RESUMO
Our previous study revealed that acupuncture may exhibit therapeutic effects on Alzheimer's disease (AD) through the activation of metabolism in memory-related brain regions. However, the underlying functional mechanism remains poorly understood and warrants further investigation. In this study, we used resting-state functional magnetic resonance imaging (rsfMRI) to explore the potential effect of electroacupuncture (EA) on the 5xFAD mouse model of AD. We found that the EA group exhibited significant improvements in the number of platforms crossed and the time spent in the target quadrant when compared with the Model group (p < 0.05). The functional connectivity (FC) of left hippocampus (Hip) was enhanced significantly among 12 regions of interest (ROIs) in the EA group (p < 0.05). Based on the left Hip as the seed point, the rsfMRI analysis of the entire brain revealed increased FC between the limbic system and the neocortex in the 5xFAD mice after EA treatment. Additionally, the expression of amyloid-ß(Aß) protein and deposition in the Hip showed a downward trend in the EA group compared to the Model group (p < 0.05). In conclusion, our findings indicate that EA treatment can improve the learning and memory abilities and inhibit the expression of Aß protein and deposition of 5xFAD mice. This improvement may be attributed to the enhancement of the resting-state functional activity and connectivity within the limbic-neocortical neural circuit, which are crucial for cognition, motor function, as well as spatial learning and memory abilities in AD mice.
Assuntos
Doença de Alzheimer , Eletroacupuntura , Neocórtex , Camundongos , Animais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/terapia , Doença de Alzheimer/metabolismo , Eletroacupuntura/métodos , Peptídeos beta-Amiloides/metabolismo , Hipocampo/metabolismo , Neocórtex/diagnóstico por imagem , Neocórtex/metabolismo , Aprendizagem Espacial , Modelos Animais de Doenças , Camundongos TransgênicosRESUMO
The hypothalamus ("hypo" meaning below, and "thalamus" meaning bed) consists of regulatory circuits that support basic life functions that ensure survival. Sitting at the interface between peripheral, environmental, and neural inputs, the hypothalamus integrates these sensory inputs to influence a range of physiologies and behaviors. Unlike the neocortex, in which a stereotyped cytoarchitecture mediates complex functions across a comparatively small number of neuronal fates, the hypothalamus comprises upwards of thousands of distinct cell types that form redundant yet functionally discrete circuits. With single-cell RNA sequencing studies revealing further cellular heterogeneity and modern photonic tools enabling high-resolution dissection of complex circuitry, a new era of hypothalamic mapping has begun. Here, we provide a general overview of mammalian hypothalamic organization, development, and connectivity to help welcome newcomers into this exciting field.
Assuntos
Hipotálamo , Neurogênese , Animais , Hipotálamo/fisiologia , Hipotálamo/ultraestrutura , Mamíferos , Neocórtex/citologia , Neocórtex/fisiologia , Neurônios/fisiologia , Tálamo/fisiologia , Análise da Expressão Gênica de Célula ÚnicaRESUMO
OBJECTIVE: To characterize ictal EEG change in the centromedian (CM) and anterior nucleus (AN) of the thalamus, using stereoelectroencephalography (SEEG) recordings. METHODS: Forty habitual seizures were analyzed in nine patients with pediatric-onset neocortical drug-resistant epilepsy who underwent SEEG (age 2-25 y) with thalamic coverage. Both visual and quantitative analysis was used to evaluate ictal EEG signal in the cortex and thalamus. The amplitude and cortico-thalamic latencies of broadband frequencies at ictal onset were measured. RESULTS: Visual analysis demonstrated consistent detection of ictal EEG changes in both the CM nucleus and AN nucleus with latency to thalamic ictal EEG changes of less than 400 ms in 95% of seizures, with low-voltage fast activity being the most common ictal pattern. Quantitative broadband amplitude analysis showed consistent power changes across the frequency bands, corresponding to ictal EEG onset, while while ictal EEG latency was variable from -18.0 seconds to 13.2 seconds. There was no significant difference between detection of CM and AN ictal activity on visual or amplitude analysis. Four patients with subsequent thalamic responsive neurostimulation (RNS) demonstrated ictal EEG changes consistent with SEEG findings. CONCLUSIONS: Ictal EEG changes were consistently seen at the CM and AN of the thalamus during neocortical seizures. SIGNIFICANCE: It may be feasible to use a closed-loop system in the thalamus to detect and modulate seizure activity for neocortical epilepsy.
