RESUMEN
The basic building block of the cerebral cortex, the pyramidal cell, has been shown to be characterized by a markedly different dendritic structure among layers, cortical areas, and species. Functionally, differences in the structure of their dendrites and axons are critical in determining how neurons integrate information. However, within the human cortex, these neurons have not been quantified in detail. In the present work, we performed intracellular injections of Lucifer Yellow and 3D reconstructed over 200 pyramidal neurons, including apical and basal dendritic and local axonal arbors and dendritic spines, from human occipital primary visual area and associative temporal cortex. We found that human pyramidal neurons from temporal cortex were larger, displayed more complex apical and basal structural organization, and had more spines compared to those in primary sensory cortex. Moreover, these human neocortical neurons displayed specific shared and distinct characteristics in comparison to previously published human hippocampal pyramidal neurons. Additionally, we identified distinct morphological features in human neurons that set them apart from mouse neurons. Lastly, we observed certain consistent organizational patterns shared across species. This study emphasizes the existing diversity within pyramidal cell structures across different cortical areas and species, suggesting substantial species-specific variations in their computational properties.
Asunto(s)
Células Piramidales , Humanos , Células Piramidales/fisiología , Animales , Masculino , Femenino , Ratones , Adulto , Espinas Dendríticas/fisiología , Espinas Dendríticas/ultraestructura , Lóbulo Temporal/citología , Dendritas/fisiología , Persona de Mediana Edad , Axones/fisiología , Especificidad de la EspecieRESUMEN
A central assumption of neuroscience is that long-term memories are represented by the same brain areas that encode sensory stimuli1. Neurons in inferotemporal (IT) cortex represent the sensory percept of visual objects using a distributed axis code2-4. Whether and how the same IT neural population represents the long-term memory of visual objects remains unclear. Here we examined how familiar faces are encoded in the IT anterior medial face patch (AM), perirhinal face patch (PR) and temporal pole face patch (TP). In AM and PR we observed that the encoding axis for familiar faces is rotated relative to that for unfamiliar faces at long latency; in TP this memory-related rotation was much weaker. Contrary to previous claims, the relative response magnitude to familiar versus unfamiliar faces was not a stable indicator of familiarity in any patch5-11. The mechanism underlying the memory-related axis change is likely intrinsic to IT cortex, because inactivation of PR did not affect axis change dynamics in AM. Overall, our results suggest that memories of familiar faces are represented in AM and perirhinal cortex by a distinct long-latency code, explaining how the same cell population can encode both the percept and memory of faces.
Asunto(s)
Reconocimiento Facial , Memoria a Largo Plazo , Reconocimiento en Psicología , Lóbulo Temporal , Animales , Cara , Reconocimiento Facial/fisiología , Macaca mulatta/fisiología , Memoria a Largo Plazo/fisiología , Neuronas/fisiología , Corteza Perirrinal/fisiología , Corteza Perirrinal/citología , Estimulación Luminosa , Reconocimiento en Psicología/fisiología , Lóbulo Temporal/anatomía & histología , Lóbulo Temporal/citología , Lóbulo Temporal/fisiología , RotaciónRESUMEN
Retaining information in working memory is a demanding process that relies on cognitive control to protect memoranda-specific persistent activity from interference1,2. However, how cognitive control regulates working memory storage is unclear. Here we show that interactions of frontal control and hippocampal persistent activity are coordinated by theta-gamma phase-amplitude coupling (TG-PAC). We recorded single neurons in the human medial temporal and frontal lobe while patients maintained multiple items in their working memory. In the hippocampus, TG-PAC was indicative of working memory load and quality. We identified cells that selectively spiked during nonlinear interactions of theta phase and gamma amplitude. The spike timing of these PAC neurons was coordinated with frontal theta activity when cognitive control demand was high. By introducing noise correlations with persistently active neurons in the hippocampus, PAC neurons shaped the geometry of the population code. This led to higher-fidelity representations of working memory content that were associated with improved behaviour. Our results support a multicomponent architecture of working memory1,2, with frontal control managing maintenance of working memory content in storage-related areas3-5. Within this framework, hippocampal TG-PAC integrates cognitive control and working memory storage across brain areas, thereby suggesting a potential mechanism for top-down control over sensory-driven processes.
