Higher Brain Regions Research Articles

Enriched Expression of GluD1 in Higher Brain Regions and Its Involvement in Parallel Fiber–Interneuron Synapse Formation in the Cerebellum

Of the two members of the δ subfamily of ionotropic glutamate receptors, GluD2 is exclusively expressed at parallel fiber-Purkinje cell (PF-PC) synapses in the cerebellum and regulates their structural and functional connectivity. However, little is known to date regarding cellular and synaptic expression of GluD1 and its role in synaptic circuit formation. In the present study, we investigated this issue by producing specific and sensitive histochemical probes for GluD1 and analyzing cerebellar synaptic circuits in GluD1-knock-out mice. GluD1 was widely expressed in the adult mouse brain, with high levels in higher brain regions, including the cerebral cortex, striatum, limbic regions (hippocampus, nucleus accumbens, lateral septum, bed nucleus stria terminalis, lateral habenula, and central nucleus of the amygdala), and cerebellar cortex. In the cerebellar cortex, GluD1 mRNA was expressed at the highest level in molecular layer interneurons and its immunoreactivity was concentrated at PF synapses on interneuron somata. In GluD1-knock-out mice, the density of PF synapses on interneuron somata was significantly reduced and the size and number of interneurons were significantly diminished. Therefore, GluD1 is common to GluD2 in expression at PF synapses, but distinct from GluD2 in neuronal expression in the cerebellar cortex; that is, GluD1 in interneurons and GluD2 in PCs. Furthermore, GluD1 regulates the connectivity of PF-interneuron synapses and promotes the differentiation and/or survival of molecular layer interneurons. These results suggest that GluD1 works in concert with GluD2 for the construction of cerebellar synaptic wiring through distinct neuronal and synaptic expressions and also their shared synapse-connecting function.

Identification of CNS neurons with polysynaptic connections to both the sympathetic and parasympathetic innervation of the submandibular gland.

Coordinated modulation of sympathetic and parasympathetic nervous activity is required for physiological regulation of tissue function. Anatomically, whilst the peripheral sympathetic and parasympathetic pathways are separate, the distribution of premotor neurons in higher brain regions often overlaps. This co-distribution would enable coordinated regulation and might suggest individual premotor neurons could project to both sympathetic and parasympathetic outflows. To investigate this one submandibular gland was sympathectomized. One of two isogenic strains of the pseudorabies virus, expressing different fluorophores, was injected into the cut sympathetic nerve and the other into the submandibular gland. Independent labeling of the peripheral sympathetic and parasympathetic pathways was observed. Dual-labeled neurons were observed in many CNS regions known to be involved in regulating salivary function. We propose these observations highlight a common pattern of organization of the CNS, providing the anatomical framework for the fine control of organ function required for homeostatic regulation and the coordination of organ responses to enable complex behaviors.

