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Front Neurosci [journal]
- Foraging across the life span: is there a reduction in exploration with aging? [Journal Article]
- Front Neurosci 2013.:53.
Does foraging change across the life span, and in particular, with aging? We report data from two foraging tasks used to investigate age differences in search in external environments as well as internal search in memory. Overall, the evidence suggests that foraging behavior may undergo significant changes across the life span across internal and external search. In particular, we find evidence of a trend toward reduced exploration with increased age. We discuss these findings in light of theories that postulate a link between aging and reductions in novelty seeking and exploratory behavior.
- Review: regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH) synthesis and release in photoperiodic animals. [Journal Article]
- Front Neurosci 2013.:60.
Gonadotropin-inhibitory hormone (GnIH) is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH) neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R), GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG) axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin, and glucocorticoids, to control avian and mammalian reproduction.
- The Nav1.9 channel regulates colonic motility in mice. [Journal Article]
- Front Neurosci 2013.:58.
The colonic migrating motor complex (CMMC) is a major pattern of motility that is entirely generated and organized by the enteric nervous system. We have previously demonstrated that the Nav1.9 channel underlies a tetrodotoxin-resistant sodium current which modulates the excitability of enteric neurons. The aim of this study was to observe the effect of loss of the Nav1.9 channel in enteric neurons on mouse colonic motility in vitro. The mechanical activity of the circular muscle was simultaneously recorded from three sites, namely, proximal, mid- and distal, along the whole colon of male, age-matched wild-type and Nav1.9 null mice. Spontaneous CMMCs were observed in all preparations. The mean frequency of CMMCs was significantly higher in the Nav1.9 null mice (one every 2.87 ± 0.1 min compared to one every 3.96 ± 0.23 min in the wild type). The mean duration of CMMCs was shorter and the mean area-under-contraction was larger in the Nav1.9 null mice compared to the wild type. In addition, CMMCs propagated preferentially in an aboral direction in the Nav1.9 null mice. Our study demonstrates that CMMCs do occur in mice lacking the Nav1.9 channel, but their characteristics are significantly different from controls. Up to now, the Nav1.9 channel was mainly associated with nociceptive neurons and involved in their hyperexcitability after inflammation. Our result shows for the first time a role for the Nav1.9 channel in a complex colonic motor pattern.
- Hippocampus-dependent learning influences hippocampal neurogenesis. [Journal Article]
- Front Neurosci 2013.:57.
The structure of the mammalian hippocampus continues to be modified throughout life by continuous addition of neurons in the dentate gyrus. Although the existence of adult neurogenesis is now widely accepted the function that adult generated granule cells play is a topic of intense debate. Many studies have argued that adult generated neurons, due to unique physiological characteristics, play a unique role in hippocampus-dependent learning and memory. However, it is not currently clear whether this is the case or what specific capability adult generated neurons may confer that developmentally generated neurons do not. These questions have been addressed in numerous ways, from examining the effects of increasing or decreasing neurogenesis to computational modeling. One particular area of research has examined the effects of hippocampus dependent learning on proliferation, survival, integration and activation of immature neurons in response to memory retrieval. Within this subfield there remains a range of data showing that hippocampus dependent learning may increase, decrease or alternatively may not alter these components of neurogenesis in the hippocampus. Determining how and when hippocampus-dependent learning alters adult neurogenesis will help to further clarify the role of adult generated neurons. There are many variables (such as age of immature neurons, species, strain, sex, stress, task difficulty, and type of learning) as well as numerous methodological differences (such as marker type, quantification techniques, apparatus size etc.) that could all be crucial for a clear understanding of the interaction between learning and neurogenesis. Here, we review these findings and discuss the different conditions under which hippocampus-dependent learning impacts adult neurogenesis in the dentate gyrus.
- Reward-related activity in the medial prefrontal cortex is driven by consumption. [Journal Article]
- Front Neurosci 2013.:56.
