Neural correlations, population coding and computation

How the brain encodes information in population activity, and how it combines and manipulates that activity as it carries out computations, are questions that lie at the heart of systems neuroscience. During the past decade, with the advent of multi-electrode recording and improved theoretical models, these questions have begun to yield answers. However, a complete understanding of neuronal variability, and, in particular, how it affects population codes, is missing. This is because variability in the brain is typically correlated, and although the exact effects of these correlations are not known, it is known that they can be large. Here, we review studies that address the interaction between neuronal noise and population codes, and discuss their implications for population coding in general.     

Neural correlates of decisions

Once considered the province of philosophy and the behavioral sciences, the process of making decisions has received increasing scrutiny from neurobiologists. Recent research suggests that sensory judgements unfold through the gradual accumulation of neuronal signals in sensory-motor pathways, favoring one alternative over others. Stored representations of the outcome of prior actions activate neurons in many of these same areas during decision-making. The challenge for neurobiologists lies in deciphering how signals from these disparate areas are integrated to form a single behavioral choice and the mechanisms responsible for selecting the appropriate information upon which decisions should be informed in particular contexts.     

Hepatic actions of levonorgestrel: correlations between biochemical and morphological findings

The influence of the synthetic sexual steroid levonorgestrel (LN) on rat liver in various doses and at different structural levels was investigated. A slight reactive hepatosis was found by histological examination after administration of LN in a dose of 10 mg per kg body wt. The same dose caused exclusively distinct lesions of the mitochondria, however, only in centrilobular parenchymal cells, whereas in the periportal hepatocytes only the lipid droplet content appears somewhat elevated. LN decreased the total glutathione content of the liver. The mitochondrial glutathione was decreased more intensively. One mg/kg body wt. of LN decreased the cytochrome P-450 content, but 10 mg/kg body wt. increased ethyl-morphine N-demethylation and 7-ethoxycoumarin O-deethylation activities. Distinct correlations could be shown between the biochemical changes and the ultrastructural findings.     

Neural signatures of evidence accumulation in temporal decisions

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Neural fate decisions mediated by trans-activation and cis-inhibition in Notch signaling

MOTIVATION: In the developing nervous system, the expression of proneural genes, i.e. Hes1, Neurogenin-2 (Ngn2) and Deltalike-1 (Dll1), oscillates in neural progenitors with a period of 2-3 h, but is persistent in post-mitotic neurons. Unlike the synchronization of segmentation clocks, oscillations in neural progenitors are asynchronous between cells. It is known that Notch signaling, in which Notch in a cell can be activated by Dll1 in neighboring cells (trans-activation) and can also be inhibited by Dll1 within the same cell (cis-inhibition), is important for neural fate decisions. There have been extensive studies of trans-activation, but the operating mechanisms and potential implications of cis-inhibition are less clear and need to be further investigated. RESULTS: In this article, we present a computational model for neural fate decisions based on intertwined dynamics with trans-activation and cis-inhibition involving the Hes1, Notch and Dll1 proteins. In agreement with experimental observations, the model predicts that both trans-activation and cis-inhibition play critical roles in regulating the choice between remaining as a progenitor and embarking on neural differentiation. In particular, trans-activation is essential for generation of oscillations in neural progenitors, and cis-inhibition is important for the asynchrony between adjacent cells, indicating that the asynchronous oscillations in neural progenitors depend on cooperation between trans-activation and cis-inhibition. In contrast, cis-inhibition plays more critical roles in embarking on neural differentiation by inactivating intercellular Notch signaling. The model presented here might be a good candidate for providing the first qualitative mechanism of neural fate decisions mediated by both trans-activation and cis-inhibition.     