How Brain Circuits Adapt to Changes in Sensory Experience

The cerebral cortex, the outer portion of the brain, consists of a layered structure of neural tissue that contains the cell bodies of neurons and plays a key role in perception and cognition. Although cortical circuits throughout the brain share similarities, the patterns of connections among neurons in different brain regions can vary widely. Yet, relatively little is known about how region-specific wiring patterns relate to information processing in the brain. Specific neuronal connections can respond in independent and sometimes opposite ways to changes in sensory input. In a study published in PLOS Biology, Dennis Katzel and Gero Miesenbock of the University of Oxford investigated how wiring patterns in the brains of adult mice adapt to changes in sensory input. They found that distinct connections in neural networks responded in different ways to sensory changes, allowing neurons to continue to function optimally. The findings reveal a remarkable level of adaptability in cortical circuits of the adult brain. To examine how brain circuits adapt to changes in sensory experience, the researchers used optogenetic mapping, a technique that combines genetics and optics to precisely control the activity of individual neurons. Katzel and Miesenbock inserted channelrhodopsin, a light-sensitive receptor protein originally found in algae, into neurons, making them sensitive to activation by light of specific wavelengths. This allowed them to control the activity of these neurons and study their wiring patterns and function. The researchers first examined how neural circuits would change in response to sensory deprivation. They trimmed the whiskers of adult mice to deprive the animals of tactile sensation for two to three weeks, and then prepared slices from barrel cortex, a brain region involved in processing tactile information from the whiskers. The researchers stimulated neurons in barrel cortex and then recorded light-evoked neural activity to map out neuronal connections. They found that sensory deprivation caused an overall reduction in inhibitory neural activity in cortical circuits, consistent with previous findings in brain regions that process visual information. But this new study paints a more refined picture. Different neuronal connections responded in different ways to sensory deprivation. Neurons in layer 5 of barrel cortex stopped sending inhibitory signals to neurons in layer 2/3, making layer 2/3 neurons more excitable. This change may be an autoregulatory adaptation, because the lack of tactile signals from the whiskers had caused a sharp decrease in excitatory neural activity in barrel cortex. The release from inhibition could prevent a total shutdown of neural function, allowing neurons in layer 2/3 to continue to process even weak tactile signals in the wake of sensory deprivation. On the other hand, neurons in layer 1 sent more inhibitory signals to neurons in layer 2/3 in response to sensory deprivation. Because layer 1 neurons carry information from higher brain regions involved in complex perceptual and cognitive processes, this adaptation could reflect top-down suppression of unusual activity in layer 2/3 neurons, which were no longer responding normally after sensory deprivation. Moreover, these changes in cortical wiring patterns were entirely reversible. In a different experiment, the researchers trimmed the whiskers of adult mice for several weeks and then allowed the whiskers to regrow for four to five weeks before preparing the brain slices. The return to normal sensory stimulation restored the original level of inhibitory signals from neurons in layers 1 and 5 to neurons in layer 2/3. This finding suggests that changes in sensory stimulation do not destroy the underlying physical structure of neuronal connections, but rather modify the patterns of communication between neurons in cortical circuits. Taken together, the findings suggest that specific neuronal connections can respond in independent and sometimes opposite ways to changes in sensory input. Surprisingly, these reversible changes occur in adulthood, well past the time window during which neuronal connections are thought to adapt to environmental fluctuations. The ability of wiring motifs to change in sophisticated ways could reflect a self-regulating mechanism that ensures optimal neural function in cortical circuits despite changes in sensory experience. Katzel D, Miesenbock G (2014) Experience-Dependent Rewiring of Specific Inhibitory Connections in Adult Neocortex. doi:10.1371/journal.pbio.1001798

Preface

Respiration is not a separate motor system, but takes part in all basic survival mechanisms. This volume is the first that analyzes respiration in this framework.Respiration is one of the most basic motor activities crucial for survival of the individual. It is under total control of the central nervous system, which adjusts respiratory depth and frequency depending on the circumstances the individual finds itself. For this reason this volume not only reviews the basic control systems of respiration, located in the caudal brainstem, but also the higher brain regions, that change depth and frequency of respiration. Scientific knowledge of these systems is crucial for understanding the problems in the many patients suffering from respiratory failure.This well-established international series examines major areas of basic and clinical research within neuroscience, as well as emerging subfields.

A Distinct Boundary between the Higher Brain’s Susceptibility to Ischemia and the Lower Brain’s Resistance

Higher brain regions are more susceptible to global ischemia than the brainstem, but is there a gradual increase in vulnerability in the caudal-rostral direction or is there a discrete boundary? We examined the interface between `higher` thalamus and the hypothalamus the using live brain slices where variation in blood flow is not a factor. Whole-cell current clamp recording of 18 thalamic neurons in response to 10 min O2/glucose deprivation (OGD) revealed a rapid anoxic depolarization (AD) from which thalamic neurons do not recover. Newly acquired neurons could not be patched following AD, confirming significant regional thalamic injury. Coinciding with AD, light transmittance (LT) imaging during whole-cell recording showed an elevated LT front that initiated in midline thalamus and that propagated into adjacent hypothalamus. However, hypothalamic neurons patched in paraventricular nucleus (PVN, n= 8 magnocellular and 12 parvocellular neurons) and suprachiasmatic nucleus (SCN, n= 18) only slowly depolarized as AD passed through these regions. And with return to control aCSF, hypothalamic neurons repolarized and recovered their input resistance and action potential amplitude. Moreover, newly acquired hypothalamic neurons could be readily patched following exposure to OGD, with resting parameters similar to neurons not previously exposed to OGD. Thalamic susceptibility and hypothalamic resilience were also observed following ouabain exposure which blocks the Na+/K+ pump, evoking depolarization similar to OGD in all neuronal types tested. Finally, brief exposure to elevated [K+]o caused spreading depression (SD, a milder, AD-like event) only in thalamic neurons so SD generation is regionally correlated with strong AD. Therefore the thalamus-hypothalamus interface represents a discrete boundary where neuronal vulnerability to ischemia is high in thalamus (like more rostral neocortex, striatum, hippocampus). In contrast hypothalamic neurons are comparatively resistant, generating weaker and recoverable anoxic depolarization similar to brainstem neurons, possibly the result of a Na/K pump that better functions during ischemia.