Assuntos
Epilepsias Parciais , Epilepsia , Neocórtex , Criança , Humanos , Pré-Escolar , Adolescente , Adulto Jovem , Adulto , Epilepsias Parciais/diagnóstico , Epilepsia/diagnóstico , Convulsões , Tálamo , EletroencefalografiaRESUMO
Sensory inputs are conveyed to distinct primary areas of the neocortex through specific thalamocortical axons (TCA). While TCA have the ability to reorient postnatally to rescue embryonic mistargeting and target proper modality-specific areas, how this remarkable adaptive process is regulated remains largely unknown. Here, using a mutant mouse model with a shifted TCA trajectory during embryogenesis, we demonstrated that TCA rewiring occurs during a short postnatal time window, preceded by a prenatal apoptosis of thalamic neurons-two processes that together lead to the formation of properly innervated albeit reduced primary sensory areas. We furthermore showed that preterm birth, through serotonin modulation, impairs early postnatal TCA plasticity, as well as the subsequent delineation of cortical area boundary. Our study defines a birth and serotonin-sensitive period that enables concerted adaptations of TCA to primary cortical areas with major implications for our understanding of brain wiring in physiological and preterm conditions.
Assuntos
Neocórtex , Nascimento Prematuro , Recém-Nascido , Camundongos , Animais , Humanos , Gravidez , Feminino , Neurônios/fisiologia , Serotonina , Córtex Cerebral/fisiologia , Recém-Nascido Prematuro , Axônios/fisiologia , Tálamo/fisiologiaRESUMO
BACKGROUND: Alterations within large-scale brain networks-namely, the default mode (DMN) and salience networks (SN)-are present among individuals with posttraumatic stress disorder (PTSD). Previous real-time functional magnetic resonance imaging (fMRI) and electroencephalography neurofeedback studies suggest that regulating posterior cingulate cortex (PCC; the primary hub of the posterior DMN) activity may reduce PTSD symptoms and recalibrate altered network dynamics. However, PCC connectivity to the DMN and SN during PCC-targeted fMRI neurofeedback remains unexamined and may help to elucidate neurophysiological mechanisms through which these symptom improvements may occur. METHODS: Using a trauma/emotion provocation paradigm, we investigated psychophysiological interactions over a single session of neurofeedback among PTSD (n = 14) and healthy control (n = 15) participants. We compared PCC functional connectivity between regulate (in which participants downregulated PCC activity) and view (in which participants did not exert regulatory control) conditions across the whole-brain as well as in a priori specified regions-of-interest. RESULTS: During regulate as compared to view conditions, only the PTSD group showed significant PCC connectivity with anterior DMN (dmPFC, vmPFC) and SN (posterior insula) regions, whereas both groups displayed PCC connectivity with other posterior DMN areas (precuneus/cuneus). Additionally, as compared with controls, the PTSD group showed significantly greater PCC connectivity with the SN (amygdala) during regulate as compared to view conditions. Moreover, linear regression analyses revealed that during regulate as compared to view conditions, PCC connectivity to DMN and SN regions was positively correlated to psychiatric symptoms across all participants. CONCLUSION: In summary, observations of PCC connectivity to the DMN and SN provide emerging evidence of neural mechanisms underlying PCC-targeted fMRI neurofeedback among individuals with PTSD. This supports the use of PCC-targeted neurofeedback as a means by which to recalibrate PTSD-associated alterations in neural connectivity within the DMN and SN, which together, may help to facilitate improved emotion regulation abilities in PTSD.
Assuntos
Neocórtex , Neurorretroalimentação , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/terapia , Giro do Cíngulo , Neurorretroalimentação/métodos , Imageamento por Ressonância Magnética , Rede de Modo Padrão/patologia , Encéfalo , Tonsila do Cerebelo , Mapeamento EncefálicoRESUMO
The thalamus is the main gateway for sensory information from the periphery to the mammalian cerebral cortex. A major conundrum has been the discrepancy between the thalamus's central role as the primary feedforward projection system into the neocortex and the sparseness of thalamocortical synapses. Here we use new methods, combining genetic tools and scalable tissue expansion microscopy for whole-cell synaptic mapping, revealing the number, density and size of thalamic versus cortical excitatory synapses onto individual layer 2/3 (L2/3) pyramidal cells (PCs) of the mouse primary visual cortex. We find that thalamic inputs are not only sparse, but remarkably heterogeneous in number and density across individual dendrites and neurons. Most surprising, despite their sparseness, thalamic synapses onto L2/3 PCs are smaller than their cortical counterparts. Incorporating these findings into fine-scale, anatomically faithful biophysical models of L2/3 PCs reveals how individual neurons with sparse and weak thalamocortical synapses, embedded in small heterogeneous neuronal ensembles, may reliably 'read out' visually driven thalamic input.
