Higher-order Centers Research Articles

Temporal Patterns of Individual Neuronal Firing in Rat Dorsal Column Nuclei Provide Information Required for Somatosensory Discrimination.

A wealth of mechanical information from the body generates various forms of sensory experience during touch or kinesthesia. Dorsal column nuclei (DCN) in the medulla are the first relay station for somatosensory inputs from peripheral receptors. These nuclei integrate somatosensory information and send the output to higher-order centers; therefore, investigating the firing patterns of DCN neurons should elucidate coding principles within the somatosensory system. In this study, we quantified the firing patterns of DCN neurons and examined whether the firing patterns of particular neurons are altered when moving tactile stimuli are applied in different directions. The activities of 17 neurons in the DCN of anesthetized rats were selected and their firing patterns were analyzed using LvR, which refers to the local variation of intervals of action potentials (i.e., the cross-correlation between consecutive intervals of action potentials) compensated by the refractoriness constant, R. The LvR of the 17 neurons ranged widely from 0.35 to 2.28. Of the 17 neurons, 12 responded to hair deflection (hair neurons), whereas five responded specifically to movement of forelimb joints. In 11 of 12 hair neurons, moving stimuli were applied in two to four different directions, which yielded 25 pairs of comparisons. Of these, 14 pairs (56%) showed significant differences in LvR. Among these 14 pairs, the range of LvR fluctuation was 0.13 ± 0.06 (mean ± standard deviation) and its effect size (Cohen's d) was 0.6 ± 0.2. These results suggest that the firing pattern of individual DCN neurons may contribute to somatosensory discrimination.

Gene expression profiles and neural activities of Kenyon cell subtypes in the honeybee brain: identification of novel 'middle-type' Kenyon cells.

In the honeybee (Apis mellifera L.), it has long been thought that the mushroom bodies, a higher-order center in the insect brain, comprise three distinct subtypes of intrinsic neurons called Kenyon cells. In class-I large-type Kenyon cells and class-I small-type Kenyon cells, the somata are localized at the edges and in the inner core of the mushroom body calyces, respectively. In class-II Kenyon cells, the somata are localized at the outer surface of the mushroom body calyces. The gene expression profiles of the large- and small-type Kenyon cells are distinct, suggesting that each exhibits distinct cellular characteristics. We recently identified a novel gene, mKast (middle-type Kenyon cell-preferential arrestin-related gene-1), which has a distinctive expression pattern in the Kenyon cells. Detailed expression analyses of mKast led to the discovery of novel ‘middle-type’ Kenyon cells characterized by their preferential mKast-expression in the mushroom bodies. The somata of the middle-type Kenyon cells are localized between the large- and small-type Kenyon cells, and the size of the middle-type Kenyon cell somata is intermediate between that of large- and small-type Kenyon cells. Middle-type Kenyon cells appear to differentiate from the large- and/or small-type Kenyon cell lineage(s). Neural activity mapping using an immediate early gene, kakusei, suggests that the small-type and some middle-type Kenyon cells are prominently active in the forager brain, suggesting a potential role in processing information during foraging flight. Our findings indicate that honeybee mushroom bodies in fact comprise four types of Kenyon cells with different molecular and cellular characteristics: the previously known class-I large- and small-type Kenyon cells, class-II Kenyon cells, and the newly identified middle-type Kenyon cells described in this review. As the cellular characteristics of the middle-type Kenyon cells are distinct from those of the large- and small-type Kenyon cells, their careful discrimination will be required in future studies of honeybee Kenyon cell subtypes. In this review, we summarize recent progress in analyzing the gene expression profiles and neural activities of the honeybee Kenyon cell subtypes, and discuss possible roles of each Kenyon cell subtype in the honeybee brain.

Parallel Olfactory Processing in the Honey Bee Brain: Odor Learning and Generalization under Selective Lesion of a Projection Neuron Tract.