Respiratory, metabolic and cardiac functions are altered by disinhibition of subregions of the medial prefrontal cortex

The prefrontal cortex (PFC) is referred to as the visceral motor cortex; however, little is known about whether this region influences respiratory or metabolic outflows. The aim of this study was to describe simultaneous changes in respiratory, metabolic and cardiovascular functions evoked by disinhibition of the medial PFC (mPFC) and adjacent lateral septal nucleus (LSN). In urethane-anaesthetized rats, bicuculline methiodide was microinjected (2 mm; GABA-A receptor antagonist) into 90 sites in the mPFC at 0.72-4.00 mm from bregma. Phrenic nerve amplitude and frequency, arterial pressure, heart rate, splanchnic and lumbar sympathetic nerve activities (SNA), expired CO2, and core and brown adipose tissue temperatures were measured. Novel findings included disturbances to respiratory rhythm evoked from all subregions of the mPFC. Injections into the cingulate cortex evoked reductions in central respiratory function exclusively, whereas in ventral sites, particularly the infralimbic region, increases in respiratory drive and frequency, and metabolic and cardiac outflows were evoked. Disinhibition of sites in surrounding regions revealed that the LSN could evoke cardiovascular changes accompanied by distinct oscillations in SNA, as well as increases in respiratory amplitude. We show that activation of neurons within the mPFC and LSN influence respiratory, metabolic and cardiac outflows in a site-dependent manner. This study has implications with respect to the altered PFC neuronal activity seen in stress-related and mental health disorders, and suggests how basic physiological systems may be affected.

Endocannabinoid system and pain: an introduction

The endocannabinoid (EC) system consists of two main receptors: cannabinoid type 1 receptor cannabinoid receptors are found in both the central nervous system (CNS) and periphery, whereas the cannabinoid type 2 receptor cannabinoid receptor is found principally in the immune system and to a lesser extent in the CNS. The EC family consists of two classes of well characterised ligands; the N-acyl ethanolamines, such as N-arachidonoyl ethanolamide or anandamide (AEA), and the monoacylglycerols, such as 2-arachidonoyl glycerol. The various synthetic and catabolic pathways for these enzymes have been (with the exception of AEA synthesis) elucidated. To date, much work has examined the role of EC in nociceptive processing and the potential of targeting the EC system to produce analgesia. Cannabinoid receptors and ligands are found at almost every level of the pain pathway from peripheral sites, such as peripheral nerves and immune cells, to central integration sites such as the spinal cord, and higher brain regions such as the periaqueductal grey and the rostral ventrolateral medulla associated with descending control of pain. EC have been shown to induce analgesia in preclinical models of acute nociception and chronic pain states. The purpose of this review is to critically evaluate the evidence for the role of EC in the pain pathway and the therapeutic potential of EC to produce analgesia. We also review the present clinical work conducted with EC, and examine whether targeting the EC system might offer a novel target for analgesics, and also potentially disease-modifying interventions for pathophysiological pain states.

Permutation entropy of scalp EEG: A tool to investigate epilepsies: Suggestions from absence epilepsies

ObjectiveWe used permutation entropy (PE) to disclose abnormalities of cerebral activity in patients with typical absences (TAs). MethodsWe evaluated 24 EEG of TA patients and 40 EEG of healthy subjects. PE was estimated channel by channel, with electrodes being divided into high-PE cluster (high randomness), low-PE cluster (low randomness), and neutral cluster. We compared PE between EEG of patients and controls, and between interictal and ictal EEG of patients. ResultsPatients showed a recurrent behavior of PE topography, with anterior brain regions constantly associated to high PE levels and posterior brain regions constantly associated to low PE levels, during both interictal and ictal phases. On the contrary, healthy controls had a random distribution of PE topography. ConclusionsIn patients with TAs, a higher randomness in fronto-temporal areas and a lower randomness in posterior areas occur during both interictal and ictal phases. Such abnormalities are in keeping with evidences from different morphological and functional studies showing multifocal brain changes in TA patients. SignificancePE seems to be a useful tool to disclose abnormalities of cerebral electric activity not revealed by conventional EEG recordings, opening interesting prospective for future studies.