Assuntos
Neocórtex , Tálamo , Camundongos , Animais , Tálamo/fisiologia , Neurônios/fisiologia , Sinapses/fisiologia , Células Piramidais , MamíferosRESUMO
Status epilepticus (SE) is a life-threatening emergency that can result in de novo development or worsening of epilepsy. We tested the hypothesis that the aberrant cortical output during neocortical focal status epilepticus (FSE) would induce structural and functional changes in the thalamus that might contribute to hyperexcitability in the thalamocortical circuit. We induced neocortical FSE by unilateral epidural application of convulsant drugs to the somatosensory cortex of anesthetized mice of both sexes. The resulting focal EEG ictal episodes were associated with behavioral seizures consisting of contralateral focal myoclonic activity and persisted for 2-3 h. Ten and 30 days later, brains were processed for either immunohistochemistry (IHC) or in vitro slice recordings. Sections from the center of the thalamic reticular nucleus (nRT, see methods), the ventral posterolateral nucleus (VPL), and the ventral posteromedial nucleus (VPM) from the ventrobasal nucleus (VB) were used to measure density of NeuN-immunoreactive neurons, GFAP-reactive astrocytes, and colocalized areas for VGLUT1 + PSD95- and VGLUT2 + PSD95-IR, presumptive excitatory synapses of cortical and thalamic origins. Whole-cell voltage-clamp recordings were used to measure spontaneous EPSC frequency in these nuclei. We found that the nRT showed no decrease in numbers of neurons or evidence of reactive astrogliosis. In contrast, there were increases in GFAP-IR and decreased neuronal counts of NeuN positive cells in VB. Dual IHC for VGLUT1-PSD95 and VGLUT2-PSD95 in VB showed increased numbers of excitatory synapses, likely of both thalamic and cortical origins. The frequency, but not the amplitude of sEPSCs was increased in nRT and VB neurons. SIGNIFICANCE STATEMENT: Previous reports have shown that prolonged neocortical seizures can induce injury to downstream targets that might contribute to long-term consequences of FSE. Effects of FSE in thalamic structures may disrupt normal thalamo-cortical network functions and contribute to behavioral abnormalities and post-SE epileptogenesis. Our results show that a single episode of focal neocortical SE in vivo has chronic consequences including cell loss in VB nuclei and increased excitatory connectivity in intra-thalamic and cortico-thalamic networks. Additional experiments will assess the functional consequences of these alterations and approaches to mitigate cell loss and alterations in synaptic connectivity.
Assuntos
Neocórtex , Estado Epiléptico , Masculino , Feminino , Camundongos , Animais , Tálamo , Neurônios , Núcleos Talâmicos/fisiologia , ConvulsõesRESUMO
A hallmark of non-rapid eye movement sleep is the coordinated interplay of slow oscillations (SOs) and sleep spindles. Traditionally, a cortico-thalamo-cortical loop is suggested to coordinate these rhythms: neocortically-generated SOs trigger spindles in the thalamus that are projected back to neocortex. Here, we used intrathalamic recordings from human epilepsy patients to test this canonical interplay. We show that SOs in the anterior thalamus precede neocortical SOs (peak -50 ms), whereas concurrently-recorded SOs in the mediodorsal thalamus are led by neocortical SOs (peak +50 ms). Sleep spindles, detected in both thalamic nuclei, preceded their neocortical counterparts (peak -100 ms) and were initiated during early phases of thalamic SOs. Our findings indicate an active role of the anterior thalamus in organizing sleep rhythms in the neocortex and highlight the functional diversity of thalamic nuclei in humans. The thalamic coordination of sleep oscillations could have broad implications for the mechanisms underlying memory consolidation.