The function of parallel neural processing is a fundamental problem in Neuroscience, as it is found across sensory modalities and evolutionary lineages, from insects to humans. Recently, parallel processing has attracted increased attention in the olfactory domain, with the demonstration in both insects and mammals that different populations of second-order neurons encode and/or process odorant information differently. Among insects, Hymenoptera present a striking olfactory system with a clear neural dichotomy from the periphery to higher-order centers, based on two main tracts of second-order (projection) neurons: the medial and lateral antennal lobe tracts (m-ALT and l-ALT). To unravel the functional role of these two pathways, we combined specific lesions of the m-ALT tract with behavioral experiments, using the classical conditioning of the proboscis extension response (PER conditioning). Lesioned and intact bees had to learn to associate an odorant (1-nonanol) with sucrose. Then the bees were subjected to a generalization procedure with a range of odorants differing in terms of their carbon chain length or functional group. We show that m-ALT lesion strongly affects acquisition of an odor-sucrose association. However, lesioned bees that still learned the association showed a normal gradient of decreasing generalization responses to increasingly dissimilar odorants. Generalization responses could be predicted to some extent by in vivo calcium imaging recordings of l-ALT neurons. The m-ALT pathway therefore seems necessary for normal classical olfactory conditioning performance.

Olfactory Coding in the Honeybee Lateral Horn

Olfactory systems dynamically encode odor information in the nervous system. Insects constitute a well-established model for the study of the neural processes underlying olfactory perception. In insects, odors are detected by sensory neurons located in the antennae, whose axons project to a primary processing center, the antennal lobe. There, the olfactory message is reshaped and further conveyed to higher-order centers, the mushroom bodies and the lateral horn. Previous work has intensively analyzed the principles of olfactory processing in the antennal lobe and in the mushroom bodies. However, how the lateral horn participates in olfactory coding remains comparatively more enigmatic. We studied odor representation at the input to the lateral horn of the honeybee, a social insect that relies on both floral odors for foraging and pheromones for social communication. Using in vivo calcium imaging, we show consistent neural activity in the honeybee lateral horn upon stimulation with both floral volatiles and social pheromones. Recordings reveal odor-specific maps in this brain region as stimulations with the same odorant elicit more similar spatial activity patterns than stimulations with different odorants. Odor-similarity relationships are mostly conserved between antennal lobe and lateral horn, so that odor maps recorded in the lateral horn allow predicting bees' behavioral responses to floral odorants. In addition, a clear segregation of odorants based on pheromone type is found in both structures. The lateral horn thus contains an odor-specific map with distinct representations for the different bee pheromones, a prerequisite for eliciting specific behaviors.

The neural encoding of self-generated and externally applied movement: implications for the perception of self-motion and spatial memory

The vestibular system is vital for maintaining an accurate representation of self-motion. As one moves (or is moved) toward a new place in the environment, signals from the vestibular sensors are relayed to higher-order centers. It is generally assumed the vestibular system provides a veridical representation of head motion to these centers for the perception of self-motion and spatial memory. In support of this idea, evidence from lesion studies suggests that vestibular inputs are required for the directional tuning of head direction cells in the limbic system as well as neurons in areas of multimodal association cortex. However, recent investigations in monkeys and mice challenge the notion that early vestibular pathways encode an absolute representation of head motion. Instead, processing at the first central stage is inherently multimodal. This minireview highlights recent progress that has been made towards understanding how the brain processes and interprets self-motion signals encoded by the vestibular otoliths and semicircular canals during everyday life. The following interrelated questions are considered. What information is available to the higher-order centers that contribute to self-motion perception? How do we distinguish between our own self-generated movements and those of the external world? And lastly, what are the implications of differences in the processing of these active vs. passive movements for spatial memory?

Multisensory integration in early vestibular processing in mice: the encoding of passive vs. active motion

The mouse has become an important model system for studying the cellular basis of learning and coding of heading by the vestibular system. Here we recorded from single neurons in the vestibular nuclei to understand how vestibular pathways encode self-motion under natural conditions, during which proprioceptive and motor-related signals as well as vestibular inputs provide feedback about an animal's movement through the world. We recorded neuronal responses in alert behaving mice focusing on a group of neurons, termed vestibular-only cells, that are known to control posture and project to higher-order centers. We found that the majority (70%, n = 21/30) of neurons were bimodal, in that they responded robustly to passive stimulation of proprioceptors as well as passive stimulation of the vestibular system. Additionally, the linear summation of a given neuron's vestibular and neck sensitivities predicted well its responses when both stimuli were applied simultaneously. In contrast, neuronal responses were suppressed when the same motion was actively generated, with the one striking exception that the activity of bimodal neurons similarly and robustly encoded head on body position in all conditions. Our results show that proprioceptive and motor-related signals are combined with vestibular information at the first central stage of vestibular processing in mice. We suggest that these results have important implications for understanding the multisensory integration underlying accurate postural control and the neural representation of directional heading in the head direction cell network of mice.

