RESUMEN
The entorhinal cortex represents allocentric spatial geometry and egocentric speed and heading information required for spatial navigation. However, it remains unclear whether it contributes to the prediction of an animal's future location. We discovered grid cells in the medial entorhinal cortex (MEC) that have grid fields representing future locations during goal-directed behavior. These predictive grid cells represented prospective spatial information by shifting their grid fields against the direction of travel. Predictive grid cells discharged at the trough phases of the hippocampal CA1 theta oscillation and, together with other types of grid cells, organized sequences of the trajectory from the current to future positions across each theta cycle. Our results suggest that the MEC provides a predictive map that supports forward planning in spatial navigation.
Asunto(s)
Región CA1 Hipocampal , Corteza Entorrinal , Células de Red , Navegación Espacial , Ritmo Teta , Corteza Entorrinal/fisiología , Corteza Entorrinal/citología , Animales , Navegación Espacial/fisiología , Células de Red/fisiología , Ratas , Región CA1 Hipocampal/fisiología , Región CA1 Hipocampal/citología , Masculino , Ratas Long-EvansRESUMEN
Computational simulations with data-driven physiological detail can foster a deeper understanding of the neural mechanisms involved in cognition. Here, we utilize the wealth of cellular properties from Hippocampome.org to study neural mechanisms of spatial coding with a spiking continuous attractor network model of medial entorhinal cortex circuit activity. The primary goal is to investigate if adding such realistic constraints could produce firing patterns similar to those measured in real neurons. Biological characteristics included in the work are excitability, connectivity, and synaptic signaling of neuron types defined primarily by their axonal and dendritic morphologies. We investigate the spiking dynamics in specific neuron types and the synaptic activities between groups of neurons. Modeling the rodent hippocampal formation keeps the simulations to a computationally reasonable scale while also anchoring the parameters and results to experimental measurements. Our model generates grid cell activity that well matches the spacing, size, and firing rates of grid fields recorded in live behaving animals from both published datasets and new experiments performed for this study. Our simulations also recreate different scales of those properties, e.g., small and large, as found along the dorsoventral axis of the medial entorhinal cortex. Computational exploration of neuronal and synaptic model parameters reveals that a broad range of neural properties produce grid fields in the simulation. These results demonstrate that the continuous attractor network model of grid cells is compatible with a spiking neural network implementation sourcing data-driven biophysical and anatomical parameters from Hippocampome.org. The software (version 1.0) is released as open source to enable broad community reuse and encourage novel applications.
Asunto(s)
Potenciales de Acción , Corteza Entorrinal , Células de Red , Modelos Neurológicos , Sinapsis , Animales , Células de Red/fisiología , Sinapsis/fisiología , Corteza Entorrinal/fisiología , Corteza Entorrinal/citología , Potenciales de Acción/fisiología , Simulación por Computador , Neuronas/fisiología , Neuronas/citología , Hipocampo/fisiología , Hipocampo/citología , Red Nerviosa/fisiología , Red Nerviosa/citología , Redes Neurales de la ComputaciónRESUMEN
A cognitive map is a suitably structured representation that enables novel computations using previous experience; for example, planning a new route in a familiar space1. Work in mammals has found direct evidence for such representations in the presence of exogenous sensory inputs in both spatial2,3 and non-spatial domains4-10. Here we tested a foundational postulate of the original cognitive map theory1,11: that cognitive maps support endogenous computations without external input. We recorded from the entorhinal cortex of monkeys in a mental navigation task that required the monkeys to use a joystick to produce one-dimensional vectors between pairs of visual landmarks without seeing the intermediate landmarks. The ability of the monkeys to perform the task and generalize to new pairs indicated that they relied on a structured representation of the landmarks. Task-modulated neurons exhibited periodicity and ramping that matched the temporal structure of the landmarks and showed signatures of continuous attractor networks12,13. A continuous attractor network model of path integration14 augmented with a Hebbian-like learning mechanism provided an explanation of how the system could endogenously recall landmarks. The model also made an unexpected prediction that endogenous landmarks transiently slow path integration, reset the dynamics and thereby reduce variability. This prediction was borne out in a reanalysis of firing rate variability and behaviour. Our findings link the structured patterns of activity in the entorhinal cortex to the endogenous recruitment of a cognitive map during mental navigation.