Asunto(s)
Hipocampo , Memoria a Corto Plazo , Neuronas , Adulto , Femenino , Humanos , Masculino , Potenciales de Acción , Cognición/fisiología , Lóbulo Frontal/fisiología , Lóbulo Frontal/citología , Ritmo Gamma/fisiología , Hipocampo/fisiología , Hipocampo/citología , Memoria a Corto Plazo/fisiología , Neuronas/fisiología , Lóbulo Temporal/fisiología , Lóbulo Temporal/citología , Ritmo Teta/fisiología , Persona de Mediana EdadRESUMEN
Our understanding of the neurobiology of primate behaviour largely derives from artificial tasks in highly controlled laboratory settings, overlooking most natural behaviours that primate brains evolved to produce1-3. How primates navigate the multidimensional social relationships that structure daily life4 and shape survival and reproductive success5 remains largely unclear at the single-neuron level. Here we combine ethological analysis, computer vision and wireless recording technologies to identify neural signatures of natural behaviour in unrestrained, socially interacting pairs of rhesus macaques. Single-neuron and population activity in the prefrontal and temporal cortex robustly encoded 24 species-typical behaviours, as well as social context. Male-female partners demonstrated near-perfect reciprocity in grooming, a key behavioural mechanism supporting friendships and alliances6, and neural activity maintained a running account of these social investments. Confronted with an aggressive intruder, behavioural and neural population responses reflected empathy and were buffered by the presence of a partner. Our findings reveal a highly distributed neurophysiological ledger of social dynamics, a potential computational foundation supporting communal life in primate societies, including our own.
Asunto(s)
Encéfalo , Macaca mulatta , Neuronas , Conducta Social , Animales , Femenino , Masculino , Agresión/fisiología , Encéfalo/citología , Encéfalo/fisiología , Empatía , Aseo Animal , Procesos de Grupo , Macaca mulatta/clasificación , Macaca mulatta/fisiología , Macaca mulatta/psicología , Corteza Prefrontal/citología , Corteza Prefrontal/fisiología , Lóbulo Temporal/citología , Lóbulo Temporal/fisiología , Neuronas/fisiologíaRESUMEN
Understanding the neural basis of speech perception requires that we study the human brain both at the scale of the fundamental computational unit of neurons and in their organization across the depth of cortex. Here we used high-density Neuropixels arrays1-3 to record from 685 neurons across cortical layers at nine sites in a high-level auditory region that is critical for speech, the superior temporal gyrus4,5, while participants listened to spoken sentences. Single neurons encoded a wide range of speech sound cues, including features of consonants and vowels, relative vocal pitch, onsets, amplitude envelope and sequence statistics. Neurons at each cross-laminar recording exhibited dominant tuning to a primary speech feature while also containing a substantial proportion of neurons that encoded other features contributing to heterogeneous selectivity. Spatially, neurons at similar cortical depths tended to encode similar speech features. Activity across all cortical layers was predictive of high-frequency field potentials (electrocorticography), providing a neuronal origin for macroelectrode recordings from the cortical surface. Together, these results establish single-neuron tuning across the cortical laminae as an important dimension of speech encoding in human superior temporal gyrus.
