Kainate-induced genes in the hippocampus: lessons from expression patterns

Kainate, the analog of the excitatory amino acid L-glutamate, upon binding to non-NMDA glutamate receptors, causes depolarization of neurons followed by severe status epilepticus, neurodegeneration, plasticity and gliosis. These events are best observed in hippocampus, the limbic structure implicated in learning and long-term memory formation. Neurons in all hippocampal structures undergo hyper-activation, however, whereas the cells in the CA subfields degenerate within 2--3 days following the application of kainate, the granule cells of the dentate gyrus are resistant to any form of neurodegeneration and even initiate new synaptic contacts. These physiological and histological changes are modulated by short-term and long-term alterations in gene expression. Perhaps close examination of the changing spatio-temporal patterns of mRNAs of various genes may help in generating a clearer picture of the molecular events leading to complex cognitive functions.     

The hippocampus and memory: insights from spatial processing

The hippocampus appears to be crucial for long-term episodic memory, yet its precise role remains elusive. Electrophysiological studies in rodents offer a useful starting point for developing models of hippocampal processing in the spatial domain. Here we review one such model that points to an essential role for the hippocampus in the construction of mental images. We explain how this neural-level mechanistic account addresses some of the current controversies in the field, such as the role of the hippocampus in imagery and short-term memory, and discuss its broader implications for the neural bases of episodic memory.     

Decoding mental states from brain activity in humans

Recent advances in human neuroimaging have shown that it is possible to accurately decode a person's conscious experience based only on non-invasive measurements of their brain activity. Such 'brain reading' has mostly been studied in the domain of visual perception, where it helps reveal the way in which individual experiences are encoded in the human brain. The same approach can also be extended to other types of mental state, such as covert attitudes and lie detection. Such applications raise important ethical issues concerning the privacy of personal thought.     

The ecology of the avian brain: food-storing memory and the hippocampus

Some species of birds store food, often hoarding several hundreds of seeds over a period of just a few weeks. Field and laboratory studies have demonstrated that food-storing species have an impressive memory and an enlarged region of the brain, the hippocampal region. Lesion experiments have shown that the hippocampus is important in accurate retrieval of stored food. Taken together, these results have led to the hypothesis that the enlarged hippocampus is associated with the memory requirements of retrieving stored food. In this review, we discuss four areas of study: comparative studies of the brain, comparative studies of behaviour, developmental plasticity and seasonal changes in food storing and the hippocampus.     

The ecology of the avian brain: food-storing memory and the hippocampus

Some species of birds store food, often hoarding several hundreds of seeds over a period of just a few weeks. Field and laboratory studies have demonstrated that food-storing species have an impressive memory and an enlarged region of the brain, the hippocampal region. Lesion experiments have shown that the hippocampus is important in accurate retrieval of stored food. Taken together, these results have led to the hypothesis that the enlarged hippocampus is associated with the memory requirements of retrieving stored food. In this review, we discuss four areas of study: comparative studies of the brain, comparative studies of behaviour, developmental plasticity and seasonal changes in food storing and the hippocampus.     

Positional information in neural map development: lessons from the olfactory system

Positional information is fundamental in development. Although molecular gradients are thought to represent positional information in various systems, the molecular logic used to interpret these gradients remains controversial. In the nervous system, sensory maps are formed in the brain based on gradients of axon guidance molecules. However, it remains unclear how axons find their targets based on relative, not absolute, expression levels of axon guidance receptors. No model solely based on axon-target interactions explains this point. Recent studies in the olfactory system suggested that the neural map formation requires axon-axon interactions, which is known as axon sorting. This review discusses how axon-axon and axon-target interactions interpret molecular gradients and determine the axonal projection sites in neural map formation.     

Cross-referencing radiation hybrid data to the recombination map: lessons from mouse chromosome 18

We are building a framework map of known-order anchor markers between the mouse T31 radiation hybrid (RH) panel and the recombination map based on The Jackson Laboratory (TJL) interspecific backcross panels using the established genetic order to evaluate and strengthen the RH results. In making this map comparison, we have elucidated several problems inherent in RH mapping and minimized these by careful attention to data gathering and interpretation methods. We describe lessons and pitfalls of developing radiation hybrid maps, using the example of mouse Chromosome 18, for which we have built a framework map of microsatellite anchor loci spanning the entire chromosome at significant LOD with no gaps. Sixty-five D18Mit- simple sequence length polymorphism (SSLP) markers form a continuous linkage along the T31 RH Chromosome 18 (RH map length 1598 cR, genetic length 41 cM) with all LODs greater than 6. These markers are also placed on TJL interspecific backcrosses, and the order of the markers in the two systems is in complete agreement. We are continuing to cross-reference the RH data to TJL backcross data for the other mouse chromosomes to improve further the power of RH mapping and to integrate more precisely the extensive existing recombination mapping data for the mouse with the incoming radiation hybrid map data.     

