations of pairs of cells. Eighteen (7%) of the 255 pairs of respiratory neurons analyzed showed evidence of short time scale correlations indicative of a functional interaction. The interpretations of the detected correlations suggest that some cell pairs were correlated due to mono- or paucisynaptic connections, while others were correlated due to the influence of an unobserved shared input. The interpretations for 11 of the 15 cell pairs for which a monosynaptic connection may be postulated involve a projection from a tonically active respiratory neuron. Twelve of the 18 positive correlations involved neurons whose maximum rates of discharge occurred during different parts of the respiratory cycle. The results of this study provide the first evidence of functional connections among pontine and medullary respiratory neurons based on the evaluation of simultaneously recorded spike trains and suggest that the role of the rostral pontine respiratory neurons in the control of the respiratory rhythm may be mediated by various types of interactions. When considered with the results of other studies, our data suggest that monosynaptic interactions between VRG and rostral pontine respiratory neurons play a limited role in the control of the respiratory cycle in the decerebrate vagotomized cat. It is likely that the influence of the pons on ventral medullary neurons (and vice-versa) is also exerted via polysynaptic pathways and/or via brain stem neurons not sampled in this study.

Animals↗
PubMed1999

Specificity of color connectivity between primate V1 and V2.

To examine the functional interactions between the color and form pathways in the primate visual cortex, we have examined the functional connectivity between pairs of color oriented and nonoriented V1 and V2 neurons in Macaque monkeys. Optical imaging maps for color selectivity, orientation preference, and ocular dominance were used to identify specific functional compartments within V1 and V2 (blobs and thin stripes). These sites then were targeted with multiple electrodes, single neurons isolated, and their receptive fields characterized for orientation selectivity and color selectivity. Functional interactions between pairs of V1 and V2 neurons were inferred by cross-correlation analysis of spike firing. Three types of color interactions were studied: nonoriented V1/nonoriented V2 cell pairs, nonoriented V1/oriented V2 cell pairs, and oriented V1/nonoriented V2 cell pairs. In general, interactions between V1 and V2 neurons are highly dependent on color matching. Different cell pairs exhibited differing dependencies on spatial overlap. Interactions between nonoriented color cells in V1 and V2 are dependent on color matching but not on receptive field overlap, suggesting a role for these interactions in coding of color surfaces. In contrast, interactions between nonoriented V1 and oriented V2 color cells exhibit a strong dependency on receptive field overlap, suggesting a separate pathway for processing of color contour information. Yet another pattern of connectivity was observed between oriented V1 and nonoriented V2 cells; these cells exhibited interactions only when receptive fields were far apart and failed to interact when spatially overlapped. Such interactions may underlie the induction of color and brightness percepts from border contrasts. Our findings thus suggest the presence of separate color pathways between V1 and V2, each with differing patterns of convergence and divergence and distinct roles in color and form vision.

Animals↗
PubMedDate not supplied

[The connection of adrenal function to nutritional factors and milk productivity in ruminant animals].

In this paper the literature and experimental data about ruminant's adrenal function in the connect with feeding level, ration structure and lactation are generalized and systematized. It is shown, that the adrenal secretion and either glucocorticoid, or katecholamine metabolism can be changed in the dependence on the alimentary factors. When the animals feeding is not adequate physiologically, increased cortisol secretion is necessary for supporting of glucose level in the normal value, what leads to increased loading to the adrenal cortex and is accompanied by redistribution of this hormone between plasma and erythrocytes. The hypothesis explaining the received results is advanced. The ability of the endocrine indexes utilization for the estimation of physiological adequately of rations is discussed. The role of adrenal hormones in the regulation of the mammary gland supplying with the milk precursors, and the mechanisms of these hormones action (either positive, or negative) to the organism lactation function are studying.

Adrenal Glands↗
PubMed2002

Gap junction proteins expressed during development are required for adult neural function in the Drosophila optic lamina.