Asunto(s)
Corteza Auditiva , Neuronas , Percepción del Habla , Lóbulo Temporal , Humanos , Estimulación Acústica , Corteza Auditiva/citología , Corteza Auditiva/fisiología , Neuronas/fisiología , Fonética , Habla , Percepción del Habla/fisiología , Lóbulo Temporal/citología , Lóbulo Temporal/fisiología , Señales (Psicología) , ElectrodosRESUMEN
The temporal lobe of the human brain contains the entorhinal cortex (EC). This region of the brain is a highly interconnected integrative hub for sensory and spatial information; it also has a key role in episodic memory formation and is the main source of cortical hippocampal inputs1-4. The human EC continues to develop during childhood5, but neurogenesis and neuronal migration to the EC are widely considered to be complete by birth. Here we show that the human temporal lobe contains many young neurons migrating into the postnatal EC and adjacent regions, with a large tangential stream persisting until the age of around one year and radial dispersal continuing until around two to three years of age. By contrast, we found no equivalent postnatal migration in rhesus macaques (Macaca mulatta). Immunostaining and single-nucleus RNA sequencing of ganglionic eminence germinal zones, the EC stream and the postnatal EC revealed that most migrating cells in the EC stream are derived from the caudal ganglionic eminence and become LAMP5+RELN+ inhibitory interneurons. These late-arriving interneurons could continue to shape the processing of sensory and spatial information well into postnatal life, when children are actively interacting with their environment. The EC is one of the first regions of the brain to be affected in Alzheimer's disease, and previous work has linked cognitive decline to the loss of LAMP5+RELN+ cells6,7. Our investigation reveals that many of these cells arrive in the EC through a major postnatal migratory stream in early childhood.
Asunto(s)
Movimiento Celular , Neuronas , Lóbulo Temporal , Animales , Preescolar , Humanos , Lactante , Corteza Entorrinal/citología , Corteza Entorrinal/fisiología , Eminencia Ganglionar/citología , Interneuronas/citología , Interneuronas/fisiología , Macaca mulatta , Neuronas/citología , Neuronas/fisiología , Análisis de Expresión Génica de una Sola Célula , Lóbulo Temporal/citología , Lóbulo Temporal/crecimiento & desarrolloRESUMEN
Single-cell transcriptomic studies have identified a conserved set of neocortical cell types from small postmortem cohorts. We extended these efforts by assessing cell type variation across 75 adult individuals undergoing epilepsy and tumor surgeries. Nearly all nuclei map to one of 125 robust cell types identified in the middle temporal gyrus. However, we found interindividual variance in abundances and gene expression signatures, particularly in deep-layer glutamatergic neurons and microglia. A minority of donor variance is explainable by age, sex, ancestry, disease state, and cell state. Genomic variation was associated with expression of 150 to 250 genes for most cell types. This characterization of cellular variation provides a baseline for cell typing in health and disease.
Asunto(s)
Lóbulo Temporal , Transcriptoma , Adulto , Humanos , Epilepsia/metabolismo , Perfilación de la Expresión Génica , Neuronas/metabolismo , Lóbulo Temporal/citología , Lóbulo Temporal/metabolismo , Enfermedades del Sistema Nervioso/genética , Trastornos Mentales/genéticaRESUMEN
We present a unique, extensive, and open synaptic physiology analysis platform and dataset. Through its application, we reveal principles that relate cell type to synaptic properties and intralaminar circuit organization in the mouse and human cortex. The dynamics of excitatory synapses align with the postsynaptic cell subclass, whereas inhibitory synapse dynamics partly align with presynaptic cell subclass but with considerable overlap. Synaptic properties are heterogeneous in most subclass-to-subclass connections. The two main axes of heterogeneity are strength and variability. Cell subclasses divide along the variability axis, whereas the strength axis accounts for substantial heterogeneity within the subclass. In the human cortex, excitatory-to-excitatory synaptic dynamics are distinct from those in the mouse cortex and vary with depth across layers 2 and 3.
Asunto(s)
Neocórtex/fisiología , Vías Nerviosas , Neuronas/fisiología , Sinapsis/fisiología , Transmisión Sináptica , Adulto , Animales , Conjuntos de Datos como Asunto , Potenciales Postsinápticos Excitadores , Femenino , Humanos , Potenciales Postsinápticos Inhibidores , Masculino , Ratones , Ratones Transgénicos , Modelos Neurológicos , Neocórtex/citología , Lóbulo Temporal/citología , Lóbulo Temporal/fisiología , Corteza Visual/citología , Corteza Visual/fisiologíaRESUMEN
Assemblies of neurons, called concepts cells, encode acquired concepts in human Medial Temporal Lobe. Those concept cells that are shared between two assemblies have been hypothesized to encode associations between concepts. Here we test this hypothesis in a computational model of attractor neural networks. We find that for concepts encoded in sparse neural assemblies there is a minimal fraction cmin of neurons shared between assemblies below which associations cannot be reliably implemented; and a maximal fraction cmax of shared neurons above which single concepts can no longer be retrieved. In the presence of a periodically modulated background signal, such as hippocampal oscillations, recall takes the form of association chains reminiscent of those postulated by theories of free recall of words. Predictions of an iterative overlap-generating model match experimental data on the number of concepts to which a neuron responds.
