RESUMEN
The hippocampus has a major role in encoding and consolidating long-term memories, and undergoes plastic changes during sleep1. These changes require precise homeostatic control by subcortical neuromodulatory structures2. The underlying mechanisms of this phenomenon, however, remain unknown. Here, using multi-structure recordings in macaque monkeys, we show that the brainstem transiently modulates hippocampal network events through phasic pontine waves known as pontogeniculooccipital waves (PGO waves). Two physiologically distinct types of PGO wave appear to occur sequentially, selectively influencing high-frequency ripples and low-frequency theta events, respectively. The two types of PGO wave are associated with opposite hippocampal spike-field coupling, prompting periods of high neural synchrony of neural populations during periods of ripple and theta instances. The coupling between PGO waves and ripples, classically associated with distinct sleep stages, supports the notion that a global coordination mechanism of hippocampal sleep dynamics by cholinergic pontine transients may promote systems and synaptic memory consolidation as well as synaptic homeostasis.
Asunto(s)
Cuerpos Geniculados/fisiología , Hipocampo/fisiología , Lóbulo Occipital/fisiología , Puente/fisiología , Sueño/fisiología , Ritmo Teta/fisiología , Animales , Emparejamiento Cromosómico/fisiología , Femenino , Homeostasis , Macaca/fisiología , Consolidación de la Memoria/fisiología , Plasticidad Neuronal , Fases del Sueño/fisiologíaRESUMEN
Digitized neuroanatomical atlases that can be overlaid onto functional data are crucial for localizing brain structures and analyzing functional networks identified by neuroimaging techniques. To aid in functional and structural data analysis, we have created a comprehensive parcellation of the rhesus macaque subcortex using a high-resolution ex vivo structural imaging scan. This anatomical scan and its parcellation were warped to the updated NIMH Macaque Template (NMT v2), an in vivo population template, where the parcellation was refined to produce the Subcortical Atlas of the Rhesus Macaque (SARM) with 210 primary regions-of-interest (ROIs). The subcortical parcellation and nomenclature reflect those of the 4th edition of the Rhesus Monkey Brain in Stereotaxic Coordinates (Paxinos et al., in preparation), rather than proposing yet another novel atlas. The primary ROIs are organized across six spatial hierarchical scales from small, fine-grained ROIs to broader composites of multiple ROIs, making the SARM suitable for analysis at different resolutions and allowing broader labeling of functional signals when more accurate localization is not possible. As an example application of this atlas, we have included a functional localizer for the dorsal lateral geniculate (DLG) nucleus in three macaques using a visual flickering checkerboard stimulus, identifying and quantifying significant fMRI activation in this atlas region. The SARM has been made openly available to the neuroimaging community and can easily be used with common MRI data processing software, such as AFNI, where the atlas has been embedded into the software alongside cortical macaque atlases.
Asunto(s)
Atlas como Asunto , Encéfalo/anatomía & histología , Encéfalo/fisiología , Macaca mulatta/anatomía & histología , Macaca mulatta/fisiología , Neuroimagen , Animales , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
Neuroimaging non-human primates (NHPs) is a growing, yet highly specialized field of neuroscience. Resources that were primarily developed for human neuroimaging often need to be significantly adapted for use with NHPs or other animals, which has led to an abundance of custom, in-house solutions. In recent years, the global NHP neuroimaging community has made significant efforts to transform the field towards more open and collaborative practices. Here we present the PRIMatE Resource Exchange (PRIME-RE), a new collaborative online platform for NHP neuroimaging. PRIME-RE is a dynamic community-driven hub for the exchange of practical knowledge, specialized analytical tools, and open data repositories, specifically related to NHP neuroimaging. PRIME-RE caters to both researchers and developers who are either new to the field, looking to stay abreast of the latest developments, or seeking to collaboratively advance the field .