Asunto(s)
Cognición , Corteza Entorrinal , Macaca mulatta , Modelos Neurológicos , Navegación Espacial , Animales , Masculino , Cognición/fisiología , Corteza Entorrinal/fisiología , Corteza Entorrinal/citología , Macaca mulatta/fisiología , Neuronas/fisiología , Navegación Espacial/fisiología , Aprendizaje/fisiologíaRESUMEN
The hippocampus receives sequences of sensory inputs from the cortex during exploration and encodes the sequences with millisecond precision. We developed a predictive autoencoder model of the hippocampus including the trisynaptic and monosynaptic circuits from the entorhinal cortex (EC). CA3 was trained as a self-supervised recurrent neural network to predict its next input. We confirmed that CA3 is predicting ahead by analyzing the spike coupling between simultaneously recorded neurons in the dentate gyrus, CA3, and CA1 of the mouse hippocampus. In the model, CA1 neurons signal prediction errors by comparing CA3 predictions to the next direct EC input. The model exhibits the rapid appearance and slow fading of CA1 place cells and displays replay and phase precession from CA3. The model could be learned in a biologically plausible way with error-encoding neurons. Similarities between the hippocampal and thalamocortical circuits suggest that such computation motif could also underlie self-supervised sequence learning in the cortex.
Asunto(s)
Hipocampo , Aprendizaje , Animales , Ratones , Hipocampo/fisiología , Hipocampo/citología , Aprendizaje/fisiología , Modelos Neurológicos , Corteza Entorrinal/fisiología , Corteza Entorrinal/citología , Neuronas/fisiología , Región CA1 Hipocampal/fisiología , Región CA1 Hipocampal/citología , Región CA3 Hipocampal/fisiología , Región CA3 Hipocampal/citología , Ratones Endogámicos C57BL , Redes Neurales de la Computación , Masculino , Potenciales de Acción/fisiología , Giro Dentado/fisiología , Giro Dentado/citologíaRESUMEN
Synaptic excitation and inhibition are essential for neuronal communication. However, the variables that regulate synaptic excitation and inhibition in the intact brain remain largely unknown. Here, we examined how spike transmission and suppression between principal cells (PCs) and interneurons (INTs) are modulated by activity history, brain state, cell type, and somatic distance between presynaptic and postsynaptic neurons by applying cross-correlogram analyses to datasets recorded from the dorsal hippocampus and medial entorhinal cortex (MEC) of 11 male behaving and sleeping Long Evans rats. The strength, temporal delay, and brain-state dependency of the spike transmission and suppression depended on the subregions/layers. The spike transmission probability of PC-INT excitatory pairs that showed short-term depression versus short-term facilitation was higher in CA1 and lower in CA3. Likewise, the intersomatic distance affected the proportion of PC-INT excitatory pairs that showed short-term depression and facilitation in the opposite manner in CA1 compared with CA3. The time constant of depression was longer, while that of facilitation was shorter in MEC than in CA1 and CA3. During sharp-wave ripples, spike transmission showed a larger gain in the MEC than in CA1 and CA3. The intersomatic distance affected the spike transmission gain during sharp-wave ripples differently in CA1 versus CA3. A subgroup of MEC layer 3 (EC3) INTs preferentially received excitatory inputs from and inhibited MEC layer 2 (EC2) PCs. The EC2 PC-EC3 INT excitatory pairs, most of which showed short-term depression, exhibited higher spike transmission probabilities than the EC2 PC-EC2 INT and EC3 PC-EC3 INT excitatory pairs. EC2 putative stellate cells exhibited stronger spike transmission to and received weaker spike suppression from EC3 INTs than EC2 putative pyramidal cells. This study provides detailed comparisons of monosynaptic interaction dynamics in the hippocampal-entorhinal loop, which may help to elucidate circuit operations.