Asunto(s)
Memoria/fisiología , Modelos Neurológicos , Neuronas/citología , Biología Computacional , Hipocampo/citología , Hipocampo/fisiología , Humanos , Red Nerviosa/citología , Red Nerviosa/fisiología , Lóbulo Temporal/citología , Lóbulo Temporal/fisiologíaRESUMEN
Concept neurons in the medial temporal lobe respond to semantic features of presented stimuli. Analyzing 61 concept neurons recorded from twelve patients who underwent surgery to treat epilepsy, we show that firing patterns of concept neurons encode relations between concepts during a picture comparison task. Thirty-three of these responded to non-preferred stimuli with a delayed but well-defined onset whenever the task required a comparison to a response-eliciting concept, but not otherwise. Supporting recent theories of working memory, concept neurons increased firing whenever attention was directed towards this concept and could be reactivated after complete activity silence. Population cross-correlations of pairs of concept neurons exhibited order-dependent asymmetric peaks specifically when their response-eliciting concepts were to be compared. Our data are consistent with synaptic mechanisms that support reinstatement of concepts and their relations after activity silence, flexibly induced through task-specific sequential activation. This way arbitrary contents of experience could become interconnected in both working and long-term memory.
Asunto(s)
Formación de Concepto/fisiología , Neuronas/fisiología , Lóbulo Temporal/fisiología , Adulto , Anciano , Atención/fisiología , Toma de Decisiones/fisiología , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/cirugía , Femenino , Humanos , Masculino , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Sinapsis/fisiología , Lóbulo Temporal/citología , Adulto JovenRESUMEN
The ability to maintain a sequence of items in memory is a fundamental cognitive function. In the rodent hippocampus, the representation of sequentially organized spatial locations is reflected by the phase of action potentials relative to the theta oscillation (phase precession). We investigated whether the timing of neuronal activity relative to the theta brain oscillation also reflects sequence order in the medial temporal lobe of humans. We used a task in which human participants learned a fixed sequence of pictures and recorded single neuron and local field potential activity with implanted electrodes. We report that spikes for three consecutive items in the sequence (the preferred stimulus for each cell, as well as the stimuli immediately preceding and following it) were phase-locked at distinct phases of the theta oscillation. Consistent with phase precession, spikes were fired at progressively earlier phases as the sequence advanced. These findings generalize previous findings in the rodent hippocampus to the human temporal lobe and suggest that encoding stimulus information at distinct oscillatory phases may play a role in maintaining sequential order in memory.
Asunto(s)
Potenciales de Acción/fisiología , Epilepsia/fisiopatología , Aprendizaje/fisiología , Neuronas/fisiología , Ritmo Teta/fisiología , Adolescente , Adulto , Epilepsia/diagnóstico , Femenino , Hipocampo/citología , Hipocampo/fisiología , Humanos , Masculino , Modelos Neurológicos , Neuronas/citología , Estimulación Luminosa/métodos , Lóbulo Temporal/citología , Lóbulo Temporal/fisiología , Adulto JovenRESUMEN
In recent years, a large population of immature neurons has been documented in the paralaminar nucleus of the primate amygdala. A substantial fraction of these immature neurons differentiate into mature neurons during postnatal development or following selective lesion of the hippocampus. Notwithstanding a growing number of studies on the origin and fate of these immature neurons, fundamental questions about the life and death of these neurons remain. Here, we briefly summarize what is currently known about the immature neurons present in the primate ventral amygdala during development and in adulthood, as well as following selective hippocampal lesions. We provide evidence confirming that the distribution of immature neurons extends to the anterior portions of the entorhinal cortex and layer II of the perirhinal cortex. We also provide novel arguments derived from stereological estimates of the number of mature and immature neurons, which support the view that the migration of immature neurons from the lateral ventricle accompanies neuronal maturation in the primate amygdala at all ages. Finally, we propose and discuss the hypothesis that increased migration and maturation of neurons in the amygdala following hippocampal dysfunction may be linked to behavioral alterations associated with certain neurodevelopmental disorders.