Asunto(s)
Acceso a la Información , Neuroimagen/métodos , Sistemas en Línea , Primates/anatomía & histología , Primates/fisiología , AnimalesRESUMEN
The insula has been classically divided into broad granular, dysgranular, and agranular architectonic sectors. We previously proposed a novel partition, dividing each sector into four to seven sharply delimited architectonic areas, with the dysgranular areas being possibly further subdivided into subtle horizontal partitions or "stripes." In architectonics, discrete subparcellations are prone to subjective variability and need being supported with additional neuroanatomical methods. Here, using a secondary analysis of indirect connectional data in the rhesus macaque monkey, we examined the spatial relationship between the dysgranular architectonic stripes and tract-tracing labeling patterns produced in the insula with injections of neuronal tracers in other cortical regions. The injections consistently produced sharply delimited patches of anterograde and/or retrograde labeling, which formed stripes across consecutive coronal sections of the insula. While the overall pattern of labeling on individual coronal sections varied with the injection site, the boundaries of the patches consistently coincided with architectonic boundaries on an adjacent cyto- (Nissl) and/or myelo- (Gallyas) architectonic section. This overlap supports the existence of a fine dysgranular stripe-like partition of the primate insula, with possibly major implications for interoceptive processing in primates including humans. The modular organization of the insula could underlie a serial stream of integration from a dorsal primary interoceptive cortex toward progressively more ventral egocentric "self-agency" and allocentric "social" dysgranular processing units.
Asunto(s)
Corteza Cerebral , Corteza Insular , Animales , Humanos , Macaca mulatta , NeuronasRESUMEN
As science and technology evolve, there is an increasing need for promotion of international scientific exchange. Collaborations, while offering substantial opportunities for scientists and benefit to society, also present challenges for those working with animal models, such as non-human primates (NHPs). Diversity in regulation of animal research is sometimes mistaken for the absence of common international welfare standards. Here, the ethical and regulatory protocols for 13 countries that have guidelines in place for biomedical research involving NHPs were assessed with a focus on neuroscience. Review of the variability and similarity in trans-national NHP welfare regulations extended to countries in Asia, Europe and North America. A tabulated resource was established to advance solution-oriented discussions and scientific collaborations across borders. Our aim is to better inform the public and other stakeholders. Through cooperative efforts to identify and analyze information with reference to evidence-based discussion, the proposed key ingredients may help to shape and support a more informed, open framework. This framework and resource can be expanded further for biomedical research in other countries.
RESUMEN
We examined the applicability of manganese-enhanced MRI (MEMRI) to the in vivo tracing of diffuse neuromodulatory projections by means of simultaneous iontophoretic injections of an extremely low, non-toxic concentration of MnCl(2) (10mM) and fluorescent dextran in the locus coeruleus (LC) in the rat. We validated the use of the iontophoretic injection by reproducing previously reported results from pressure injections of MnCl(2) in primary somatosensory cortex. Twenty fourhours after injection in LC, Mn(2+) labeling was detected in major cortical and subcortical targets of LC projections including predominantly ipsilateral primary motor and somatosensory cortices, hippocampus and amygdala. Although the injections were in most cases centered in the core of LC, the pattern of Mn(2+) labeling greatly varied across rats. In addition, despite a certain degree of overlap of the labeling obtained with both MEMRI and classical tracing, MEMRI tracing consistently failed to reliably label not only several minor but also major targets of LC, notably the thalamus. The lack of Mn(2+) labeling in thalamus possibly reflected a weaker functional connectivity within coeruleothalamic projections that could not be predicted by anatomical tracing. Inversely, a number of brain regions, particularly contralateral motor cortex, that were not or only sparsely labeled with fluorescent dextran were strongly labeled by Mn(2+). This discrepancy could be partly due to both the activity-dependent and transsynaptic nature of Mn(2+) transport. The overall labeling produced using MEMRI with iontophoretic injections in LC indicates that the Mn(2+) imaging of highly diffuse projections is in principle feasible. However, the labeling pattern of each individual case needs to be carefully interpreted particularly before submitting data for group analysis or in the case of longitudinal examination of discrete changes in functional connectivity under various physiological or behavioral conditions.