The nucleus prepositus predominantly outputs eye movement-related information during passive and active self-motion

Maintaining a constant representation of our heading as we move through the world requires the accurate estimate of spatial orientation. As one turns (or is turned) toward a new heading, signals from the semicircular canals are relayed through the vestibular system to higher-order centers that encode head direction. To date, there is no direct electrophysiological evidence confirming the first relay point of head-motion signals from the vestibular nuclei, but previous anatomical and lesion studies have identified the nucleus prepositus as a likely candidate. Whereas burst-tonic neurons encode only eye-movement signals during head-fixed eye motion and passive vestibular stimulation, these neurons have not been studied during self-generated movements. Here, we specifically address whether burst-tonic neurons encode head motion during active behaviors. Single-unit responses were recorded from the nucleus prepositus of rhesus monkeys and compared for head-restrained and active conditions with comparable eye velocities. We found that neurons consistently encoded eye position and velocity across conditions but did not exhibit significant sensitivity to head position or velocity. Additionally, response sensitivities varied as a function of eye velocity, similar to abducens motoneurons and consistent with their role in gaze control and stabilization. Thus our results demonstrate that the primate nucleus prepositus chiefly encodes eye movement even during active head-movement behaviors, a finding inconsistent with the proposal that this nucleus makes a direct contribution to head-direction cell tuning. Given its ascending projections, however, we speculate that this eye-movement information is integrated with other inputs in establishing higher-order spatial representations.

Differences in parvalbumin and calbindin chemospecificity in the centers of the turtle ascending auditory pathway revealed by double immunofluorescence labeling

Using double immunofluorescence labeling, quantitative ratio between parvalbumin- and calbindin-containing neurons, neurons that co-localize both peptides, as well as the intensity of their immunoreactivities were studied in the brainstem, midbrain and forebrain auditory centers of two chelonian species, Testudo horsfieldi and Emys orbicularis. In the spiral ganglion and first-order cochlear nuclei, highly immunoreactive parvalbumin-containing neurons predominated, and almost all neurons in these nuclei also exhibited weak immunoreactivity to calbindin. The number of strongly calbindin-immunoreactive (-ir) cells increased in the second-order brainstem auditory centers (the laminar cochlear nucleus, superior olivary complex, lateral lemniscal nucleus), and co-localization with parvalbumin in some of them was observed. In the midbrain, a complementary distribution of parvalbumin and calbindin immunoreactivity was found: the central (core) region of the torus semicircularis showed strong parvalbumin immunoreactivity, while the laminar (belt) nucleus was strongly calbindin-ir. In the thalamic nucleus reuniens, almost complete topographic overlapping of the parvalbumin-ir and calbindin-ir neurons was shown in its dorsomedial region (core), with the intensity of immunoreactivity to calbindin being much higher than that to parvalbumin. The predominance of calbindin immunoreactivity in neurons of the dorsomedial region of the nucleus reuniens is correlated with the existence of the dense calbindin-ir terminal field in its projection area in the telencephalon. We conclude that the turtle auditory pathway is chemically heterogeneous with respect to calcium-binding proteins, the predominance of parvalbumin in the brainstem and midbrain centers giving way to that of calbindin in the forebrain centers; the portion of neurons co-localizing both peptides nonlinearly decreases from lower to higher order centers.

