The contributions of entorhinal cortex and hippocampus to error driven learning.
Ontology highlight
ABSTRACT:
SUBMITTER: Ku SP
PROVIDER: S-EPMC8144598 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Knowing where we are, where we have been, and where we are going is critical to many behaviors, including navigation and memory. One potential neuronal mechanism underlying this ability is phase precession, in which spatially tuned neurons represent sequences of positions by activating at progressively earlier phases of local network theta oscillations. Based on studies in rodents, researchers have hypothesized that phase precession may be a general neural pattern for representing sequential events for learning and memory. By recording human single-neuron activity during spatial navigation, we show that spatially tuned neurons in the human hippocampus and entorhinal cortex exhibit phase precession. Furthermore, beyond the neural representation of locations, we show evidence for phase precession related to specific goal states. Our findings thus extend theta phase precession to humans and suggest that this phenomenon has a broad functional role for the neural representation of both spatial and non-spatial information.
| S-EPMC8195854 | biostudies-literature
Project description:Biologically realistic computer simulations of neuronal circuits require systematic data-driven modeling of neuron type-specific synaptic activity. However, limited experimental yield, heterogeneous recordings conditions, and ambiguous neuronal identification have so far prevented the consistent characterization of synaptic signals for all connections of any neural system. We introduce a strategy to overcome these challenges and report a comprehensive synaptic quantification among all known neuron types of the hippocampal-entorhinal network. First, we reconstructed >2600 synaptic traces from ∼1200 publications into a unified computational representation of synaptic dynamics. We then trained a deep learning architecture with the resulting parameters, each annotated with detailed metadata such as recording method, solutions, and temperature. The model learned to predict the synaptic properties of all 3,120 circuit connections in arbitrary conditions with accuracy approaching the intrinsic experimental variability. Analysis of data normalized and completed with the deep learning model revealed that synaptic signals are controlled by few latent variables associated with specific molecular markers and interrelating conductance, decay time constant, and short-term plasticity. We freely release the tools and full dataset of unitary synaptic values in 32 covariate settings. Normalized synaptic data can be used in brain simulations, and to predict and test experimental hypothesis.
| S-EPMC9072429 | biostudies-literature
Project description:Physical activity enhances hippocampal function but its effects on neuronal structure remain relatively unexplored outside of the dentate gyrus. Using Golgi impregnation and the lipophilic tracer DiI, we show that long-term voluntary running increases the density of dendritic spines in the entorhinal cortex and hippocampus of adult rats. Exercise was associated with increased dendritic spine density not only in granule neurons of the dentate gyrus, but also in CA1 pyramidal neurons, and in layer III pyramidal neurons of the entorhinal cortex. In the CA1 region, changes in dendritic spine density are accompanied by changes in dendritic arborization and alterations in the morphology of individual spines. These findings suggest that physical activity exerts pervasive effects on neuronal morphology in the hippocampus and one of its afferent populations. These structural changes may contribute to running-induced changes in cognitive function.
| S-EPMC2956984 | biostudies-literature
Project description:Humans learn about the world in a variety of manners, including by observation, by associating cues in the environment, and via feedback. Across species, two brain structures have been predominantly involved in these learning processes: the hippocampus--supporting learning via observation and paired association--and the striatum--critical for feedback learning. This simple dichotomy, however, has recently been challenged by reports of hippocampal engagement in feedback learning, although the role of the hippocampus is not fully understood. The purpose of this experiment was to characterize the hippocampal response during feedback learning by manipulating varying levels of memory interference. Consistent with prior reports, feedback learning recruited the striatum and midbrain. Notably, feedback learning also engaged the hippocampus. The level of activity in these regions was modulated by the degree of memory interference, such that the greatest activation occurred during the highest level of memory interference. Importantly, the accuracy of information learned via feedback correlated with hippocampal activation and was reduced by the presence of high memory interference. Taken together, these findings provide evidence of hippocampal involvement in feedback learning by demonstrating both its relevance for the accuracy of information learned via feedback and its susceptibility to interference.
| S-EPMC4641758 | biostudies-literature
Project description:The hippocampal CA1 field processes spatial information, but the relative importance of intra- vs. extra-hippocampal sources of input into CA1 for spatial behavior is unclear. To characterize the relative roles of these two sources of input, originating in the hippocampal field CA3 and in the medial entorhinal cortex (MEC), we studied effects of discrete neurotoxic lesions of CA3 or MEC on concurrent spatial and nonspatial navigation tasks, and on synaptic transmission in afferents to CA1. Lesions in CA3 or MEC regions that abolished CA3-CA1, or reduced MEC-CA1 synaptic transmission, respectively, impaired spatial navigation and unexpectedly interfered with cue response, suggesting that in certain conditions of training regimen, hippocampal activity may influence behavior otherwise supported by nonhippocampal neural networks. MEC lesions had milder and temporary behavioral effects, but also markedly amplified transmission in the CA3-CA1 pathway. Extensive behavioral training had a similar, but more modest effect on CA3-CA1 transmission. Thus, cortical input to the hippocampus modulates CA1 activity both directly and indirectly, through heterosynaptic interaction, to control information flow in the hippocampal loop. Following damage to hippocampal cortical input, the functional coupling of separate intra- and extra-hippocampal inputs to CA1 involved in normal learning may initiate processes that support recovery of behavioral function. Such a process may explain how CA3 lesions, which do not significantly modify the basic features of CA1 neural activity, nonetheless impair spatial recall, whereas lesions of EC input to CA1, which reduce the spatial selectivity of CA1 firing in foraging rats, have only mild effects on spatial navigation.