Asunto(s)
Potenciales de Acción , Corteza Entorrinal , Hipocampo , Interneuronas , Ratas Long-Evans , Transmisión Sináptica , Animales , Masculino , Corteza Entorrinal/fisiología , Corteza Entorrinal/citología , Interneuronas/fisiología , Transmisión Sináptica/fisiología , Hipocampo/fisiología , Potenciales de Acción/fisiología , Ratas , Inhibición Neural/fisiología , Células Piramidales/fisiologíaRESUMEN
The medial entorhinal cortex (MEC) hosts many of the brain's circuit elements for spatial navigation and episodic memory, operations that require neural activity to be organized across long durations of experience1. Whereas location is known to be encoded by spatially tuned cell types in this brain region2,3, little is known about how the activity of entorhinal cells is tied together over time at behaviourally relevant time scales, in the second-to-minute regime. Here we show that MEC neuronal activity has the capacity to be organized into ultraslow oscillations, with periods ranging from tens of seconds to minutes. During these oscillations, the activity is further organized into periodic sequences. Oscillatory sequences manifested while mice ran at free pace on a rotating wheel in darkness, with no change in location or running direction and no scheduled rewards. The sequences involved nearly the entire cell population, and transcended epochs of immobility. Similar sequences were not observed in neighbouring parasubiculum or in visual cortex. Ultraslow oscillatory sequences in MEC may have the potential to couple neurons and circuits across extended time scales and serve as a template for new sequence formation during navigation and episodic memory formation.
Asunto(s)
Corteza Entorrinal , Neuronas , Periodicidad , Animales , Ratones , Corteza Entorrinal/citología , Corteza Entorrinal/fisiología , Neuronas/fisiología , Giro Parahipocampal/fisiología , Carrera/fisiología , Factores de Tiempo , Oscuridad , Corteza Visual/fisiología , Vías Nerviosas , Navegación Espacial/fisiología , Memoria EpisódicaRESUMEN
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
Memory formation involves binding of contextual features into a unitary representation1-4, whereas memory recall can occur using partial combinations of these contextual features. The neural basis underlying the relationship between a contextual memory and its constituent features is not well understood; in particular, where features are represented in the brain and how they drive recall. Here, to gain insight into this question, we developed a behavioural task in which mice use features to recall an associated contextual memory. We performed longitudinal imaging in hippocampus as mice performed this task and identified robust representations of global context but not of individual features. To identify putative brain regions that provide feature inputs to hippocampus, we inhibited cortical afferents while imaging hippocampus during behaviour. We found that whereas inhibition of entorhinal cortex led to broad silencing of hippocampus, inhibition of prefrontal anterior cingulate led to a highly specific silencing of context neurons and deficits in feature-based recall. We next developed a preparation for simultaneous imaging of anterior cingulate and hippocampus during behaviour, which revealed robust population-level representation of features in anterior cingulate, that lag hippocampus context representations during training but dynamically reorganize to lead and target recruitment of context ensembles in hippocampus during recall. Together, we provide the first mechanistic insights into where contextual features are represented in the brain, how they emerge, and how they access long-range episodic representations to drive memory recall.
Asunto(s)
Giro del Cíngulo , Hipocampo , Recuerdo Mental , Modelos Neurológicos , Animales , Mapeo Encefálico , Corteza Entorrinal/citología , Corteza Entorrinal/fisiología , Giro del Cíngulo/citología , Giro del Cíngulo/fisiología , Hipocampo/citología , Hipocampo/fisiología , Estudios Longitudinales , Recuerdo Mental/fisiología , Ratones , Inhibición NeuralRESUMEN
The medial entorhinal cortex is part of a neural system for mapping the position of an individual within a physical environment1. Grid cells, a key component of this system, fire in a characteristic hexagonal pattern of locations2, and are organized in modules3 that collectively form a population code for the animal's allocentric position1. The invariance of the correlation structure of this population code across environments4,5 and behavioural states6,7, independent of specific sensory inputs, has pointed to intrinsic, recurrently connected continuous attractor networks (CANs) as a possible substrate of the grid pattern1,8-11. However, whether grid cell networks show continuous attractor dynamics, and how they interface with inputs from the environment, has remained unclear owing to the small samples of cells obtained so far. Here, using simultaneous recordings from many hundreds of grid cells and subsequent topological data analysis, we show that the joint activity of grid cells from an individual module resides on a toroidal manifold, as expected in a two-dimensional CAN. Positions on the torus correspond to positions of the moving animal in the environment. Individual cells are preferentially active at singular positions on the torus. Their positions are maintained between environments and from wakefulness to sleep, as predicted by CAN models for grid cells but not by alternative feedforward models12. This demonstration of network dynamics on a toroidal manifold provides a population-level visualization of CAN dynamics in grid cells.