We provide evidence that gap junction proteins, expressed during development, are necessary for the formation of normally functioning connections in the Drosophila optic lamina. Flies with mutations in the gap junction genes (innexins), shakingB, and ogre have normal photoreceptor potentials but a defective response of the postsynaptic cells in the optic lamina. This is indicated by a reduction in, or absence of, transients in the electroretinogram. Ogre is required in the presynaptic retinal photoreceptors. ShakingB(N) is, at a minimum, required in postsynaptic lamina neurons. Transgenic expression of the appropriate innexins during pupal development (but not later) rescues connection defects. Transient gap junctions have been observed to precede chemical synapse formation and have been hypothesized to play a role in connectivity and synaptogenesis; however, no causal role has been demonstrated. Here we show that developmental gap junction genes can be required for normally functioning neural connections to form.

Animals↗
PubMed2006

Intracellular sterol transport in eukaryotes, a connection to mitochondrial function?

Eukaryotic cells synthesize sterols in the endoplasmatic reticulum (ER) from where it needs to be efficiently transported to the plasma membrane, which harbors approximately 90% of the free sterol pool of the cell. Sterols that are being taken up from the environment, on the other hand, are transported back from the plasma membrane to the ER, where the free sterols are esterified to steryl esters. The molecular mechanisms that govern this bidirectional movement of sterols between the ER and the plasma membrane of eukaryotic cells are only poorly understood. Proper control of this transport is important for normal cell function and development as indicated by fatal human pathologies such as Niemann Pick type C disease and atherosclerosis, which are characterized by an over-accumulation of free sterols within endosomal membranes and the ER, respectively. Recently, a number of complementary approaches using Saccharomyces cerevisiae as a model organism lead to a more precise characterization of the pathways that control the subcellular transport of sterols and led to the identification of components that directly or indirectly affect sterol uptake at the plasma membrane and its transport back to the ER. A genetic approach that is based on the fact that yeast is a facultative anaerobic organism, which becomes auxotrophic for sterols in the absence of oxygen, resulted in the identification of 17 genes that are required for efficient uptake and/or transport of sterols. Unexpectedly, many of these genes are required for mitochondrial functions. A possible connection between mitochondrial biogenesis and sterol biosynthesis and uptake will be discussed in light of the fact that cholesterol transport into the inner membranes of mitochondria is a well established sterol transport route in vertebrates, where it is required to convert cholesterol into pregnenolone, the precursor of steroids.

Animals↗
PubMed2001

Circadian rhythm of melatonin, corticosterone and phagocytosis: effect of stress.

Melatonin has a functional connection with the immune system. Phagocyte function is altered by extirpation of the pineal gland, one source of melatonin, or by in vitro incubation of phagocytes with pharmacological concentrations of melatonin. Given that its synthesis by pinealocytes is under the control of the noradrenaline released by the sympathetic postganglionaric nerve endings, the present work was aimed at evaluating the circadian rhythm of melatonin, corticosterone, and phagocytosis in BALB/c mice in basal and stress situations. Peritoneal macrophages were used as phagocytes, latex beads as the particles to be ingested, and forced swimming to exhaustion as the stress situation. Radioimmunoassay was used to determine the animals' serum hormone levels. Samples were taken every 3 hr in the period from 04:00 to 22:00 hr, and every 30 min during the remaining period from 22:00 to 04:00 hr. Control mice presented a short-term melatonin peak at 23:30 hr, while the maximum inert-particle ingestion capacity of the peritoneal macrophages also occurred during the night but at 03:30 hr. The corticosterone levels in control mice presented a circadian rhythm with a day-time maximum peak (16:00 hr). Compared with the controls, the animals subjected to stress maintained, although at lower values, the melatonin peak at 23:30 hr, but they presented a loss of the rhythm of serum corticosterone levels, and the corticosterone levels and the macrophage phagocytic capacity were greater at all hours of the day.

Animals↗
PubMed2003

Enteric glia promote functional recovery of CTM reflex after dorsal root transection.

Transected dorsal root axons of adult rats can be induced to regenerate through the normally non-permissive environment of the dorsal root entry zone (DREZ) into the spinal cord by implanting enteric glia (EG) into the DREZ. We have now examined whether the regenerating central axons make functional connections by studying the return of function of a behavioral response, the cutaneous trunci muscle (CTM) reflex. Implantation of EG into the spinal cord DREZ led to functional recovery of the CTM reflex in 82%, 72% and 70% of animals 1, 2 and 3 months, respectively, after injury. In contrast, the CTM reflex did not recover in animals implanted with 3T3 or C6 glioma cells or with vehicle only.