Organization of antennal lobe‐associated neurons in adult Drosophila melanogaster brain

The primary olfactory centers of both vertebrates and insects are characterized by glomerular structure. Each glomerulus receives sensory input from a specific type of olfactory sensory neurons, creating a topographic map of the odor quality. The primary olfactory center is also innervated by various types of neurons such as local neurons, output projection neurons (PNs), and centrifugal neurons from higher brain regions. Although recent studies have revealed how olfactory sensory input is conveyed to each glomerulus, it still remains unclear how the information is integrated and conveyed to other brain areas. By using the GAL4 enhancer-trap system, we conducted a systematic mapping of the neurons associated with the primary olfactory center of Drosophila, the antennal lobe (AL). We identified in total 29 types of neurons, among which 13 are newly identified in the present study. Analyses of arborizations of these neurons in the AL revealed how glomeruli are linked with each other, how different PNs link these glomeruli with multiple secondary sites, and how these secondary sites are organized by the projections of the AL-associated neurons.

225 IF LEPTIN IS THE CULPRIT, IS ESTROGEN THE ANTAGONIST IN OBESITY ASSOCIATED HYPERTENSION?

Obesity increases the risk of hypertension and cardiovascular diseases developing. Our research shows that elevated leptin levels are essential in development of obesity associated hypertension. Obese leptin deficient children have significantly(p<0.01) lower blood pressure(BP) compared to weight and aged matched subjects. Obese male mice fed a high fat diet(HFD) are hypertensive(113.7±1.1mmHg) and tachycardic(577.5±4.8BPM) compared to weight matched leptin deficient(ob/ob:100.7±3.0mmHg,510±7.0BPM) and leptin receptor deficient db/db:103.5±1.7mmHg,519.7±8.0BPM) mice measured via radiotelemetry. The Dorso Medial Hypothalamus(DMH) region in the brain is critical for obesity associated hypertension as blocking leptin actions here with both a leptin receptor antagonist or Adeno Associated Viral/shRNA knockdown of DMH leptin receptors reduces the elevated BP. Female mice fed HFD develop metabolic syndrome, including insulin insensitivity and hypertension much slower compared to males, despite leptin levels in females being substantially higher per each gram of body fat. Why are females protected? Unlike female mice, obese male mice fed a HFD have (p<0.01) higher sympathetic nerve activity (SNA) indirectly measured as brown adipose tissue temperature(36.73±0.1°C) compared to lean male mice(35.96±0.1°C) and this is leptin driven. In female mice thermogenesis is significantly(p<0.05) increased once mice have all endogenous estrogen removed, via ovariectomy. Ovariectomized female mice that have been replaced with exogenous estrogen have significantly lower thermogenesis, most likely driven by reduced SNA. Interestingly every neuron expressing estrogen receptors in the hypothalamus(the region including the DMH) also expresses a leptin receptor. While leptin increases SNA in obesity, estrogen may counteract leptin's actions through neurons in higher brain regions, decreasing SNA and protecting from the development of hypertension.

MDMA and 5‐HT neurotoxicity: the empirical evidence for its adverse effects in humans – no need for translation

In this issue of the BJP, Green et al. suggest that animal data could not be used to predict the adverse effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans and that MDMA did not produce 5-HT neurotoxicity in the human brain. This proposal was, however, not accompanied by a review of the empirical evidence in humans. The neuroimaging data on 5-HT markers in abstinent recreational ecstasy/MDMA users are extensive and broadly consistent. Reduced levels of the 5-HT transporter (SERT) have been found by research groups worldwide using a variety of assessment measures. These SERT reductions occur across the higher brain regions and remain after controlling for potential confounds. There are also extensive empirical data for impairments in memory and higher cognition, with the neurocognitive deficits correlating with the extent of SERT loss. Hence, MDMA is clearly damaging to humans, with extensive empirical data for both structural and functional deficits.

Pure-tone auditory thresholds are not chronically elevated in multiple sclerosis.