| S-EPMC4148030 | biostudies-literature
Project description:The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients of both sexes who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects' abilities to remember items located far away from boundaries. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred.SIGNIFICANCE STATEMENT Numerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory.
| S-EPMC5943975 | biostudies-literature
Project description:Despite the importance of the discharge frequency in neuronal communication, little is known about the firing-rate patterns of cortical populations. Using large-scale recordings from multiple layers of the entorhinal-hippocampal loop, we found that the firing rates of principal neurons showed a lognormal-like distribution in all brain states. Mean and peak rates within place fields of hippocampal neurons were also strongly skewed. Importantly, firing rates of the same neurons showed reliable correlations in different brain states and testing situations, as well as across familiar and novel environments. The fraction of neurons that participated in population oscillations displayed a lognormal pattern. Such skewed firing rates of individual neurons may be due to a skewed distribution of synaptic weights, which is supported by our observation of a lognormal distribution of the efficacy of spike transfer from principal neurons to interneurons. The persistent skewed distribution of firing rates implies that a preconfigured, highly active minority dominates information transmission in cortical networks.
| S-EPMC3804159 | biostudies-literature
Project description:The organization of temporal information is critical for the encoding and retrieval of episodic memories. In the rodent hippocampus and entorhinal cortex, evidence accumulated over the last decade suggests that populations of "time cells" in the hippocampus encode temporal information. We identify time cells in humans using intracranial microelectrode recordings obtained from 27 human epilepsy patients who performed an episodic memory task. We show that time cell activity predicts the temporal organization of retrieved memory items. We also uncover evidence of ramping cell activity in humans, which represents a complementary type of temporal information. These findings establish a cellular mechanism for the representation of temporal information in the human brain needed to form episodic memories.
| S-EPMC7668099 | biostudies-literature
Project description:Alzheimer's Disease (AD) is the leading form of dementia worldwide. Currently, the pathological mechanisms underlying AD are not well understood. Although the glutamatergic system is extensively implicated in its pathophysiology, there is a gap in knowledge regarding the expression of glutamate receptors in the AD brain. This study aimed to characterize the expression of specific glutamate receptor subunits in post-mortem human brain tissue using immunohistochemistry and confocal microscopy. Free-floating immunohistochemistry and confocal laser scanning microscopy were used to quantify the density of glutamate receptor subunits GluA2, GluN1, and GluN2A in specific cell layers of the hippocampal sub-regions, subiculum, entorhinal cortex, and superior temporal gyrus. Quantification of GluA2 expression in human post-mortem hippocampus revealed a significant increase in the stratum (str.) moleculare of the dentate gyrus (DG) in AD compared with control. Increased GluN1 receptor expression was found in the str. moleculare and hilus of the DG, str. oriens of the CA2 and CA3, str. pyramidale of the CA2, and str. radiatum of the CA1, CA2, and CA3 subregions and the entorhinal cortex. GluN2A expression was significantly increased in AD compared with control in the str. oriens, str. pyramidale, and str. radiatum of the CA1 subregion. These findings indicate that the expression of glutamatergic receptor subunits shows brain region-specific changes in AD, suggesting possible pathological receptor functioning. These results provide evidence of specific glutamatergic receptor subunit changes in the AD hippocampus and entorhinal cortex, indicating the requirement for further research to elucidate the pathophysiological mechanisms it entails, and further highlight the potential of glutamatergic receptor subunits as therapeutic targets.
| S-EPMC8549033 | biostudies-literature
Project description:The hippocampal formation displays a wide range of physiological responses to different spatial manipulations of the environment. However, very few attempts have been made to identify core computational principles underlying those hippocampal responses. Here, we capitalize on the observation that the entorhinal-hippocampal complex (EHC) forms a closed loop and projects inhibitory signals "countercurrent" to the trisynaptic pathway to build a self-supervised model that learns to reconstruct its own inputs by error backpropagation. The EHC is then abstracted as an autoencoder, with the hidden layers acting as an information bottleneck. With the inputs mimicking the firing activity of lateral and medial entorhinal cells, our model is shown to generate place cells and to respond to environmental manipulations as observed in rodent experiments. Altogether, we propose that the hippocampus builds conjunctive compressed representations of the environment by learning to reconstruct its own entorhinal inputs via gradient descent.
| S-EPMC8091892 | biostudies-literature