Asunto(s)
Células de Red/fisiología , Modelos Neurológicos , Potenciales de Acción , Animales , Corteza Entorrinal/anatomía & histología , Corteza Entorrinal/citología , Corteza Entorrinal/fisiología , Células de Red/clasificación , Masculino , Ratas , Ratas Long-Evans , Sueño/fisiología , Percepción Espacial/fisiología , Vigilia/fisiologíaRESUMEN
The estrous cycle is caused by the changing concentration of ovarian hormones, particularly 17ß-estradiol, a hormone whose effect on excitatory circuits has been extensively reported. However, fewer studies have tried to elucidate how this cycle, or this hormone, affects the plasticity of inhibitory networks and the structure of interneurons. Among these cells, somatostatin-expressing O-LM neurons of the hippocampus are especially interesting. They have a role in the modulation of theta oscillations, and they receive direct input from the entorhinal cortex, which place them in the center of hippocampal function. In this study, we report that the expression of polysialylated form of the neural cell adhesion molecule (PSA-NCAM) in the hippocampus, a molecule involved in the plasticity of somatostatin-expressing interneurons in the adult brain, fluctuated through the different stages of the estrous cycle. Likewise, these stages and the expression of PSA-NCAM affected the density of dendritic spines of O-LM cells. We also describe that 17ß-estradiol replacement of adult ovariectomized female mice caused an increase in the perisomatic inhibitory puncta in O-LM interneurons as well as an increase in their axonal bouton density. Interestingly, this treatment also induced a decrease in their dendritic spine density, specifically in O-LM interneurons lacking PSA-NCAM expression. Finally, using an ex vivo real-time assay with entorhinal-hippocampal organotypic cultures, we show that this hormone decreased the dynamics in spinogenesis, altogether highlighting the modulatory effect that 17ß-estradiol has on inhibitory circuits.
Asunto(s)
Corteza Entorrinal/fisiología , Estradiol/metabolismo , Hipocampo/fisiología , Interneuronas/fisiología , Red Nerviosa/fisiología , Molécula L1 de Adhesión de Célula Nerviosa/metabolismo , Ácidos Siálicos/metabolismo , Animales , Células Cultivadas , Espinas Dendríticas/fisiología , Corteza Entorrinal/citología , Corteza Entorrinal/metabolismo , Femenino , Hipocampo/citología , Hipocampo/metabolismo , Interneuronas/metabolismo , Ratones , Ratones Transgénicos , Red Nerviosa/metabolismo , Ovariectomía , Somatostatina/metabolismoRESUMEN
Specific classes of GABAergic neurons play specific roles in regulating information processing in the brain. In the hippocampus, two major classes, parvalbumin-expressing (PV+) and somatostatin-expressing (SST+), differentially regulate endogenous firing patterns and target subcellular compartments of principal cells. How these classes regulate the flow of information throughout the hippocampus is poorly understood. We hypothesize that PV+ and SST+ interneurons in the dentate gyrus (DG) and CA3 differentially modulate CA3 patterns of output, thereby altering the influence of CA3 on CA1. We find that while suppressing either interneuron class increases DG and CA3 output, the effects on CA1 were very different. Suppressing PV+ interneurons increases local field potential signatures of coupling from CA3 to CA1 and decreases signatures of coupling from entorhinal cortex to CA1; suppressing SST+ interneurons has the opposite effect. Thus, DG and CA3 PV+ and SST+ interneurons bidirectionally modulate the flow of information through the hippocampal circuit.