Neural function: metabolism and actions of inositol metabolites in mammalian brain

In the nervous system, a variety of cell types respond to external stimuli through the inositol lipid signalling pathways. The stimulus-coupled sequence of intracellular events has been investigated in a homogeneous model system, the cloned mammalian neural cell line NG115-401L. The neural peptide bradykinin stimulates a rapid production of identified inositol phosphate isomers and an intracellular Ca2+ discharge followed by a persistent plasma membrane influx. The temporal sequence suggests that Ins(1,4,5)P3 or Ins(1,3,4,5)P4 or both may coordinate these events in a neuronal cell, as has been suggested in other cell types. Thapsigargin, an irritant and tumour-promoting plant product, produces calcium transients in the absence of inositol phosphate production, and may provide a new tool for investigating the interactions between inositol phosphates and changes in cellular calcium homeostasis. In the 401L line, high levels of radiolabelled InsP5 and InsP6 have been detected, which has led to the evaluation of their possible occurrence and actions in normal brain. Both InsP5 and InsP6 are produced from a radiolabelled myo-inositol precursor in intact mature brain in a region-specific manner. This suggests that both inositol polyphosphates may be end products of regionally regulated biosynthetic pathways. When microinjected into a nucleus of the brainstem, or iontophoretically applied to the dorsal horn of the spinal cord, both InsP5 and InsP6, but not Ins(1,3,4,5)P4 isomers, appear to be potent neural stimulants. These results suggest that the inositol lipid signalling pathways may generate both intracellular and extracellular signals in brain.     

Neural activation and functional connectivity during motor imagery of bimanual everyday actions

Bimanual actions impose intermanual coordination demands not present during unimanual actions. We investigated the functional neuroanatomical correlates of these coordination demands in motor imagery (MI) of everyday actions using functional magnetic resonance imaging (fMRI). For this, 17 participants imagined unimanual actions with the left and right hand as well as bimanual actions while undergoing fMRI. A univariate fMRI analysis showed no reliable cortical activations specific to bimanual MI, indicating that intermanual coordination demands in MI are not associated with increased neural processing. A functional connectivity analysis based on psychophysiological interactions (PPI), however, revealed marked increases in connectivity between parietal and premotor areas within and between hemispheres. We conclude that in MI of everyday actions intermanual coordination demands are primarily met by changes in connectivity between areas and only moderately, if at all, by changes in the amount of neural activity. These results are the first characterization of the neuroanatomical correlates of bimanual coordination demands in MI. Our findings support the assumed equivalence of overt and imagined actions and highlight the differences between uni- and bimanual actions. The findings extent our understanding of the motor system and may aid the development of clinical neurorehabilitation approaches based on mental practice.     

Neural substrates of sensory-guided locomotor decisions in the rat superior colliculus

Deciding in which direction to move is a ubiquitous feature of animal behavior, but the neural substrates of locomotor choices are not well understood. The superior colliculus (SC) is a midbrain structure known to be important for controlling the direction of gaze, particularly when guided by visual or auditory cues, but which may play a more general role in behavior involving spatial orienting. To test this idea, we recorded and manipulated activity in the SC of freely moving rats performing an odor-guided spatial choice task. In this context, not only did a substantial majority of SC neurons encode choice direction during goal-directed locomotion, but many also predicted the upcoming choice and maintained selectivity for it after movement completion. Unilateral inactivation of SC activity profoundly altered spatial choices. These results indicate that the SC processes information necessary for spatial locomotion, suggesting a broad role for this structure in sensory-guided orienting and navigation.     

Neural fate decisions mediated by combinatorial regulation of Hes1 and miR-9

In the nervous system, Hes1 shows an oscillatory manner in neural progenitors but a persistent one in neurons. Many models involving Hes1 have been provided for the study of neural differentiation but few of them take the role of microRNA into account. It is known that a microRNA, miR-9, plays crucial roles in modulating Hes1 oscillations. However, the roles of miR-9 in controlling Hes1 oscillations and inducing transition between different cell fates still need to be further explored. Here we provide a mathematical model to show the interaction between miR-9 and Hes1, with the aim of understanding how the Hes1 oscillations are produced, how they are controlled, and further, how they are terminated. Based on the experimental findings, the model demonstrates the essential roles of Hes1 and miR-9 in regulating the dynamics of the system. In particular, the model suggests that the balance between miR-9 and Hes1 plays important roles in the choice between progenitor maintenance and neural differentiation. In addition, the synergistic (or antagonistic) effects of several important regulations are investigated so as to elucidate the effects of combinatorial regulation in neural decision-making. Our model provides a qualitative mechanism for understanding the process in neural fate decisions regulated by Hes1 and miR-9.     