Decoding semi-constrained brain activity from FMRI using support vector machines and gaussian processes

Predicting a particular cognitive state from a specific pattern of fMRI voxel values is still a methodological challenge. Decoding brain activity is usually performed in highly controlled experimental paradigms characterized by a series of distinct states induced by a temporally constrained experimental design. In more realistic conditions, the number, sequence and duration of mental states are unpredictably generated by the individual, resulting in complex and imbalanced fMRI data sets. This study tests the classification of brain activity, acquired on 16 volunteers using fMRI, during mental imagery, a condition in which the number and duration of mental events were not externally imposed but self-generated. To deal with these issues, two classification techniques were considered (Support Vector Machines, SVM, and Gaussian Processes, GP), as well as different feature extraction methods (General Linear Model, GLM and SVM). These techniques were combined in order to identify the procedures leading to the highest accuracy measures. Our results showed that 12 data sets out of 16 could be significantly modeled by either SVM or GP. Model accuracies tended to be related to the degree of imbalance between classes and to task performance of the volunteers. We also conclude that the GP technique tends to be more robust than SVM to model unbalanced data sets.     

T-cell memory: lessons from Epstein-Barr virus infection in man

Epstein-Barr virus offers an ideal opportunity to follow the human T-cell response to a virus infection over time from its acute primary phase, as seen in infectious mononucleosis patients, into the memory phase that accompanies life-long virus persistence. Here we review recent evidence on the development and maturation of cytotoxic T-cell memory using this viral system.     

Understanding autism: insights from mind and brain

Autism is a developmental disorder characterized by impaired social interaction and communication as well as repetitive behaviours and restricted interests. The consequences of this disorder for everyday life adaptation are extremely variable. The general public is now more aware of the high prevalence of this lifelong disorder, with ca. 0.6% of the population being affected. However, the signs and symptoms of autism are still puzzling. Since a biological basis of autism was accepted, approaches from developmental cognitive neuroscience have been applied to further our understanding of the autism spectrum. The study of the behavioural and underlying cognitive deficits in autism has advanced ahead of the study of the underlying brain abnormalities and of the putative genetic mechanisms. However, advances in these fields are expected as methodological difficulties are overcome. In this paper, recent developments in the field of autism are outlined. In particular, we review the findings of the three main neuro-cognitive theories of autism: theory-of-mind deficit, weak central coherence and executive dysfunction.     

Brain electrical activity mapping: an exploratory study of infant response to odours

This mainly methodological paper describes the novel use ofan established EEG-based brain imaging technique (Brain ElectricalActivity Mapping or BEAM) to explore human infant responsesto odours. The aim of this study was to evaluate BEAM as aninvestigative tool in infant olfaction. A small sample of 3-month-oldinfants was tested in a low ambient odour environment. The infants'cortical responses to a number of proprietary baby-food odourswere recorded. Two experimental hypotheses were addressed. Thefirst concerned relative differences in cortical response beforeand during odour presentation. The second hypothesis statedthat differences would be seen between the various odorants.The overall results supported the first hypothesis. ¹Present address: School of Psychology, University of Birmingham,Birmingham B15 2TT, UK     

Spatial constancy and the brain: insights from neural networks

To form an accurate internal representation of visual space, the brain must accurately account for movements of the eyes, head or body. Updating of internal representations in response to these movements is especially important when remembering spatial information, such as the location of an object, since the brain must rely on non-visual extra-retinal signals to compensate for self-generated movements. We investigated the computations underlying spatial updating by constructing a recurrent neural network model to store and update a spatial location based on a gaze shift signal, and to do so flexibly based on a contextual cue. We observed a striking similarity between the patterns of behaviour produced by the model and monkeys trained to perform the same task, as well as between the hidden units of the model and neurons in the lateral intraparietal area (LIP). In this report, we describe the similarities between the model and single unit physiology to illustrate the usefulness of neural networks as a tool for understanding specific computations performed by the brain.     

Linking beta diversity patterns to protected areas: lessons from the Brazilian Atlantic Rainforest

Understanding the processes that drive patterns of beta diversity is crucial for planning conservation policies and for designing networks of protected area (PAs). Beta diversity can be decomposed into two components: 1—species turnover, the replacement of species by others resulting in a low proportion of shared species; 2—species nestedness—the result of differences in species richness, when a poorer community is a subset of species from a richer community. We aimed to evaluate beta diversity patterns and how they are represented in the network of PAs in southern Brazilian, regarding three forest types: Atlantic Forest s.s., Araucaria Forest, and Seasonal Forest. Beta diversity was partitioned into the turnover and nestedness components. Additionally, we examined spatial patterns of site similarity using distance decay curves. Beta diversity was mainly caused by species turnover (approx. 86%), with only a small contribution of nestedness (approx. 5%) in all three forests types. The patterns of distance decay curves revealed that even at small distances (50–100 km), we found a considerable decrease in similarities, reinforcing turnover patterns. As turnover brought the larger contribution to beta diversity, additional conservation efforts must target an increase in the number of PAs, that should be spread across each one of the regions, to maximize the protection of species diversity. Most of the PAs are currently limited to the eastern region and prioritize the Atlantic Forest s.s. Thus Araucaria Forest and Seasonal Forest should deserve special priority in new conservation actions, as they also contain high levels of species turnover.     