Differential coding by two olfactory subsystems in the honeybee brain

Sensory systems use parallel processing to extract and process different features of environmental stimuli. Parallel processing has been studied in the auditory, visual, and somatosensory systems, but equivalent research in the olfactory modality is scarce. The honeybee Apis mellifera is an interesting model for such research as its relatively simple brain contains a dual olfactory system, with a clear neural dichotomy from the periphery to higher-order centers, based on two main neuronal tracts [medial (m) and lateral (l) antenno-protocerebral tract (APT)]. The function of this dual system is as yet unknown, and attributes like odor quality and odor quantity might be separately encoded in these subsystems. We have thus studied olfactory coding at the input of both subsystems, using in vivo calcium imaging. As one of the subsystems (m-APT) has never been imaged before, a novel imaging preparation was developed to this end, and responses to a panel of aliphatic odorants at different concentrations were compared in both subsystems. Our data show a global redundancy of olfactory coding at the input of both subsystems but unravel some specificities for encoding chemical group and carbon chain length of odor molecules.

Differential neural correlates of reciprocal activation and cocontraction control in dorsal and ventral premotor cortices

Efficient control of reciprocal activation and cocontraction of the muscles are critical to perform skillful actions with suitable force and impedance. However, it remains unclear how the brain controls force and impedance while recruiting the same set of muscles as actuators. Does control take place at the single muscle level leading to force and impedance, or are there higher-order centers dedicated to controlling force and impedance? We addressed this question using functional MRI during voluntary isometric wrist contractions with online electromyogram feedback. Comparison of the brain activity between the conditions requiring control of either wrist torque or cocontraction demonstrates that blood oxygen level-dependent activity in the caudo-dorsal premotor cortex (PMd) correlates well with torque, whereas the activity in the ventral premotor cortex (PMv) correlates well with the level of cocontraction. This suggests distinct roles of the PMd and PMv in the voluntary control of reciprocal activation and cocontraction of muscles, respectively.

Information transmission and detection thresholds in the vestibular nuclei: single neurons vs. population encoding

Understanding how sensory neurons transmit information about relevant stimuli remains a major goal in neuroscience. Of particular relevance are the roles of neural variability and spike timing in neural coding. Peripheral vestibular afferents display differential variability that is correlated with the importance of spike timing; regular afferents display little variability and use a timing code to transmit information about sensory input. Irregular afferents, conversely, display greater variability and instead use a rate code. We studied how central neurons within the vestibular nuclei integrate information from both afferent classes by recording from a group of neurons termed vestibular only (VO) that are known to make contributions to vestibulospinal reflexes and project to higher-order centers. We found that, although individual central neurons had sensitivities that were greater than or equal to those of individual afferents, they transmitted less information. In addition, their velocity detection thresholds were significantly greater than those of individual afferents. This is because VO neurons display greater variability, which is detrimental to information transmission and signal detection. Combining activities from multiple VO neurons increased information transmission. However, the information rates were still much lower than those of equivalent afferent populations. Furthermore, combining responses from multiple VO neurons led to lower velocity detection threshold values approaching those measured from behavior (∼ 2.5 vs. 0.5-1°/s). Our results suggest that the detailed time course of vestibular stimuli encoded by afferents is not transmitted by VO neurons. Instead, they suggest that higher vestibular pathways must integrate information from central vestibular neuron populations to give rise to behaviorally observed detection thresholds.

Core-and-belt organisation of the mesencephalic and forebrain auditory centres in turtles: Expression of calcium-binding proteins and metabolic activity

The distribution of immunoreactivity to the calcium-binding proteins parvalbumin, calbindin and calretinin and of cytochrome oxidase activity was studied in the mesencephalic (torus semicircularis), thalamic (nucleus reuniens) and telencephalic (ventromedial part of the anterior dorsal ventricular ridge) auditory centres of two chelonian species Emys orbicularis and Testudo horsfieldi. In the torus semicircularis, the central nucleus (core) showed intense parvalbumin immunoreactivity and high cytochrome oxidase activity, whereas the laminar nucleus (belt) showed low cytochrome oxidase activity and dense calbindin/calretinin immunoreactivity. Within the central nucleus, the central and peripheral areas could be distinguished by a higher density of parvalbumin immunoreactivity and cytochrome oxidase activity in the core than in the peripheral area. In the nucleus reuniens, the dorsal and ventromedial (core) regions showed high cytochrome oxidase activity and immunoreactivity to all three calcium-binding proteins, while its ventrolateral part (belt) was weakly immunoreactive and showed lower cytochrome oxidase activity. In the telencephalic auditory centre, on the other hand, no particular region differed in either immunoreactivity or cytochrome oxidase activity. Our findings provide additional arguments in favour of the hypothesis of a core-and-belt organisation of the auditory sensory centres in non-mammalian amniotes though this organisation is less evident in higher order centres. The data are discussed in terms of the evolution of the auditory system in amniotes.