Asunto(s)
Región CA1 Hipocampal/fisiología , Región CA3 Hipocampal/fisiología , Giro Dentado/fisiología , Corteza Entorrinal/fisiología , Neuronas GABAérgicas/fisiología , Interneuronas/fisiología , Somatostatina/metabolismo , Potenciales de Acción , Animales , Región CA1 Hipocampal/citología , Región CA3 Hipocampal/citología , Giro Dentado/citología , Corteza Entorrinal/citología , Femenino , Neuronas GABAérgicas/citología , Interneuronas/citología , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Could learning that uses cognitive control to judiciously use relevant information while ignoring distractions generally improve brain function, beyond forming explicit memories? According to a neuroplasticity hypothesis for how some cognitive behavioural therapies are effective, cognitive control training (CCT) changes neural circuit information processing1-3. Here we investigated whether CCT persistently alters hippocampal neural circuit function. We show that mice learned and remembered a conditioned place avoidance during CCT that required ignoring irrelevant locations of shock. CCT facilitated learning new tasks in novel environments for several weeks, relative to unconditioned controls and control mice that avoided the same place during reduced distraction. CCT rapidly changes entorhinal cortex-to-dentate gyrus synaptic circuit function, resulting in an excitatory-inhibitory subcircuit change that persists for months. CCT increases inhibition that attenuates the dentate response to medial entorhinal cortical input, and through disinhibition, potentiates the response to strong inputs, pointing to overall signal-to-noise enhancement. These neurobiological findings support the neuroplasticity hypothesis that, as well as storing item-event associations, CCT persistently optimizes neural circuit information processing.
Asunto(s)
Cognición/fisiología , Hipocampo/fisiología , Modelos Neurológicos , Vías Nerviosas/fisiología , Plasticidad Neuronal/fisiología , Animales , Reacción de Prevención/fisiología , Región CA1 Hipocampal/citología , Región CA1 Hipocampal/fisiología , Terapia Cognitivo-Conductual , Condicionamiento Operante/fisiología , Giro Dentado/citología , Giro Dentado/fisiología , Corteza Entorrinal/citología , Corteza Entorrinal/fisiología , Femenino , Neuronas GABAérgicas , Hipocampo/citología , Potenciación a Largo Plazo , Masculino , Memoria/fisiología , Ratones , Ratones Endogámicos C57BL , Inhibición Neural , Procesamiento Espacial , Sinapsis/fisiologíaAsunto(s)
Hipocampo/citología , Hipocampo/fisiología , Neurociencias/historia , Células de Lugar/fisiología , Memoria Espacial/fisiología , Navegación Espacial/fisiología , Potenciales de Acción , Animales , Corteza Entorrinal/citología , Corteza Entorrinal/fisiología , Historia del Siglo XX , Humanos , Ratones , Microelectrodos , RatasRESUMEN
The medial entorhinal cortex (MEC)-hippocampal network plays a key role in the processing, storage, and recall of spatial information. However, how the spatial code provided by MEC inputs relates to spatial representations generated by principal cell assemblies within hippocampal subfields remains enigmatic. To investigate this coding relationship, we employed two-photon calcium imaging in mice navigating through dissimilar virtual environments. Imaging large MEC bouton populations revealed spatially tuned activity patterns. MEC inputs drastically changed their preferred spatial field locations between environments, whereas hippocampal cells showed lower levels of place field reconfiguration. Decoding analysis indicated that higher place field reliability and larger context-dependent activity-rate differences allow low numbers of principal cells, particularly in the DG and CA1, to provide information about location and context more accurately and rapidly than MEC inputs. Thus, conversion of dynamic MEC inputs into stable spatial hippocampal maps may enable fast encoding and efficient recall of spatio-contextual information.