Higher brain functions of PACAP and a homologous Drosophila memory gene amnesiac: insights from knockouts and mutants

Neuropeptides usually exert a long-lived modulatory effect on the small-molecule neurotransmitters with which they colocalize via regulation of the response times of second messenger systems. Pituitary adenylate cyclase-activating polypeptide (PACAP) functions as a neuromodulator and neurotransmitter and regulates a variety of physiological processes. PACAP is structurally highly conserved during evolution, implying its vital importance. In Drosophila, loss-of-function mutations in a PACAP-like neuropeptide gene, amnesiac (amn), affect both memory retention and ethanol sensitivity. The amnesiac gene is expressed in neurons innervating the mushroom body lobes, the olfactory associative learning center. Conditional genetic ablation of neurotransmitter release from these neurons mimics the amnesiac memory phenotypes, suggesting an acute role for amnesiac in memory. However, genetic rescue experiments also suggest developmental defects in amnesiac mutants, implying a role in neuronal development. There is a parallel between memory formation in Drosophila and mammals. PACAP-specific (PAC(1)) receptor-deficient mice show a deficit in hippocampus-dependent associative learning and mossy fiber long-term potentiation (LTP). Meanwhile, PACAP-deficient mice display a high early mortality rate and additional CNS phenotypes including behavioral and psychological phenotypes (e.g., hyperlocomotion, intense novelty-seeking behavior, and explosive jumping). A functional comparison between PACAP and amnesiac underlines phylogenetically conserved functions across phyla and may provide insights into the possible mechanisms of action and evolution of this neuropeptidergic system.     

Chromatin domains in higher eukaryotes: insights from genome-wide mapping studies

In genomes of higher eukaryotes, adjacent genes often show coordinated regulation of their expression. Compartmentalization of multiple neighboring genes into a shared chromatin environment can facilitate this coordinated expression. New mapping techniques have begun to reveal that such multigene chromatin domains are a common feature of fly and mammalian genomes. Many different types of chromatin domains have been identified based on the genomic binding patterns of various proteins and histone modifications. In addition, maps of genome–nuclear lamina associations and of looping interactions between loci provide the first systematic views of the three-dimensional folding of interphase chromosomes. These genome-wide datasets uncover new architectural principles of eukaryotic genomes and indicate that multigene chromatin domains are prevalent and important regulatory units.     

Invasive recordings from the human brain: clinical insights and beyond

Although non-invasive methods such as functional magnetic resonance imaging, electroencephalograms and magnetoencephalograms provide most of the current data about the human brain, their resolution is insufficient to show physiological processes at the cellular level. Clinical approaches sometimes allow invasive recordings to be taken from the human brain, mainly in patients with epilepsy or with movement disorders, and such recordings can sample neural activity at spatial scales ranging from single cells to distributed cell assemblies. In addition to their clinical relevance, these recordings can provide unique insights into brain functions such as movement control, perception, memory, language and even consciousness.     

Brain targeting through the autonomous nervous system: lessons from prion diseases

The human central nervous system (CNS) is targeted by diverse pathogens that use distinct pathways to bypass the blood-brain barrier, such as trafficking into the brain via infected blood cells or using retrograde axonal transport through sensory or motor fibers. Prions are transmissible agents that induce a devastating subacute neurodegeneration when they successfully reach the CNS. Two recent studies focusing on pathways of prion neuroinvasion provide converging evidence that, in the case of peripheral transmission, such as human consumption of contaminated tissue, the infectious agent uses the sympathetic noradrenergic neurons to reach the CNS after early replication in lymphoid tissues.     

Multineuronal firing patterns in the signal from eye to brain

Population codes in the brain have generally been characterized by recording responses from one neuron at a time. This approach will miss codes that rely on concerted patterns of action potentials from many cells. Here we analyze visual signaling in populations of ganglion cells recorded from the isolated salamander retina. These neurons tend to fire synchronously far more frequently than expected by chance. We present an efficient algorithm to identify what groups of cells cooperate in this way. Such groups can include up to seven or more neurons and may account for more than 50% of all the spikes recorded from the retina. These firing patterns represent specific messages about the visual stimulus that differ significantly from what one would derive by single-cell analysis.