Assuntos
Neocórtex , Sono de Ondas Lentas , Eletroencefalografia , Humanos , Sono , TálamoRESUMO
Investigating links between nervous system function and behavior requires monitoring neuronal activity at a range of spatial and temporal scales. Here, we summarize recent progress in applying two distinct but complementary approaches to the study of network dynamics in the neocortex. Mesoscopic calcium imaging allows simultaneous monitoring of activity across most of the cortex at moderate spatiotemporal resolution. Electrophysiological recordings provide extremely high temporal resolution of neural signals at multiple targeted locations. A number of recent studies have used these tools to reveal novel patterns of activity across distributed cortical subnetworks. This growing body of work strongly supports the hypothesis that the dynamic coordination of spatially distinct regions is a fundamental aspect of cortical function that supports cognition and behavior.
Assuntos
Neocórtex , Neocórtex/fisiologia , Neurônios/fisiologia , Cognição , Fenômenos Eletrofisiológicos , CálcioAssuntos
Epilepsia , Neocórtex , Pulvinar , Humanos , Pulvinar/fisiologia , Técnicas Estereotáxicas , TálamoRESUMO
Neuronal abundance and thickness of each cortical layer are specific to each area, but how this fundamental feature arises during development remains poorly understood. While some of area-specific features are controlled by intrinsic cues such as morphogens and transcription factors, the exact influence and mechanisms of action by cues extrinsic to the cortex, in particular the thalamic axons, have not been fully established. Here, we identify a thalamus-derived factor, VGF, which is indispensable for thalamocortical axons to maintain the proper amount of layer 4 neurons in the mouse sensory cortices. This process is prerequisite for further maturation of the primary somatosensory area, such as barrel field formation instructed by a neuronal activity-dependent mechanism. Our results provide an actual case in which highly site-specific axon projection confers further regional complexity upon the target field through locally secreting signaling molecules from axon terminals.
Assuntos
Neocórtex , Animais , Axônios/fisiologia , Camundongos , Neocórtex/fisiologia , Neurônios/fisiologia , Terminações Pré-Sinápticas , Córtex Somatossensorial/fisiologia , Tálamo/fisiologiaRESUMO
Information processing is energetically expensive. In the mammalian brain, it is unclear how information coding and energy use are regulated during food scarcity. Using whole-cell recordings and two-photon imaging in layer 2/3 mouse visual cortex, we found that food restriction reduced AMPA receptor conductance, reducing synaptic ATP use by 29%. Neuronal excitability was nonetheless preserved by a compensatory increase in input resistance and a depolarized resting potential. Consequently, neurons spiked at similar rates as controls but spent less ATP on underlying excitatory currents. This energy-saving strategy had a cost because it amplified the variability of visually-evoked subthreshold responses, leading to a 32% broadening of orientation tuning and impaired fine visual discrimination. This reduction in coding precision was associated with reduced levels of the fat mass-regulated hormone leptin and was restored by exogenous leptin supplementation. Our findings reveal that metabolic state dynamically regulates the energy spent on coding precision in neocortex.
Assuntos
Neocórtex , Córtex Visual , Animais , Mamíferos , Camundongos , Neocórtex/fisiologia , Neurônios/fisiologia , Técnicas de Patch-Clamp , Receptores de AMPA , Córtex Visual/fisiologiaRESUMO
Auditory evoked fields (AEFs) are commonly studied, yet their underlying neural mechanisms remain poorly understood. Here, we used the biophysical modelling software Human Neocortical Neurosolver (HNN) whose foundation is a canonical neocortical circuit model to interpret the cell and network mechanisms contributing to macroscale AEFs elicited by a simple tone, measured with magnetoencephalography. We found that AEFs can be reproduced by activating the neocortical circuit through a layer specific sequence of feedforward and feedback excitatory synaptic drives, similar to prior simulation of somatosensory evoked responses, supporting the notion that basic structures and activation patterns are preserved across sensory regions. We also applied the modeling framework to develop and test predictions on neural mechanisms underlying AEF differences in the left and right hemispheres, as well as in hemispheres contralateral and ipsilateral to the presentation of the auditory stimulus. We found that increasing the strength of the excitatory synaptic cortical feedback inputs to supragranular layers simulates the commonly observed right hemisphere dominance, while decreasing the input latencies and simultaneously increasing the number of cells contributing to the signal accounted for the contralateral dominance. These results provide a direct link between human data and prior animal studies and lay the foundation for future translational research examining the mechanisms underlying alteration in this fundamental biomarker of auditory processing in healthy cognition and neuropathology.