Asunto(s)
Neuronas Adrenérgicas , Mapeo Encefálico/métodos , Corteza Cerebral/anatomía & histología , Cloruros , Locus Coeruleus/anatomía & histología , Imagen por Resonancia Magnética/métodos , Compuestos de Manganeso , Animales , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Macroscopic taste processing connectivity was investigated using functional magnetic resonance imaging during the presentation of sour, salty, and sweet tastants in anesthetized macaque monkeys. This examination of taste processing affords the opportunity to study the interactions between sensory regions, central integrators, and effector areas. Here, 58 brain regions associated with gustatory processing in primates were aggregated, collectively forming the gustatory connectome. Regional regression coefficients (or ß-series) obtained during taste stimulation were correlated to infer functional connectivity. This connectivity was then evaluated by assessing its laterality, modularity and centrality. Our results indicate significant correlations between same region pairs across hemispheres in a bilaterally interconnected scheme for taste processing throughout the gustatory connectome. Using unbiased community detection, three bilateral sub-networks were detected within the graph of the connectome. This analysis revealed clustering of 16 medial cortical structures, 24 lateral structures, and 18 subcortical structures. Across the three sub-networks, a similar pattern was observed in the differential processing of taste qualities. In all cases, the amplitude of the response was greatest for sweet, but the network connectivity was strongest for sour and salty tastants. The importance of each region in taste processing was computed using node centrality measures within the connectome graph, showing centrality to be correlated across hemispheres and, to a smaller extent, region volume. Connectome hubs exhibited varying degrees of centrality with a prominent leftward increase in insular cortex centrality. Taken together, these criteria illustrate quantifiable characteristics of the macaque monkey gustatory connectome and its organization as a tri-modular network, which may reflect the general medial-lateral-subcortical organization of salience and interoception processing networks.
RESUMEN
BACKGROUND: Transbronchial lung forceps biopsy (TBLF) is of limited value for the diagnosis of interstitial lung disease (ILD). However, in cases with predominantly peribronchial pathology, such as sarcoidosis, TBLF is considered to be diagnostic in most cases. The present study examines whether transbronchial lung cryobiopsy (TBLC) is superior to TBLF in terms of diagnostic yield in cases of sarcoidosis. METHODS: In this post hoc analysis of a prospective, randomized, controlled, multicentre study, 359 patients with ILD requiring diagnostic bronchoscopic tissue sampling were included. TBLF and TBLC were both used for each patient in a randomized order. Histological assessment was undertaken on each biopsy and determined whether sarcoid was a consideration. RESULTS: A histological diagnosis of sarcoidosis was established in 17 of 272 cases for which histopathology was available. In 6 out of 17 patients, compatible findings were seen with both TBLC and TBLF. In 10 patients, where the diagnosis of sarcoidosis was confirmed by TBLC, TBLF did not provide a diagnosis. In one patient, TBLF but not TBLC confirmed the diagnosis of sarcoidosis. CONCLUSIONS: In this post hoc analysis, the histological diagnosis of sarcoidosis was made significantly more often by TBLC than by TBLF. As in other idiopathic interstitial pneumonias (IIPs), the use of TBLC should be considered when sarcoidosis is suspected.
RESUMEN
Long perceived as a primitive and poorly differentiated brain structure, the primate insular cortex recently emerged as a highly evolved, organized and richly connected cortical hub interfacing bodily states with sensorimotor, environmental, and limbic activities. This insular interface likely substantiates emotional embodiment and has the potential to have a key role in the interoceptive shaping of cognitive processes, including perceptual awareness. In this review, we present a novel working model of the insular cortex, based on an accumulation of neuroanatomical and functional evidence obtained essentially in the macaque monkey. This model proposes that interoceptive afferents that represent the ongoing physiological status of all the organs of the body are first being received in the granular dorsal fundus of the insula or "primary interoceptive cortex," then processed through a series of dysgranular poly-modal "insular stripes," and finally integrated in anterior agranular areas that serve as an additional sensory platform for visceral functions and as an output stage for efferent autonomic regulation. One of the agranular areas hosts the specialized von Economo and Fork neurons, which could provide a decisive evolutionary advantage for the role of the anterior insula in the autonomic and emotional binding inherent to subjective awareness.
Asunto(s)
Dolor , Tálamo , Humanos , Tálamo/diagnóstico por imagen , Percepción del Dolor , Núcleos Talámicos , Mapeo Encefálico , Vías NerviosasRESUMEN
Electrical microstimulation and more recently optogenetics are widely used to map large-scale brain circuits. However, the neuronal specificity achieved with both methods is not well understood. Here we compare cell-targeted optogenetics and electrical microstimulation in the macaque monkey brain to functionally map the koniocellular lateral geniculate nucleus (LGN) projection to primary visual cortex (V1). Selective activation of the LGN konio neurons with CamK-specific optogenetics caused selective electrical current inflow in the supra-granular layers of V1. Electrical microstimulation targeted at LGN konio layers revealed the same supra-granular V1 activation pattern as the one elicited by optogenetics. Taken together, these findings establish a selective koniocellular LGN influence on V1 supra-granular layers, and they indicate comparable capacities of both stimulation methods to isolate thalamo-cortical circuits in the primate brain.