Asunto(s)
Amígdala del Cerebelo/citología , Diferenciación Celular , Neuronas/citología , Neuronas/metabolismo , Factores de Edad , Amígdala del Cerebelo/metabolismo , Animales , Biomarcadores , Recuento de Células , Muerte Celular , Supervivencia Celular , Expresión Génica , Hipocampo/citología , Hipocampo/metabolismo , Inmunohistoquímica , Primates , Lóbulo Temporal/citología , Lóbulo Temporal/metabolismoRESUMEN
Spatial navigation and memory rely on neural systems that encode places, distances, and directions in relation to the external world or relative to the navigating organism. Place, grid, and head-direction cells form key units of world-referenced, allocentric cognitive maps, but the neural basis of self-centered, egocentric representations remains poorly understood. Here, we used human single-neuron recordings during virtual spatial navigation tasks to identify neurons providing a neural code for egocentric spatial maps in the human brain. Consistent with previous observations in rodents, these neurons represented egocentric bearings toward reference points positioned throughout the environment. Egocentric bearing cells were abundant in the parahippocampal cortex and supported vectorial representations of egocentric space by also encoding distances toward reference points. Beyond navigation, the observed neurons showed activity increases during spatial and episodic memory recall, suggesting that egocentric bearing cells are not only relevant for navigation but also play a role in human memory.
Asunto(s)
Memoria Episódica , Neuronas/fisiología , Memoria Espacial , Lóbulo Temporal/fisiología , Adulto , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Navegación Espacial , Lóbulo Temporal/citologíaRESUMEN
The question of how the brain recognizes the faces of familiar individuals has been important throughout the history of neuroscience. Cells linking visual processing to person memory have been proposed but not found. Here, we report the discovery of such cells through recordings from an area in the macaque temporal pole identified with functional magnetic resonance imaging. These cells responded to faces that were personally familiar. They responded nonlinearly to stepwise changes in face visibility and detail and holistically to face parts, reflecting key signatures of familiar face recognition. They discriminated between familiar identities, as fast as a general face identity area. The discovery of these cells establishes a new pathway for the fast recognition of familiar individuals.
Asunto(s)
Reconocimiento Facial , Memoria , Neuronas/fisiología , Lóbulo Temporal/fisiología , Animales , Mapeo Encefálico , Cara , Macaca mulatta , Imagen por Resonancia Magnética , Masculino , Lóbulo Temporal/citología , Percepción VisualRESUMEN
In the present study, we have used focused ion beam/scanning electron microscopy (FIB/SEM) to perform a study of the synaptic organization of layer III of Brodmann's area 21 in human tissue samples obtained from autopsies and biopsies. We analyzed the synaptic density, 3D spatial distribution, and type (asymmetric/symmetric), as well as the size and shape of each synaptic junction of 4945 synapses that were fully reconstructed in 3D. Significant differences in the mean synaptic density between autopsy and biopsy samples were found (0.49 and 0.66 synapses/µm3, respectively). However, in both types of samples (autopsy and biopsy), the asymmetric:symmetric ratio was similar (93:7) and most asymmetric synapses were established on dendritic spines (75%), while most symmetric synapses were established on dendritic shafts (85%). We also compared several electron microscopy methods and analysis tools to estimate the synaptic density in the same brain tissue. We have shown that FIB/SEM is much more reliable and robust than the majority of the other commonly used EM techniques. The present work constitutes a detailed description of the synaptic organization of cortical layer III. Further studies on the rest of the cortical layers are necessary to better understand the functional organization of this temporal cortical region.