Assuntos
Neocórtex , Estimulação Acústica/métodos , Animais , Percepção Auditiva/fisiologia , Potenciais Evocados Auditivos/fisiologia , Humanos , Magnetoencefalografia/métodosRESUMO
The brain has a remarkable capacity to acquire and store memories that can later be selectively recalled. These processes are supported by the hippocampus which is thought to index memory recall by reinstating information stored across distributed neocortical circuits. However, the mechanism that supports this interaction remains unclear. Here, in humans, we show that recall of a visual cue from a paired associate is accompanied by a transient increase in the ratio between glutamate and GABA in visual cortex. Moreover, these excitatory-inhibitory fluctuations are predicted by activity in the hippocampus. These data suggest the hippocampus gates memory recall by indexing information stored across neocortical circuits using a disinhibitory mechanism.
Memories are stored by distributed groups of neurons in the brain, with individual neurons contributing to multiple memories. In a part of the brain called the neocortex, memories are held in a silent state through a balance between excitatory and inhibitory activity. This is to prevent them from being disrupted by incoming information. When a memory is recalled, an area of the brain called the hippocampus is thought to instruct the neocortex to activate the appropriate neuronal network. But how the hippocampus and neocortex coordinate their activity to switch memories 'on' and 'off' is unclear. The answer may lie in the fact that neurons in the neocortex consist of two broad types: excitatory and inhibitory. Excitatory neurons increase the activity of other neurons. They do this by releasing a chemical called glutamate. Inhibitory neurons reduce the activity of other neurons, by releasing a chemical called GABA. Koolschijn, Shpektor et al. hypothesized that the hippocampus activates memories by changing the balance of excitatory and inhibitory activity in neocortex. To test this idea, Koolschijn, Shpektor et al. invited healthy volunteers to explore a virtual reality environment. The volunteers learned that specific sounds in the environment predicted the appearance of particular visual patterns. The next day, the volunteers returned to the environment and viewed these patterns again. After each pattern, they were invited to open a virtual box. Volunteers learned that some patterns led to money in the virtual box, while other patterns did not. Finally, on day three, the volunteers listened to the sounds from day one again, this time while lying in a brain scanner. The volunteers' task was to infer whether each of the sounds would lead to money. Given that the sounds were never directly paired with the content of the virtual box, the volunteers had to solve the task by recalling the associated visual patterns. As they did so, the brain scanner measured their overall brain activity. It also assessed the relative levels of excitatory and inhibitory activity in visual areas of the neocortex, by measuring glutamate and GABA. The results revealed that as the volunteers recalled the visual cues, activity in both the hippocampus and the visual neocortex increased. Moreover, the ratio of glutamate to GABA in visual neocortex also increased which was predicted by activity in the hippocampus. This suggests that the hippocampus reactivates memories stored in neocortex by temporarily increasing excitatory activity to release memories from inhibitory control. Disturbances in the balance of excitation and inhibition occur in various neuropsychiatric disorders, including schizophrenia, autism, epilepsy and Tourette's syndrome. Damage to the hippocampus is known to cause amnesia. The current findings suggest that memories may become inaccessible or may be activated inappropriately when the interaction between the hippocampus and neocortex goes awry. Future studies could test this possibility in clinical populations.
Assuntos
Hipocampo/fisiologia , Rememoração Mental , Neocórtex/fisiologia , Inibição Neural , Plasticidade Neuronal , Estimulação Acústica , Associação , Vias Auditivas/fisiologia , Percepção Auditiva , Mapeamento Encefálico , Sinais (Psicologia) , Feminino , Ácido Glutâmico/metabolismo , Hipocampo/diagnóstico por imagem , Hipocampo/metabolismo , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Neocórtex/diagnóstico por imagem , Neocórtex/metabolismo , Estimulação Luminosa , Fatores de Tempo , Vias Visuais/fisiologia , Percepção Visual , Adulto Jovem , Ácido gama-Aminobutírico/metabolismoRESUMO
Slow-wave sleep is characterized by near-synchronous alternation of active Up states and quiescent Down states in the neocortex. Although the cortex itself can maintain these oscillations, the full expression of Up-Down states requires intact thalamocortical circuits. Sensory thalamic input can drive the cortex into an Up state. Here we show that midline thalamic neurons terminate Up states synchronously across cortical areas. Combining local field potential, single-unit, and patch-clamp recordings in conjunction with optogenetic stimulation and silencing in mice in vivo, we report that thalamic input mediates Down transition via activation of layer 1 neurogliaform inhibitory neurons acting on GABAB receptors. These results strengthen the evidence that thalamocortical interactions are essential for the full expression of slow-wave sleep, show that Down transition is an active process mediated by cortical GABAB receptors, and demonstrate that thalamus synchronizes Down transitions across cortical areas during natural slow-wave sleep.