Despite the fact that acute cases of multiple sclerosis (MS)-related pure-tone hearing loss have been reported in the literature, consensus is lacking as to the chronic influences of MS on pure-tone thresholds. Most studies examining such influences have been limited by small sample sizes, lack of statistical comparisons between patients and controls, and confounding of the hearing measure with influences from sex and age. To date, associations between pure-tone thresholds and central MS-related brain lesions have not been assessed. In this study, pure-tone thresholds ranging from 0.5 to 8 kHz were measured in 73 MS patients and 73 individually age- and gender-matched normal controls. In 63 MS patients, correlations were computed between the threshold values and MRI-determined lesion activity in 26 central brain regions. Although thresholds were strongly influenced by sex, age, and tonal frequency, no meaningful influences of MS were discerned. Moreover, no significant association between the threshold values and central MS-related lesion activity was evident in any brain region evaluated. This study, the largest on this topic to use carefully matched control subjects and the sole study to assess relationships between auditory thresholds and central MS-related lesions, strongly suggests that (a) MS is not chronically associated with pure-tone hearing loss and (b) pure-tone thresholds are unrelated to MS lesion activity in higher brain regions. These findings, along with general reports from the literature, support the concept that when MS-related hearing threshold deficits are found, they are episodic and primarily dependent on lesions within the eighth nerve or brainstem.

Neuropsychological Aspects of Enhancing the Will

1. IntroductionThe will is an executive process involving the formation and translation of mental states into choices and actions. Some philosophers have defined the will as the mental act of trying.1 Neuroscientists tend to define it as neurobiologically based volition associated with unconscious brain processes underlying basic actions.2 Yet it seems more plausible to define the will as a cluster of conative, cognitive, affective, and physical capacities extending from an initial desire to act to the performance of the action. These capacities collectively provide an agent with control of her thought and behavior.The mental capacities necessary for self-control are mediated by neuronal processes involving re-entrant loops consisting of the subcortical basal ganglia and thalamus, limbic structures such as the amygdala, and prefrontal, anterior cingulate, and parietal cortices.3 Component structures of the basal ganglia, such as the striatum, primarily regulate motor control but also some of the conative, cognitive, and affective processes necessary for motivation, attention, and planning. The thalamus relays information from the sensory cortex to the amygdala and higher-brain regions. It also plays a critical role in conscious arousal and awareness through its projections to the cortex. The amygdala mediates emotion, and the anterior cingulate is crucial for empathy and the perception and resolution of conflict. Prefrontal areas of the cerebral cortex mediate practical and moral reasoning. Interacting cortical, limbic, and subcortical pathways provide the neurobiological underpinning of the mental and physical capacities necessary to reason, decide, and act. Still, the desires, beliefs, emotions, and intentions that constitute the will are not reducible to physical processes in the brain because these processes cannot capture the phenomenology, or subjective experience, of having these mental states in ordered or disordered forms.All persons with the capacity for conscious awareness have a will. But they possess and exercise it to varying degrees. The extent to which the will is free depends on whether the neurobiological processes that sustain the requisite mental and physical capacities for deliberation, choice, and action are functional or dysfunctional. This can be a matter of degree as well. Some of these capacities may be intact, while one or more may be impaired, which can diminish the will by constraining or compelling action. A person with Parkinson's disease may retain conative, cognitive, and affective capacities necessary to form plans of action but have diminished physical capacity to execute these plans because of impaired motor control. One with schizophrenia who experiences delusions may be sufficiently motivated and physically able to act but impaired in the cognitive capacity to have appropriate beliefs and respond to reasons for or against actions. A person with major depression may retain cognitive and physical capacities, but anhedonia (inability to experience pleasure from previously pleasurable activities), avolition (lack of motivation to pursue meaningful goals), and low mood may impair his conative and affective capacity to motivate himself to act. Even when there is no neurological or psychiatric abnormality, we do not always completely control our behavior because of unconscious neural processes involved in the performance of our actions.Drugs such as dopamine agonists or deep-brain stimulation (DBS) may restore motor control in Parkinson's disease by compensating for depletion of dopaminergic neurons in the substantia nigra region of the basal ganglia. DBS for this disease involves implanting and stimulating electrodes in this same brain region to modulate overactive or underactive neural circuits regulating movement. Antipsychotic medication may resolve the delusions and restore the cognitive functions regulating the schizophrenic's beliefs to normal or near-normal levels. …

Complementary Function and Integrated Wiring of the Evolutionarily DistinctDrosophilaOlfactory Subsystems