Asunto(s)
Corteza Entorrinal/fisiología , Hipocampo/fisiología , Animales , Región CA1 Hipocampal/citología , Región CA1 Hipocampal/fisiología , Señalización del Calcio , Giro Dentado/citología , Giro Dentado/fisiología , Corteza Entorrinal/citología , Hipocampo/citología , Masculino , Recuerdo Mental/fisiología , Ratones , Ratones Endogámicos C57BL , Red Nerviosa/citología , Red Nerviosa/fisiología , Terminales Presinápticos/fisiología , Reproducibilidad de los Resultados , Percepción Espacial/fisiología , Realidad VirtualRESUMEN
Acetylcholine release in the hippocampus plays a central role in the formation of new memory representations. An influential but largely untested theory proposes that memory formation requires acetylcholine to enhance responses in CA1 to new sensory information from entorhinal cortex whilst depressing inputs from previously encoded representations in CA3. Here, we show that excitatory inputs from entorhinal cortex and CA3 are depressed equally by synaptic release of acetylcholine in CA1. However, feedforward inhibition from entorhinal cortex exhibits greater depression than CA3 resulting in a selective enhancement of excitatory-inhibitory balance and CA1 activation by entorhinal inputs. Entorhinal and CA3 pathways engage different feedforward interneuron subpopulations and cholinergic modulation of presynaptic function is mediated differentially by muscarinic M3 and M4 receptors, respectively. Thus, our data support a role and mechanisms for acetylcholine to prioritise novel information inputs to CA1 during memory formation.
Asunto(s)
Acetilcolina/metabolismo , Región CA1 Hipocampal/fisiología , Corteza Entorrinal/fisiología , Potenciales Postsinápticos Excitadores/fisiología , Retroalimentación Fisiológica/fisiología , Transmisión Sináptica/fisiología , Animales , Región CA1 Hipocampal/citología , Carbacol/farmacología , Agonistas Colinérgicos/farmacología , Corteza Entorrinal/citología , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Retroalimentación Fisiológica/efectos de los fármacos , Interneuronas/metabolismo , Interneuronas/fisiología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Técnicas de Placa-Clamp , Células Piramidales/metabolismo , Células Piramidales/fisiología , Receptor Muscarínico M3/genética , Receptor Muscarínico M3/metabolismo , Transmisión Sináptica/efectos de los fármacosRESUMEN
Mounting evidence shows that dopamine in the striatum is critically involved in reward-based reinforcement learning1,2. However, it remains unclear how dopamine reward signals influence the entorhinal-hippocampal circuit, another brain network that is crucial for learning and memory3-5. Here, using cell-type-specific electrophysiological recording6, we show that dopamine signals from the ventral tegmental area and substantia nigra control the encoding of cue-reward association rules in layer 2a fan cells of the lateral entorhinal cortex (LEC). When mice learned novel olfactory cue-reward associations using a pre-learned association rule, spike representations of LEC fan cells grouped newly learned rewarded cues with a pre-learned rewarded cue, but separated them from a pre-learned unrewarded cue. Optogenetic inhibition of fan cells impaired the learning of new associations while sparing the retrieval of pre-learned memory. Using fibre photometry, we found that dopamine sends novelty-induced reward expectation signals to the LEC. Inhibition of LEC dopamine signals disrupted the associative encoding of fan cells and impaired learning performance. These results suggest that LEC fan cells represent a cognitive map of abstract task rules, and that LEC dopamine facilitates the incorporation of new memories into this map.
Asunto(s)
Dopamina/metabolismo , Corteza Entorrinal/citología , Corteza Entorrinal/fisiología , Memoria/fisiología , Animales , Anticipación Psicológica , Señales (Psicología) , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Células Piramidales/metabolismo , RecompensaRESUMEN
Entorhinal cortical grid cells fire in a periodic pattern that tiles space, which is suggestive of a spatial coordinate system. However, irregularities in the grid pattern as well as responses of grid cells in contexts other than spatial navigation have presented a challenge to existing models of entorhinal function. In this Perspective, we propose that hippocampal input provides a key informative drive to the grid network in both spatial and non-spatial circumstances, particularly around salient events. We build on previous models in which neural activity propagates through the entorhinal-hippocampal network in time. This temporal contiguity in network activity points to temporal order as a necessary characteristic of representations generated by the hippocampal formation. We advocate that interactions in the entorhinal-hippocampal loop build a topological representation that is rooted in the temporal order of experience. In this way, the structure of grid cell firing supports a learned topology rather than a rigid coordinate frame that is bound to measurements of the physical world.