Assuntos
Interneurônios/fisiologia , Neocórtex/fisiologia , Receptores de GABA-B/metabolismo , Sono de Ondas Lentas/fisiologia , Tálamo/fisiologia , Animais , Potenciais Evocados , Feminino , Interneurônios/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neocórtex/citologia , Neocórtex/metabolismo , Tálamo/citologia , Tálamo/metabolismoRESUMO
The mouse model of beta-amyloid (Aß) deposition, APP/PS1-21, exhibits high brain uptake of the tau-tracer (S)-[18F]THK5117, although no neurofibrillary tangles are present in this mouse model. For this reason we investigated (S)-[18F]THK5117 off-target binding to Aß plaques and MAO-B enzyme in APP/PS1-21 transgenic (TG) mouse model of Aß deposition. APP/PS1-21 TG and wild-type (WT) control mice in four different age groups (2-26 months) were imaged antemortem by positron emission tomography with (S)-[18F]THK5117, and then brain autoradiography. Additional animals were used for immunohistochemical staining and MAO-B enzyme blocking study with deprenyl pre-treatment. Regional standardized uptake value ratios for the cerebellum revealed a significant temporal increase in (S)-[18F]THK5117 uptake in aged TG, but not WT, brain. Immunohistochemical staining revealed a similar increase in Aß plaques but not endogenous hyper-phosphorylated tau or MAO-B enzyme, and ex vivo autography showed that uptake of (S)-[18F]THK5117 co-localized with the amyloid pathology. Deprenyl hydrochloride pre-treatment reduced the binding of (S)-[18F]THK5117 in the neocortex, hippocampus, and thalamus. This study's findings suggest that increased (S)-[18F]THK5117 binding in aging APP/PS1-21 TG mice is mainly due to increasing Aß deposition, and to a lesser extent binding to MAO-B enzyme, but not hyper-phosphorylated tau.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/metabolismo , Encéfalo/diagnóstico por imagem , Monoaminoxidase/metabolismo , Placa Amiloide/diagnóstico por imagem , Proteínas tau/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Compostos de Anilina , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Hipocampo/diagnóstico por imagem , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Camundongos , Camundongos Transgênicos , Inibidores da Monoaminoxidase/farmacologia , Neocórtex/diagnóstico por imagem , Neocórtex/efeitos dos fármacos , Neocórtex/metabolismo , Placa Amiloide/metabolismo , Tomografia por Emissão de Pósitrons , Presenilina-1/genética , Quinolinas , Compostos Radiofarmacêuticos , Selegilina/farmacologia , Tálamo/diagnóstico por imagem , Tálamo/efeitos dos fármacos , Tálamo/metabolismoRESUMO
Omega-3 (n-3) polyunsaturated fatty acids (PUFA) and the endocannabinoid system (ECS) modulate several functions through neurodevelopment including synaptic plasticity mechanisms. The interplay between n-3PUFA and the ECS during the early stages of development, however, is not fully understood. This study investigated the effects of maternal n-3PUFA supplementation (n-3Sup) or deficiency (n-3Def) on ECS and synaptic markers in postnatal offspring. Female rats were fed with a control, n-3Def, or n-3Sup diet from 15 days before mating and during pregnancy. The cerebral cortex and hippocampus of mothers and postnatal 1-2 days offspring were analyzed. In the mothers, a n-3 deficiency reduced CB1 receptor (CB1R) protein levels in the cortex and increased CB2 receptor (CB2R) in both cortex and hippocampus. In neonates, a maternal n-3 deficiency reduced the hippocampal CB1R amount while it increased CB2R. Additionally, total GFAP isoform expression was increased in both cortex and hippocampus in neonates of the n-3Def group. Otherwise, maternal n-3 supplementation increased the levels of n-3-derived endocannabinoids, DHEA and EPEA, in the cortex and hippocampus and reduced 2-arachidonoyl-glycerol (2-AG) concentrations in the cortex of the offspring. Furthermore, maternal n-3 supplementation also increased PKA phosphorylation in the cortex and ERK phosphorylation in the hippocampus. Synaptophysin immunocontent in both regions was also increased. In vitro assays showed that the increase of synaptophysin in the n-3Sup group was independent of CB1R activation. The findings show that variations in maternal dietary omega-3 PUFA levels may impact differently on the ECS and molecular markers in the cerebral cortex and hippocampus of the progeny.