Asunto(s)
Cuerpos Geniculados/fisiología , Neuronas/fisiología , Corteza Visual/fisiología , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Estimulación Eléctrica , Cuerpos Geniculados/metabolismo , Macaca fascicularis , Macaca mulatta , Masculino , Vías Nerviosas/fisiología , OptogenéticaRESUMEN
OBJECTIVE: To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. METHODS: We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. RESULTS: A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. CONCLUSIONS: Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness.
Asunto(s)
Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/fisiopatología , Coma/diagnóstico por imagen , Coma/fisiopatología , Mapeo Encefálico , Tronco Encefálico/fisiología , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología , Vías Nerviosas/fisiopatología , Descanso , Adulto JovenRESUMEN
In addition to exerting genomic actions via nuclear receptors within hours to days, estrogens also regulate neuronal activity much faster (within seconds) by activating neuronal membrane receptors coupled to intracellular second-messenger pathways. To date, the origin of estrogens inducing rapid effects in the brain remains unclear, although it is often ascribed to the gonads. We report here that an acute blockade of the endogenous synthesis of estrogens in the quail spinal dorsal horn markedly reduced, within 1 min, the behavioral responsiveness to a thermal painful stimulus. Similar rapid effects in the opposite direction were induced by estradiol. This finding identifies a new paracrine and nongenomic mechanism for the regulation of pain by estrogens. Such regulation was assumed previously to result only from slow genomic actions of estrogens arising from the ovaries. Also, quite importantly, this finding suggests that the numerous rapid nongenomic effects of estrogens in the CNS could depend on their immediate local production by the enzyme aromatase, independently from the gonads.
Asunto(s)
Estrógenos/biosíntesis , Dolor/etiología , Células del Asta Posterior/enzimología , Animales , Inhibidores de la Aromatasa , Conducta Animal/efectos de los fármacos , Cateterismo , Ventrículos Cerebrales , Coturnix , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/farmacología , Estradiol/farmacología , Estrógenos/fisiología , Calor , Inyecciones Espinales , Cinética , Masculino , Orquiectomía , Dolor/enzimología , Células del Asta Posterior/efectos de los fármacos , Testosterona/farmacología , Triazoles/administración & dosificación , Triazoles/farmacologíaRESUMEN
The distribution of the estrogen synthesizing enzyme (aromatase) in the hindbrain (rhombencephalon and mesencephalon) of male adult quail was investigated by immunocytochemistry. Aromatase-immunoreactive neuronal structures (perikarya and fibers bearing punctate structures) were observed in sensory (trigeminal, solitary tract, vestibular, optic tectum) and integrating (parabrachial, periaqueductal, cerulean, raphe) nuclei. Besides the expression of aromatase in these well-delineated nuclei, dense to scattered networks of immunoreactive fibers were found dispersed throughout the hindbrain and, in particular, in its rostral and dorsal parts. To a lesser extent, they were also present throughout the premotor nuclei of the reticular formation and in various fiber tracts. In contrast, no immunoreactive signal was found in motor nuclei, and in most of the statoacoustic (cerebellum, cochlear, olive, pontine, part of vestibular) nuclei. The expression of aromatase in perikarya and fibers in areas of the adult hindbrain where estrogen receptors have been identified previously suggests a role for estrogens locally produced in the regulation of sensory and integrating functions, contrary to the widespread assumption that these functions are regulated exclusively by steroids produced in the gonads.