To sense myriad environmental odors, animals have evolved multiple, large families of divergent olfactory receptors. How and why distinct receptor repertoires and their associated circuits are functionally and anatomically integrated is essentially unknown. We have addressed these questions through comprehensive comparative analysis of the Drosophila olfactory subsystems that express the ionotropic receptors (IRs) and odorant receptors (ORs). We identify ligands for most IR neuron classes, revealing their specificity for select amines and acids, which complements the broader tuning of ORs for esters and alcohols. IR and OR sensory neurons exhibit glomerular convergence in segregated, although interconnected, zones of the primary olfactory center, but these circuits are extensively interdigitated in higher brain regions. Consistently, behavioral responses to odors arise from an interplay between IR- and OR-dependent pathways. We integrate knowledge on the different phylogenetic and developmental properties of these receptors and circuits to propose models for the functional contributions and evolution of these distinct olfactory subsystems.

Cross-species affective neuroscience decoding of the primal affective experiences of humans and related animals.

BackgroundThe issue of whether other animals have internally felt experiences has vexed animal behavioral science since its inception. Although most investigators remain agnostic on such contentious issues, there is now abundant experimental evidence indicating that all mammals have negatively and positively-valenced emotional networks concentrated in homologous brain regions that mediate affective experiences when animals are emotionally aroused. That is what the neuroscientific evidence indicates.Principal FindingsThe relevant lines of evidence are as follows: 1) It is easy to elicit powerful unconditioned emotional responses using localized electrical stimulation of the brain (ESB); these effects are concentrated in ancient subcortical brain regions. Seven types of emotional arousals have been described; using a special capitalized nomenclature for such primary process emotional systems, they are SEEKING, RAGE, FEAR, LUST, CARE, PANIC/GRIEF and PLAY. 2) These brain circuits are situated in homologous subcortical brain regions in all vertebrates tested. Thus, if one activates FEAR arousal circuits in rats, cats or primates, all exhibit similar fear responses. 3) All primary-process emotional-instinctual urges, even ones as complex as social PLAY, remain intact after radical neo-decortication early in life; thus, the neocortex is not essential for the generation of primary-process emotionality. 4) Using diverse measures, one can demonstrate that animals like and dislike ESB of brain regions that evoke unconditioned instinctual emotional behaviors: Such ESBs can serve as ‘rewards’ and ‘punishments’ in diverse approach and escape/avoidance learning tasks. 5) Comparable ESB of human brains yield comparable affective experiences. Thus, robust evidence indicates that raw primary-process (i.e., instinctual, unconditioned) emotional behaviors and feelings emanate from homologous brain functions in all mammals (see Appendix S1), which are regulated by higher brain regions. Such findings suggest nested-hierarchies of BrainMind affective processing, with primal emotional functions being foundational for secondary-process learning and memory mechanisms, which interface with tertiary-process cognitive-thoughtful functions of the BrainMind.

Olfactory Coding: Giant Inhibitory Neuron Governs Sparse Odor Codes

Electrophysiological investigations in locusts have revealed that the sparseness of odor representations, in the brain region expected to mediate olfactory learning, is shaped by a unique inhibitory neuron.

Expression of early growth response protein 1 in vasopressin neurones of the rat anterior olfactory nucleus following social odour exposure

The anterior olfactory nucleus (AON), a component of the main olfactory system, is a cortical region that processes olfactory information and acts as a relay between the main olfactory bulbs and higher brain regions such as the piriform cortex. Utilizing a transgenic rat in which an enhanced green fluorescent protein reporter gene is expressed in vasopressin neurones (eGFP-vasopressin), we have discovered a population of vasopressin neurones in the AON. These vasopressin neurones co-express vasopressin V1 receptors. They also co-express GABA and calbinin-D28k indicating that they are neurochemically different from the newly described vasopressin neurons in the main olfactory bulb. We utilized the immediate early gene product, early growth response protein 1 (Egr-1), to examine the functional role of these vasopressin neurons in processing social and non-social odours in the AON. Exposure of adult rats to a conspecific juvenile or a heterospecific predator odour leads to increases in Egr-1 expression in the AON in a subregion specific manner. However, only exposure to a juvenile increases Egr-1 expression in AON vasopressin neurons. These data suggest that vasopressin neurones in the AON may be selectively involved in the coding of social odour information.