Asunto(s)
Neocórtex/citología , Sinapsis/ultraestructura , Lóbulo Temporal/citología , Adulto , Autopsia , Biopsia , Recuento de Células , Espinas Dendríticas/fisiología , Espinas Dendríticas/ultraestructura , Femenino , Humanos , Imagenología Tridimensional , Masculino , Microscopía Electrónica de Rastreo , Persona de Mediana Edad , Neocórtex/ultraestructura , Neuroimagen , Lóbulo Temporal/ultraestructura , Adulto JovenRESUMEN
Pyramidal neurons are the most abundant and characteristic neuronal type in the cerebral cortex and their dendritic spines are the main postsynaptic elements of cortical excitatory synapses. Previous studies have shown that pyramidal cell structure differs across layers, cortical areas, and species. However, within the human cortex, the pyramidal dendritic morphology has been quantified in detail in relatively few cortical areas. In the present work, we performed intracellular injections of Lucifer Yellow at several distances from the temporal pole. We found regional differences in pyramidal cell morphology, which showed large inter-individual variability in most of the morphological variables measured. However, some values remained similar in all cases. The smallest and least complex cells in the most posterior temporal region showed the greatest dendritic spine density. Neurons in the temporal pole showed the greatest sizes with the highest number of spines. Layer V cells were larger, more complex, and had a greater number of dendritic spines than those in layer III. The present results suggest that, while some aspects of pyramidal structure are conserved, there are specific variations across cortical regions, and species.
Asunto(s)
Células Piramidales/ultraestructura , Lóbulo Temporal/ultraestructura , Adulto , Dendritas , Espinas Dendríticas/ultraestructura , Epilepsia/patología , Epilepsia/cirugía , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Individualidad , Masculino , Persona de Mediana Edad , Neuroimagen , Neuronas/ultraestructura , Lóbulo Temporal/citologíaRESUMEN
One of the most characteristic properties of many vertebrate neural systems is the layered organization of different cell types. This cytoarchitecture exists in the cortex, the retina, the hippocampus, and many other parts of the central nervous system. The developmental mechanisms of neural layer formation have been subject to substantial experimental efforts. Here, we provide a general computational model for cortical layer formation in 3D physical space. We show that this multiscale, agent-based model, comprising two distinct stages of apoptosis, can account for the wide range of neuronal numbers encountered in different cortical areas and species. Our results demonstrate the phenotypic richness of a basic state diagram structure. Importantly, apoptosis allows for changing the thickness of one layer without automatically affecting other layers. Therefore, apoptosis increases the flexibility for evolutionary change in layer architecture. Notably, slightly changed gene regulatory dynamics recapitulate the characteristic properties observed in neurodevelopmental diseases. Overall, we propose a novel computational model using gene-type rules, exhibiting many characteristics of normal and pathological cortical development.
Asunto(s)
Simulación por Computador , Corteza Somatosensorial/fisiología , Lóbulo Temporal/fisiología , Corteza Visual/fisiología , Animales , Corteza Cerebral/citología , Corteza Cerebral/fisiología , Humanos , Macaca , Ratones , Ratas , Corteza Somatosensorial/citología , Especificidad de la Especie , Lóbulo Temporal/citología , Corteza Visual/citologíaRESUMEN
Neurons in some sensory areas reflect the content of working memory (WM) in their spiking activity. However, this spiking activity is seldom related to behavioral performance. We studied the responses of inferotemporal (IT) neurons, which exhibit object-selective activity, along with Frontal Eye Field (FEF) neurons, which exhibit spatially selective activity, during the delay period of an object WM task. Unlike the spiking activity and local field potentials (LFPs) within these areas, which were poor predictors of behavioral performance, the phase-locking of IT spikes and LFPs with the beta band of FEF LFPs robustly predicted successful WM maintenance. In addition, IT neurons exhibited greater object-selective persistent activity when their spikes were locked to the phase of FEF LFPs. These results reveal that the coordination between prefrontal and temporal cortex predicts the successful maintenance of visual information during WM.