Asunto(s)
Aromatasa/análisis , Neuronas Aferentes/química , Neuronas Aferentes/enzimología , Rombencéfalo/química , Rombencéfalo/enzimología , Animales , Coturnix/anatomía & histología , Coturnix/fisiología , Masculino , Neuronas Aferentes/citología , Rombencéfalo/citologíaRESUMEN
The enzyme aromatase catalyzes the production of estrogens in the dorsal horn of the spinal cord where most of the nociceptive primary afferent fibers terminate. Numerous estrogen receptors are present in this area and the control of spinal aromatase activity is thought to play an important role in the estrogenic control of nociception. The coexistence of aromatase and nociceptive terminals suggests a role for aromatase cells in pain-related processes, but whether terminals releasing nociceptive neuropeptides (e.g., substance P) actually contact aromatase neurons is unknown and the factors that control spinal aromatase activity have not yet been identified. In the present study we analyzed by double-label immunocytochemistry the distribution in the Japanese quail spinal cord, of aromatase and of substance P or its receptor (neurokinin 1 receptor). All antigens were mainly localized in laminae I and II as observed in mammals. Most aromatase neurons were colocalized with neurokinin 1 receptors and were in close apposition with substance P-immunoreactive fibers. These results suggest that aromatase neurons are responsive to noxious stimulation and may participate in the control of nociception. Furthermore, spinal aromatase activity could be controlled by substance P through a regulation of the aromatase gene transcription as reported for the mouse diencephalon and/or through neurokinin 1 receptor-dependent phosphorylation of the aromatase protein.
Asunto(s)
Aromatasa/metabolismo , Coturnix , Células del Asta Posterior/citología , Codorniz/fisiología , Sustancia P/metabolismo , Sinapsis/metabolismo , Andrógenos/metabolismo , Animales , Estrógenos/metabolismo , Inmunohistoquímica , Masculino , Nociceptores/metabolismo , Células del Asta Posterior/metabolismo , Codorniz/anatomía & histología , Receptores de Neuroquinina-1/metabolismo , Receptores de Neuroquinina-1/ultraestructura , Sinapsis/ultraestructuraRESUMEN
The presence of aromatase (estrogen synthase) in neurons in the dorsal horn of the spinal cord in Japanese quail suggests that estrogens produced locally from androgens could control spinal sensory processes including nociception. We used the hot water nociceptive test (54 degrees C) to appraise the long-term effect of an inhibition of aromatization on the foot withdrawal latency in male quail. Four weeks after the ablation of their main source of testosterone (testes), castrated males displayed a significantly higher foot withdrawal latency than gonadally intact males. A prolonged treatment with subcutaneous capsules filled with testosterone or 17 beta-estradiol restored the baseline latency within 2 weeks. The effect of testosterone in castrated quail was almost completely blocked by systemic injections of Vorozole(TM), a nonsteroidal aromatase inhibitor or tamoxifen, an estrogen receptor antagonist (one injection per day for 10 days). Taken together, these data demonstrate for the first time to our knowledge an effect of estrogens formed by aromatization of androgens on nociception. Because aromatase-immunoreactive neurons and aromatase activity are present in the dorsal horns of the spinal cord, this control of pain thresholds is presumably mediated, at least in part, by estrogens produced at the spinal level that act locally via slow, presumably genomic, mechanisms mediated by the activation of spinal nuclear estrogen receptors.
Asunto(s)
Aromatasa/análisis , Células del Asta Posterior/enzimología , Animales , Aromatasa/biosíntesis , Inhibidores de la Aromatasa , Coturnix , Inhibidores Enzimáticos/farmacología , Masculino , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/métodos , Células del Asta Posterior/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Médula Espinal/enzimologíaRESUMEN
In order to provide a framework for ongoing analyses of the neuronal connections of the insular cortex of the macaque monkey using modern high-resolution methods, we examined its anatomical organization in serial coronal sections stained alternately with Nissl and Gallyas (myelin) techniques. We observed the same 15 distinct architectonic areas in 10 brains. Within the granular, dysgranular, and agranular regions described in prior studies, we identified 4, 4, and 7 distinct areas, respectively. Across brains, these areas have consistent architectonic characteristics, and in flat map reconstructions they display a consistent topological or neighborhood arrangement, despite variations in the size of individual areas between cases. The borders between areas are generally rather sharply defined. Some areas, in particular the dysgranular areas, appear to consistently contain subtle transitions that suggest possible subareas or modules within the well-delimited areas. The presence of a distinct granular area that straddles the fundus of the superior limiting sulcus over its entire posterior-to-anterior extent is consistent with the available evidence on interoceptive thalamocortical projections, and also with the tensile anchor theory of species-specific cortical gyrification. These observations are consonant with the model of homeostatic afferent processing in the primate insula, and they suggest that discrete modules within insular cortex provide the basis for its polymodal integration of all salient activity relevant to ongoing emotional behavior.