Dependence of brain DTI maps of fractional anisotropy and mean diffusivity on the number of diffusion weighting directions

The rotational variance dependence of diffusion tensor imaging (DTI) derived parameters on the number of diffusion weighting directions (N) has been investigated by several Monte Carlo simulation studies. However, the dependence of fractional anisotropy (FA) and mean diffusivity (MD) maps on N, in terms of accuracy and contrast between different anatomical structures, has not been assessed in detail. This experimental study further investigated in vivo the effect of the number of diffusion weighting directions on DTI maps of FA and MD. Human brain FA and MD maps of six healthy subjects were acquired at 1.5T with varying N (6, 11, 19, 27, 55). Then, FA and MD mean values in high (FAH,MDH) and low (FAL,MDL) anisotropy segmented brain regions were measured. Moreover, the contrast‐to‐signal variance ratio (CVRFA,CVRMD) between the main white matter and the surrounding regions was calculated. Analysis of variance showed that FAL,FAH and CVRFA significantly (p<0.05) depend on N. In particular, FAL decreased (6%–11%) with N, whereas FAH (1.6%–2.5%) and CVRFA (4%–6.5%) increased with N.MDL,MDH and CVRMD did not significantly (p>0.05) depend on N. Unlike MD values, FA values significantly vary with N. It is noteworthy that the observed variation is opposite in low and high anisotropic regions. In clinical studies, the effect of N may represent a confounding variable for anisotropy measurements and the employment of DTI acquisition schemes with high N(>20) allows an increased CVR and a better visualization of white matter structures in FA maps.PACS number: 87.61.Tg, 82.56.Lz

The emotional motor system and micturition control

Micturition is, similar to all other movements of the body, the result of activation of the motor system in the central nervous system. This review explains how the brain and brainstem control micturition. The basic reflex system begins with a distinct cell group called Gert's Nucleus (GN) in the sacral cord. GN receives information about bladder contents via A-delta fibers from the bladder and bladder sphincter and relays this information to the central part of the midbrain periaqueductal gray (PAG), but not to the thalamus. The PAG, in turn, in case of substantial bladder filling, excites the pontine micturition center (PMC), which cell group, via its long descending pathways to the sacral cord, induces micturition. Higher brain regions in prefrontal cortex and limbic system, by means of its projections to the PAG are able to interrupt this basic reflex system. It allows the individual to postpone micturition until time and place are appropriate. Lesions in the pathways from prefrontal cortex and limbic system to the PAG probably cause urge-incontinence in the elderly.

Long-term neurodevelopmental disorders in mice with apneas during prematurity

Epidemological evidence points towards a link between the severity of apneas of prematurity and developmental disorders. However, the causality in this relation has not yet been established. In this study, we made use of a genetic mouse model (Phox2b) that is characterized by an increased apnea time (approximately 6-fold at age P5 compared to wildtype littermates) during normoxia. These breathing problems are, however, confined to 2 to 5 days of postnatal age (≈ severe to moderate prematurity in humans) and mice survive normally without ventilatory support. Furthermore, Phox2b is not expressed in higher brain areas, thus excluding direct effects of the mutation on cognitive development. The described phenotype is particularly useful in light of our interest in the consequences of apneas of prematurity on cognitive functioning. To address this issue, we conducted a behavioural test battery in Phox2b adult mice. We conducted a behavioural study in a genotype (Phox2b heterozygote (HZ) vs wildtype (WT))- and gender-mixed group of adult mice ( N =37). Neuromotor performance (rotarod, grip strength) and cage activity were tested, as well as anxiety and exploration (open field, social exploration and elevated plus maze), and learning and memory (passive avoidance learning and Morris water maze). Phox2b HZ mice showed no differences in weight, nor alterations in neuromotor performance or activity level compared to controls. During the open field and social exploration tests Phox2b HZ exhibited significantly less exploratory behaviour than WT. This behavioural observation was also confirmed in the elevated plus maze. Passive avoidance learning was abolished in a subgroup of Phox2b heterozygotes. Moreover, we found that Phox2b HZ mice were slower to acquire learning in the Morris water maze and displayed small but significant memory deficits in both Morris water maze protocols we applied. In this study, we investigated the long term effects of postnatal apneas by conducting a behavioural study on adult Phox2b mice. We found important deficits in exploratory behaviour, and learning and memory functioning in Phox2b HZ. Since Phox2b is not expressed in higher brain regions which are involved in behavioural tests, these differences are likely to arise from neonatal apneas.