Asunto(s)
Corteza Entorrinal/fisiología , Células de Red/fisiología , Hipocampo/fisiología , Aprendizaje/fisiología , Red Nerviosa/fisiología , Percepción Espacial/fisiología , Animales , Corteza Entorrinal/citología , Hipocampo/citología , Humanos , Modelos Neurológicos , Red Nerviosa/citologíaRESUMEN
As animals navigate on a two-dimensional surface, neurons in the medial entorhinal cortex (MEC) known as grid cells are activated when the animal passes through multiple locations (firing fields) arranged in a hexagonal lattice that tiles the locomotion surface1. However, although our world is three-dimensional, it is unclear how the MEC represents 3D space2. Here we recorded from MEC cells in freely flying bats and identified several classes of spatial neurons, including 3D border cells, 3D head-direction cells, and neurons with multiple 3D firing fields. Many of these multifield neurons were 3D grid cells, whose neighbouring fields were separated by a characteristic distance-forming a local order-but lacked any global lattice arrangement of the fields. Thus, whereas 2D grid cells form a global lattice-characterized by both local and global order-3D grid cells exhibited only local order, creating a locally ordered metric for space. We modelled grid cells as emerging from pairwise interactions between fields, which yielded a hexagonal lattice in 2D and local order in 3D, thereby describing both 2D and 3D grid cells using one unifying model. Together, these data and model illuminate the fundamental differences and similarities between neural codes for 3D and 2D space in the mammalian brain.
Asunto(s)
Quirópteros/fisiología , Percepción de Profundidad/fisiología , Corteza Entorrinal/citología , Corteza Entorrinal/fisiología , Células de Red/fisiología , Modelos Neurológicos , Animales , Conducta Animal/fisiología , Vuelo Animal/fisiología , MasculinoRESUMEN
We investigated how entorhinal grid cells encode volumetric space. On a horizontal surface, grid cells usually produce multiple, spatially focal, approximately circular firing fields that are evenly sized and spaced to form a regular, close-packed, hexagonal array. This spatial regularity has been suggested to underlie navigational computations. In three dimensions, theoretically the equivalent firing pattern would be a regular, hexagonal close packing of evenly sized spherical fields. In the present study, we report that, in rats foraging in a cubic lattice, grid cells maintained normal temporal firing characteristics and produced spatially stable firing fields. However, although most grid fields were ellipsoid, they were sparser, larger, more variably sized and irregularly arranged, even when only fields abutting the lower surface (equivalent to the floor) were considered. Thus, grid self-organization is shaped by the environment's structure and/or movement affordances, and grids may not need to be regular to support spatial computations.
Asunto(s)
Potenciales de Acción/fisiología , Corteza Entorrinal/fisiología , Conducta Exploratoria/fisiología , Células de Red/fisiología , Modelos Neurológicos , Percepción Espacial/fisiología , Animales , Corteza Entorrinal/citología , Masculino , RatasRESUMEN
The hippocampus and entorhinal cortex (EC) accumulate amyloid beta peptides (Aß) that promote neuropathology in Alzheimer's disease, but the early effects of Aß on excitatory synaptic transmission in the EC have not been well characterized. To assess the acute effects of Aß1-42 on glutamatergic synapses, acute brain slices from wildtype rats were exposed to Aß1-42 or control solution for 3 hours, and tissue was analyzed using protein immunoblotting and quantitative PCR. Presynaptically, Aß1-42 induced marked reductions in synaptophysin, synapsin-2a mRNA, and mGluR3 mRNA, and increased both VGluT2 protein and Ca2+-activated channel KCa2.2 mRNA levels. Postsynaptically, Aß1-42 reduced PSD95 and GluN2B protein, and also downregulated GluN2B and GluN2A mRNA, without affecting scaffolding elements SAP97 and PICK1. mGluR5 mRNA was strongly increased, while mGluR1 mRNA was unaffected. Blocking either GluN2A- or GluN2B-containing NMDA receptors did not significantly prevent synaptic changes induced by Aß1-42, but combined blockade did prevent synaptic alterations. These findings demonstrate that Aß1-42 rapidly disrupts glutamatergic transmission in the EC through mechanisms involving concurrent activation of GluN2A- and GluN2B-containing NMDA receptors.