3T3 Cells↗
PubMedDate not supplied

[Reactions of visual cortex neurons to painful stimulation].

Responses of 18 neurones of the first cortical projection visual area to photic and nociceptive stimulation (plunging of a paw into hot water) were studied in immobilized cats. The increase in blood pressure recorded in the femoral artery served as index of pain response. During plunging the paw into hot water 14 neurones showed an increase in the frequency of spike activity by 3 times as compared to the background. The changes in spike activity preceded the increase in the arterial pressure by 1-2 sec. 12 out of 14 neurones also responded to a photic stimulus. After administration of chlorpromazin the neuronal response to the nociceptive stimulus was blocked, but the response to the photic stimulus persisted. A conclusion is made that pain excitation reaches cortical visual neurones through functional connections, which are different from those functioning during activation of the same neurones with specific photic stimulus.

Animals↗
PubMed1990

A neural network simulation of simultaneous single-unit activity recorded from the dragonfly ganglia.

Techniques are described that allow the use of multiple neuron spike data in a computational neural network architecture. The network architecture was devised to match the number of actual neurons from which data were obtained. The network was successfully trained to accurately predict the multiple neuron spike trains. Simultaneous spike histories of 44 neurons were modeled by a network architecture consisting of 44 input units, 88 hidden units with recurrent connections and 44 output units. The activation function of each unit was determined by data unique to a single neuron. These data were coupled with an analog gradient that preserved both the exact spiking times and the relative spiking tendency of each neuron. The input activation values were compared to network output target values calculated to occur 5 msec forward in the composite spiking records of all neurons. Following 2000 training cycles with the gradient data, the average error of each unit in the network was 0.0016. Discrete output values for each network unit were correlated with those of all other units. These correlations were comparable to those done using the actual neuron data. Both correlations reveal a functional connectivity pattern among the units and neurons. These connectivity patterns indicate that the networks may synthesize patterns of activity needed for biological function; in this case, flight patterns carried out in the mesothoracic ganglion of the dragonfly. This model represents, to the best of our knowledge, the first computer based network simulation using actual experimental neural data obtained from a large number of spontaneously active cells in a small intact ganglion.

Action Potentials↗
PubMed2004

Astrocytic connectivity in the hippocampus.

Little is known about the functional connectivity between astrocytes in the CNS. To explore this issue we photo-released glutamate onto a single astrocyte in murine hippocampal slices and imaged calcium responses. Photo-release of glutamate causes a metabotropic glutamate receptor (mGluR)-dependent increase in internal calcium in the stimulated astrocyte and delayed calcium elevations in neighboring cells. The delayed elevation in calcium was not caused by either neuronal activity following synaptic transmission or by glutamate released from astrocytes. However, it was reduced by flufenamic acid (FFA), which is consistent with a role for adenosine triphosphate (ATP) release from astrocytes as an intercellular messenger. Exogenous ligands such as ATP (1 mircoM) increased the number of astrocytes that were recruited into coupled astrocytic networks, indicating that extracellular accumulation of neurotransmitters modulates neuronal excitability, synaptic transmission and functional coupling between astrocytes.

Journal Article↗
PubMed1999

How do cell assemblies encode information in the brain?

The present review discusses why cell-assembly coding, i.e. ensemble coding by functionally connected neurons, is a tenable view of the brain's neuronal code and how it operates in the working brain. The cell-assembly coding has two major properties, i.e., partial overlapping of neurons among assemblies and connection dynamics within and among the assemblies. The former is the ability of one neuron to participate in different types of information processing. The latter is the capability for functional synaptic connections, detected by activity correlations of the neurons, to change among different types of information processing. An example of a series of experiments which detected these two major properties is then given. Several relevant points concerning the detection of the actual dynamics of cell-assembly coding are also enumerated. They include the dependence of the type of cell-assembly coding on types of information-processing in different structures of the brain, sparse coding by distributed overlapped assemblies, and coincidence detection as a role of individual neurons to bind distributed neurons into cell assemblies.

Animals↗