Human brain activation associated with cough and cough suppression

Supramedullary brain regions may contribute to control of cough by facilitating or inhibiting brainstem reflex pathways. Using functional brain imaging, we put this putative model to the test. Blood oxygen level‐dependent (BOLD) contrast images were acquired from 15 healthy subjects after inhaling saline, inhaling capsaicin without cough, inhaling capsaicin with cough, and voluntary cough after inhaling saline. BOLD signals were analysed to identify changes associated with cough, capsaicin stimulation and their interactions. Contrary to the hypothesised effect, the positive interaction of cough and capsaicin stimulation did not implicate brain activation uniquely associated with evoked cough. However, the negative interaction revealed brain activations that may be requisite for the initiation of voluntary cough and suppression of evoked cough (inferior frontal gyrus, SMA, cingulate cortex) as well as ongoing sensations associated with capsaicin in the airways (insula, orbitofrontal cortex)(P<0.05). These data show that voluntary cough and suppression of evoked cough are associated with brain activation in excess of that associated with evoked cough. This outcome suggests that evoked cough is a default motor pattern that does not require active facilitation by higher order centres, but is under higher order inhibitory influences.Funding: NHMRC Australia #454776, #566734

An identified serotonergic neuron regulates adult neurogenesis in the crustacean brain

New neurons are born and integrated into functional circuits in the brains of many adult organisms. In virtually all of these systems, serotonin is a potent regulator of neuronal proliferation. Specific neural pathways underlying these serotonergic influences have not, however, been identified and manipulated. The goal of this study was to test whether adult neurogenesis in the crustacean brain is influenced by electrical activity in the serotonergic dorsal giant neurons (DGNs) innervating the primary olfactory processing areas, the olfactory lobes, and higher order centers, the accessory lobes. Adult-born neurons occur in two interneuronal cell clusters that are part of the olfactory pathway. This study demonstrates that neurogenesis also continues in these areas in a dissected, perfused brain preparation, although the rate of neuronal production is lower than in brains from intact same-sized animals. Inclusion of 10(-9) M serotonin in the perfusate delivered to the dissected brain preparation restores the rate of neurogenesis to in vivo levels. Although subthreshold stimulation of the DGN does not significantly alter the rate of neurogenesis, electrical activation of a single DGN results in significant increases in neurogenesis in Cluster 10 on the same side of the brain, when compared with levels on the contralateral, unstimulated side. Measurements of serotonin levels in the perfusate using high-performance liquid chromatography established that serotonin levels are elevated about 10-fold during DGN stimulation, confirming that serotonin is released during DGN activity. This is the first identified neural pathway through which adult neurogenesis has been directly manipulated.

Glutamate and nitric oxide modulate ERK and CREB phosphorylation in the avian retina: evidence for direct signaling from neurons to Müller glial cells

Glutamate signaling in the mature retinal tissue is very important for accurate sensory decoding by retinal neurons and orchestrates the fine-tuned output from the retina to higher-order centers at the cerebral cortex. In this study, we show that glutamate induces a rapid extracellular-regulated kinase and cAMP-responsive element binding protein (CREB) phosphorylation in cultured developing retinal neurons. This process is reliant on alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors and nitric oxide (NO) signaling and independent of NMDA receptors activation, as it is blocked by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate antagonists as well as inhibiting NO synthase with NG-nitro-L-arginine methyl ester but not by the NMDA channel blocker dizocilpine maleate. The effect of NO on extracellular-regulated kinase and CREB is mediated by the classical NO/soluble guanylyl cyclase/protein kinase G pathways as it is inhibited by the soluble guanylyl cyclase blocker 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one and the protein kinase G inhibitor KT5823, respectively. Immunocytochemical data suggest that increased CREB phosphorylation in response to glutamate occurs in glial cell nuclei. We also have supporting evidence suggesting that neuronally produced NO directly reaches the glial cells and stimulates CREB phosphorylation. Hence, the results indicate the importance of neuronal-glial communication and glutamate/NO/CREB linkage during retinal development.