Asunto(s)
Macaca mulatta/fisiología , Memoria a Corto Plazo/fisiología , Neuronas/fisiología , Corteza Prefrontal/fisiología , Lóbulo Temporal/fisiología , Potenciales de Acción/fisiología , Algoritmos , Animales , Lóbulo Frontal/citología , Lóbulo Frontal/fisiología , Masculino , Modelos Neurológicos , Estimulación Luminosa , Corteza Prefrontal/citología , Lóbulo Temporal/citologíaRESUMEN
Research in functional neuroimaging has suggested that category-selective regions of visual cortex, including the ventral temporal cortex (VTC), can be reactivated endogenously through imagery and recall. Face representation in the monkey face-patch system has been well studied and is an attractive domain in which to explore these processes in humans. The VTCs of 8 human subjects (4 female) undergoing invasive monitoring for epilepsy surgery were implanted with microelectrodes. Most (26 of 33) category-selective units showed specificity for face stimuli. Different face exemplars evoked consistent and discriminable responses in the population of units sampled. During free recall, face-selective units preferentially reactivated in the absence of visual stimulation during a 2 s window preceding face recall events. Furthermore, we show that in at least 1 subject, the identity of the recalled face could be predicted by comparing activity preceding recall events to activity evoked by visual stimulation. We show that face-selective units in the human VTC are reactivated endogenously, and present initial evidence that consistent representations of individual face exemplars are specifically reactivated in this manner.SIGNIFICANCE STATEMENT The role of "top-down" endogenous reactivation of native representations in higher sensory areas is poorly understood in humans. We conducted the first detailed single-unit survey of ventral temporal cortex (VTC) in human subjects, showing that, similarly to nonhuman primates, humans encode different faces using different rate codes. Then, we demonstrated that, when subjects recalled and imagined a given face, VTC neurons reactivated with the same rate codes as when subjects initially viewed that face. This suggests that the VTC units not only carry durable representations of faces, but that those representations can be endogenously reactivated via "top-down" mechanisms.
Asunto(s)
Reconocimiento Facial , Lóbulo Temporal/fisiología , Adulto , Potenciales Evocados Visuales , Femenino , Humanos , Masculino , Recuerdo Mental , Persona de Mediana Edad , Neuronas/fisiología , Lóbulo Temporal/citologíaRESUMEN
Type 2 diabetes mellitus (T2D), characterised by peripheral insulin resistance, is a risk factor for dementia. In addition to its contribution to small and large vessel disease, T2D may directly damage cells of the brain neurovascular unit. In this study, we investigated the transcriptomic changes in cortical neurones, and associated astrocytes and endothelial cells of the neurovascular unit, in the ageing brain. Neurone, astrocyte, and endothelial cell-enriched mRNA, obtained by immuno-laser capture microdissection of temporal cortex (Brodmann area 21/22) from 6 cases with self-reported T2D in the Cognitive Function and Ageing Study neuropathology cohort, and an equal number of age and sex-matched controls, was assessed by microarray analysis. Integrated Molecular Pathway Level Analysis was performed using the Kyoto Encyclopaedia of Genes and Genomes database on significantly differentially expressed genes, defined as P < 0.05 and fold-change ± 1.2. Hub genes identified from Weighted Gene Co-expression Network Analysis were validated in neurones using the NanoString nCounter platform. The expression and cellular localisation of proteins encoded by selected candidate genes were confirmed by immunohistochemistry. 912, 2202, and 1227 genes were significantly differentially expressed between cases with self-reported T2D and controls in neurones, astrocytes, and endothelial cells respectively. Changes in cortical neurones included alterations in insulin and other signalling pathways, cell cycle, cellular senescence, inflammatory mediators, and components of the mitochondrial respiratory electron transport chain. Impaired insulin signalling was shared by neurovascular unit cells with, additionally, apoptotic pathway changes in astrocytes and dysregulation of advanced glycation end-product signalling in endothelial cells. Transcriptomic analysis identified changes in key cellular pathways associated with T2D that may contribute to neuronal damage and dysfunction. These effects on brain cells potentially contribute to a diabetic dementia, and may provide novel approaches for therapeutic intervention.