Decisions,decisions, decisions: choosing a biological science of choice

Behavioral ecologists argue that evolution drives animal behavior to efficiently solve the problems animals face in their environmental niches. The ultimate evolutionary causes of decision making, they contend, can be found in economic analyses of organisms and their environments. Neurobiologists interested in how animals make decisions have, in contrast, focused their efforts on understanding the neurobiological hardware that serves as a more proximal cause of that same behavior. Describing the flow of information within the nervous system without regard to these larger goals has been their focus. Recent work in a number of laboratories has begun to suggest that these two approaches are beginning to fuse. It may soon be possible to view the nervous system as a representational process that solves the mathematically defined economic problems animals face by making efficient decisions. These developments in the neurobiological theory of choice, and the new schema they imply, form the subject of this article.     

Decisions,decisions, decisions: the host colony choices of a social parasite

Many factors contribute to the success of a socially parasitic strategy, especially the ability of the parasite to invade a host colony. However, little research has focused on the choices that may be made by an invading parasite, specifically whether parasites actively discriminate between different host colonies and if they have a preference for colonies of a particular size. When an allodapine social parasite, Inquilina schwarzi, was presented with colonies of their host species, Exoneura robusta, the parasites were found to invade the larger host colonies. However, it could not be ascertained from this study whether the parasites were making an active decision concerning which colony to invade, or whether they were simply more attracted to the larger colonies due to potentially stronger odour cues. Regardless of the cause, the larger host colonies are more at risk of being invaded by a social parasite, which would give parasites greater resources for exploitation and could also provide selection against the large host colony sizes.     

Leech locomotion: swimming, crawling, and decisions

Research on the neuronal control of locomotion in leeches spans almost four decades. Recent advances reviewed here include discoveries that: (1) interactions between multiple hormones modulate initiation of swimming; (2) stretch receptors associated with longitudinal muscles interact with the central oscillator circuit via electrical junctions; (3) intersegmental interactions, according to theoretical analyses, must be relatively weak compared to oscillator interactions within ganglia; and (4) multiple interacting neurons control the expression of alternative modes of locomotion. The innovative techniques that facilitated these advances include optical recording of membrane potential changes, simultaneous intracellular injection of high and low molecular weight fluorescent dyes, and detailed modeling via an input-output systems engineering approach.     

Neural circuits underlying imitation learning of hand actions: an event-related fMRI study

The neural bases of imitation learning are virtually unknown. In the present study, we addressed this issue using an event-related fMRI paradigm. Musically naive participants were scanned during four events: (1) observation of guitar chords played by a guitarist, (2) a pause following model observation, (3) execution of the observed chords, and (4) rest. The results showed that the basic circuit underlying imitation learning consists of the inferior parietal lobule and the posterior part of the inferior frontal gyrus plus the adjacent premotor cortex (mirror neuron circuit). This circuit, known to be involved in action understanding, starts to be active during the observation of the guitar chords. During pause, the middle frontal gyrus (area 46) plus structures involved in motor preparation (dorsal premotor cortex, superior parietal lobule, rostral mesial areas) also become active. Given the functional properties of area 46, a model of imitation learning is proposed based on interactions between this area and the mirror neuron system.     

Genetic correlations, tradeoffs and environmental variation

Negative genetic correlations among traits are often used as evidence for tradeoffs that can influence evolutionary trajectories in populations. While there may be evidence for negative correlations within a particular environment, genetic correlations can shift when populations encounter different environmental conditions. Here we review the evidence for these shifts by focusing on experiments that have examined genetic correlations in more than one environment. In many studies, there are significant changes in correlations and these can even switch sign across environments. This raises questions about the validity of deducing genetic constraints from studies in one environment and suggests that the interaction between environmental conditions and the expression of genetic covariation is an important avenue for future work.     

Tooth,chin, bone and body size correlations

Correlations of size of teeth, chin, bone and body were investigated in 118 males and 102 females of the Burlington Growth Centre. In the males, the mesiodistal widths of the mandibular lateral incisors and canines were independently related to the thickness of the cortex of the second metacarpal and to body weight. Bone cortex thickness was significantly related to metacarpal width in males and to body weight in females. Chin depth of the males was significantly related to bone width and to body height, and negatively related to tooth width when bone width or body weight was held constant in partial correlations. Bone width and length were significantly related to body height in both sexes.