Editor's remarks: Chemotopic odorant coding in a mammalian olfactory system, Johnson et al., J Comp Neurol 503:1–34

Editor's remarks: Chemotopic odorant coding in a mammalian olfactory system, Johnson et al., J Comp Neurol 503:1–34

Apraxia, agnosias, and higher visual function abnormalities

Cognitive neurology deals mainly with disorders of memory (for example, is the patient’s poor memory due to early dementia or to anxiety/depression?) or language (as in stroke). It should be...

The role of district capitals in regional development: Linking small towns, rural–urban linkages and decentralisation in Ghana

Ghana's decentralisation programme involves the strengthening of district capitals (defined in this paper as small towns) as focal points for the socio-economic development of districts. Few studies have, however, been done on the role of district capitals and the linkages between these centres and their hinterlands as a basis for evaluating the effectiveness of the strategy. This paper provides a conceptualised and analytical model for examining the role of district capitals and rural–urban linkages in regional development in Ghana. The model is operationalised using two district capitals in the central region as a case study. The paper identifies four critical factors in operationalising the model: small towns' production and service functions; proximity and accessibility to higher-order centres; national macro-economic policies; and the impact of Ghana's decentralisation programme. It concludes that the desired goals of the strategy can be achieved by a genuine decentralisation policy and supportive di...

Central Olfactory Pathway in Response to Olfactory Stimulation in Rats Detected by Magnetic Resonance Imaging

The olfactory system is known to have important roles in neuroendocrine regulation, emotional responses, reproductive/maternal functions, aggression, food selection and the recognition of conspecifics, predators and prey, etc. (Shipley et al., 1995). Especially in the case of food/fluid selection and intake, olfaction plays very important roles in combination with taste and texture. The pathway of the olfactory system has a unique characteristic relative to other sensory systems in that the signals go directly to the primary sensory cortical areas and limbic system without involvement of the brain stem. The limbic system is related to emotion, learning and memory. Therefore, odors can affect the preference for food and its memory. So far, there is little direct evidence demonstrating the activation of higher-order olfactory centers during olfactory stimulation except for activation in the olfactory bulb (OB) (Yang et al., 1998; Xu et al., 2000, 2003). In the first part of the present study (experiment I), brain activation areas in response to olfactory stimulation were investigated in anesthetized rats using functional magnetic resonance imaging (fMRI). In the second part of the present study (experiment II), neural projections in higher-order olfactory centers, especially projections from several olfactory centers to the medial frontal cortex (MFC), were investigated using manganese-enhanced MRI (MEMRI), a newly developed in vivo neural tracing technique (Pautler et al., 1998, 2003; Van der Linden et al., 2002). The first part of the study suggested that the MFC, which is a part of the limbic system and not considered one of the olfactory centers (Shipley et al., 1995), responded well to olfactory stimulation to a similar extent and with response patterns similar to the primary olfactory cortical areas, i.e. the piriform cortex, olfactory tubercle, etc. (Kondoh et al., 2002, 2003). Injection of Mn2+, a biological calcium analogue and paramagnetic tract tracing agent, allows highlighting specific brain areas that are active in MEMRI.

Erreichbarkeiten und Einwohnerpotenziale Zentraler Orte

In the course of up-dating the State Development Plan for the federal state of Thuringia, and against the backdrop of dwindling populations and improvements in accessibility, the decision was taken to overhaul the “central-place” concept introduced in 1993. Drawing on accessibility analyses based on private-car use, the future population potentials of so-called “higher-order centres” have been recalculated in order to gauge the long-term significance of such centres for spatial planning within the state. In the light of current levels of infrastructure endowment and capacity utilisation, the authors are able to proceed to formulating recommendations for a future system of “central places” which strives to mediate between blanket supply and economic viability. The current and anticipated shortcomings thus revealed in respect of accessibility provide important pointers toward the types of supplementary structure-policy measures which the state will need to adopt in the future.