An emerging literature suggests that the medial prefrontal cortex (mPFC) is crucial for the ability to track behavioral outcomes over time and has a critical role in successful foraging. Here, we examine this issue by analyzing changes in neuronal spike activity and local field potentials in the rat mPFC in relation to the consumption of rewarding stimuli. Using multi-electrode recording methods, we simultaneously recorded from ensembles of neurons and field potentials in the mPFC during the performance of an operant-delayed alternation task and a variable-interval licking procedure. In both tasks, we found that consummatory behavior (licking) activates many mPFC neurons and is associated with theta-band phase locking by mPFC field potentials. Many neurons that were modulated by the delivery of reward were also modulated when rats emitted bouts of licks during the period of consumption. The majority of these licking-modulated neurons were found in the rostral part of the prelimbic cortex, a region that is heavily interconnected with the gustatory insular cortex and projects to subcortical feeding-related centers. Based on the tight coupling between spike activity, theta-band phase locking, and licking behavior, we suggest that reward-related activity in the mPFC is driven by consummatory behavior.
- Optogenetic approaches for functional mouse brain mapping. [Journal Article]
- Front Neurosci 2013.:54.
To better understand the connectivity of the brain, it is important to map both structural and functional connections between neurons and cortical regions. In recent years, a set of optogenetic tools have been developed that permit selective manipulation and investigation of neural systems. These tools have enabled the mapping of functional connections between stimulated cortical targets and other brain regions. Advantages of the approach include the ability to arbitrarily stimulate brain regions that express opsins, allowing for brain mapping independent of behavior or sensory processing. The ability of opsins to be rapidly and locally activated allows for investigation of connectivity with spatial resolution on the order of single neurons and temporal resolution on the order of milliseconds. Optogenetic methods for functional mapping have been applied in experiments ranging from in vitro investigation of microcircuits, to in vivo probing of inter-regional cortical connections, to examination of global connections within the whole brain. We review recently developed functional mapping methods that use optogenetic single-point stimulation in the rodent brain and employ cellular electrophysiology, evoked motor movements, voltage sensitive dyes (VSDs), calcium indicators, or functional magnetic resonance imaging (fMRI) to assess activity. In particular we highlight results using red-shifted organic VSDs that permit high temporal resolution imaging in a manner spectrally separated from Channelrhodopsin-2 (ChR2) activation. VSD maps stimulated by ChR2 were dependent on intracortical synaptic activity and were able to reflect circuits used for sensory processing. Although the methods reviewed are powerful, challenges remain with respect to finding approaches that permit selective high temporal resolution assessment of stimulated activity in animals that can be followed longitudinally.
- Perspective: Identification of genetic variants associated with dopaminergic compensatory mechanisms in early Parkinson's disease. [Journal Article]
- Front Neurosci 2013.:52.
Parkinson's disease (PD) is slowly progressive, and heterogeneity of its severity among individuals may be due to endogenous mechanisms that counterbalance the striatal dopamine loss. In this perspective paper, we introduce a neuroimaging-genetic approach to identify genetic variants, which may contribute to this compensation. First, we briefly review current known potential compensatory mechanisms for premotor and early disease PD, located in the striatum and other brain regions. Then, we claim that a mismatch between mild symptomatic disease, manifested by low motor score on the Unified PD Rating Scale (UPDRS), and extensive Nigro-Striatal (NS) degeneration, manifested by reduced uptake of [(123)I]FP-CIT, is indicative of compensatory processes. If genetic variants are associated with the severity of motor symptoms, while the level of striatal terminals degeneration measured by ligand uptake is taken into account and controlled in the analysis, then these variants may be involved in functional compensatory mechanisms for striatal dopamine deficit. To demonstrate feasibility of this approach, we performed a small "proof of concept" study (candidate gene design) in a sample of 28 Jewish PD patients, and preliminary results are presented.