Assuntos
Endocanabinoides/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Hipocampo/fisiologia , Neocórtex/fisiologia , Animais , Animais Recém-Nascidos , Células Cultivadas , Dieta , Feminino , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Ratos , Sinapses/metabolismoRESUMO
The isocortex of all mammals studied to date shows a progressive increase in the amount and continuity of background activity during early development. In humans the transition from a discontinuous (mostly silent, intermittently bursting) cortex to one that is continuously active is complete soon after birth and is a critical prognostic indicator. In the visual cortex of rodents this switch from discontinuous to continuous background activity occurs during the 2 d before eye-opening, driven by activity changes in relay thalamus. The factors that regulate the timing of continuity development, which enables mature visual processing, are unknown. Here, we test the role of the retina, the primary input, in the development of continuous spontaneous activity in the visual cortex of mice using depth electrode recordings from enucleated mice in vivo Bilateral enucleation at postnatal day (P)6, one week before the onset of continuous activity, acutely silences cortex, yet firing rates and early oscillations return to normal within 2 d and show a normal developmental trajectory through P12. Enucleated animals showed differences in silent period duration and continuity on P13 that resolved on P16, and an increase in low frequency power that did not. Our results show that the timing of cortical activity development is not determined by the major driving input to the system. Rather, even during a period of rapid increase in firing rates and continuity, neural activity in the visual cortex is under homeostatic control that is largely robust to the loss of the primary input.
Assuntos
Neocórtex , Córtex Visual , Animais , Homeostase , Camundongos , Tálamo , Percepção VisualRESUMO
Neurobiological models of emotion focus traditionally on limbic/paralimbic regions as neural substrates of emotion generation, and insular cortex (in conjunction with isocortical anterior cingulate cortex, ACC) as the neural substrate of feelings. An emerging view, however, highlights the importance of isocortical regions beyond insula and ACC for the subjective feeling of emotions. We used music to evoke feelings of joy and fear, and multivariate pattern analysis (MVPA) to decode representations of feeling states in functional magnetic resonance (fMRI) data of n = 24 participants. Most of the brain regions providing information about feeling representations were neocortical regions. These included, in addition to granular insula and cingulate cortex, primary and secondary somatosensory cortex, premotor cortex, frontal operculum, and auditory cortex. The multivoxel activity patterns corresponding to feeling representations emerged within a few seconds, gained in strength with increasing stimulus duration, and replicated results of a hypothesis-generating decoding analysis from an independent experiment. Our results indicate that several neocortical regions (including insula, cingulate, somatosensory and premotor cortices) are important for the generation and modulation of feeling states. We propose that secondary somatosensory cortex, which covers the parietal operculum and encroaches on the posterior insula, is of particular importance for the encoding of emotion percepts, i.e., preverbal representations of subjective feeling.
Assuntos
Emoções/fisiologia , Potenciais Evocados Auditivos , Giro do Cíngulo/fisiologia , Música , Neocórtex/fisiologia , Córtex Somatossensorial/fisiologia , Estimulação Acústica , Adulto , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
Neural cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterized by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and astrocytes. While the region-specific molecular diversity of neurons and astrocytes is increasingly understood, whether these cells share region-specific programs remains unknown. Here, we show that in the neocortex and thalamus, neurons and astrocytes express shared region-specific transcriptional and epigenetic signatures. These signatures not only distinguish cells across these two brain regions but are also detected across substructures within regions, such as distinct thalamic nuclei, where clonal analysis reveals the existence of common nucleus-specific progenitors for neurons and astrocytes. Consistent with their shared molecular signature, regional specificity is maintained following astrocyte-to-neuron reprogramming. A detailed understanding of these regional-specific signatures may thus inform strategies for future cell-based brain repair.