- A Framework for Linear and Non-Linear Registration of Diffusion-Weighted MRIs Using Angular Interpolation. [Journal Article]
- Front Neurosci 2013.:41.
Registration of diffusion-weighted magnetic resonance images (DW-MRIs) is a key step for population studies, or construction of brain atlases, among other important tasks. Given the high dimensionality of the data, registration is usually performed by relying on scalar representative images, such as the fractional anisotropy (FA) and non-diffusion-weighted (b0) images, thereby ignoring much of the directional information conveyed by DW-MR datasets itself. Alternatively, model-based registration algorithms have been proposed to exploit information on the preferred fiber orientation(s) at each voxel. Models such as the diffusion tensor or orientation distribution function (ODF) have been used for this purpose. Tensor-based registration methods rely on a model that does not completely capture the information contained in DW-MRIs, and largely depends on the accurate estimation of tensors. ODF-based approaches are more recent and computationally challenging, but also better describe complex fiber configurations thereby potentially improving the accuracy of DW-MRI registration. A new algorithm based on angular interpolation of the diffusion-weighted volumes was proposed for affine registration, and does not rely on any specific local diffusion model. In this work, we first extensively compare the performance of registration algorithms based on (i) angular interpolation, (ii) non-diffusion-weighted scalar volume (b0), and (iii) diffusion tensor image (DTI). Moreover, we generalize the concept of angular interpolation (AI) to non-linear image registration, and implement it in the FMRIB Software Library (FSL). We demonstrate that AI registration of DW-MRIs is a powerful alternative to volume and tensor-based approaches. In particular, we show that AI improves the registration accuracy in many cases over existing state-of-the-art algorithms, while providing registered raw DW-MRI data, which can be used for any subsequent analysis.
- Observations on the evolution of the melanocortin receptor gene family: distinctive features of the melanocortin-2 receptor. [Journal Article]
- Front Neurosci 2013.:28.
The melanocortin receptors (MCRs) are a gene family in the rhodopsin class of G protein-coupled receptors. Based on the analysis of several metazoan genome databases it appears that the MCRs are only found in chordates. The presence of five genes in the family (i.e., mc1r, mc2r, mc3r, mc4r, mc5r) in representatives of the tetrapods indicates that the gene family is the result of two genome duplication events and one local gene duplication event during the evolution of the chordates. The MCRs are activated by melanocortin ligands (i.e., ACTH, α-MSH, β-MSH, γ-MSH, δ-MSH) which are all derived from the polypeptide hormone/neuropeptide precursor, POMC, and as a result the functional evolution of the MCRs is intimately associated with the co-evolution of POMC endocrine and neuronal circuits. This review will consider the origin of the MCRs, and discuss the evolutionary relationship between MC2R, MC5R, and MC4R. In addition, this review will analyze the functional evolution of the mc2r gene in light of the co-evolution of the MRAP (Melanocortin-2 Receptor Accessory Protein) gene family.
- The role of leptin in the control of insulin-glucose axis. [Journal Article]
- Front Neurosci 2013.:51.
Obesity and diabetes mellitus are great public health concerns throughout the world because of their increasing incidence and prevalence. Leptin, the adipocyte hormone, is well known for its role in the regulation of food intake and energy expenditure. In addition to the regulation of appetite and satiety that recently has attracted much attentions, insight has also been gained into the critical role of leptin in the control of the insulin-glucose axis, peripheral glucose and insulin responsiveness. Since the discovery of leptin, leptin has been taken for its therapeutic potential to obesity and diabetes. Recently, the therapeutic effects of central leptin gene therapy have been reported in insulin-deficient diabetes in obesity animal models such as ob/ob mise, diet-induced obese mice, and insulin-deficient type 1 diabetes mice, and also in patients with inactivating mutations in the leptin gene. Herein, we review the role of leptin in regulating feeding behavior and glucose metabolism and also the therapeutic potential of leptin in obesity and diabetes mellitus.