Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Quantitative properties of a feedback circuit predict frequency-dependent pattern separation.

ABSTRACT: Feedback inhibitory motifs are thought to be important for pattern separation across species. How feedback circuits may implement pattern separation of biologically plausible, temporally structured input in mammals is, however, poorly understood. We have quantitatively determined key properties of netfeedback inhibition in the mouse dentate gyrus, a region critically involved in pattern separation. Feedback inhibition is recruited steeply with a low dynamic range (0% to 4% of active GCs), and with a non-uniform spatial profile. Additionally, net feedback inhibition shows frequency-dependent facilitation, driven by strongly facilitating mossy fiber inputs. Computational analyses show a significant contribution of the feedback circuit to pattern separation of theta modulated inputs, even within individual theta cycles. Moreover, pattern separation was selectively boosted at gamma frequencies, in particular for highly similar inputs. This effect was highly robust, suggesting that frequency-dependent pattern separation is a key feature of the feedback inhibitory microcircuit.

SUBMITTER: Braganza O

PROVIDER: S-EPMC7032930 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Accurate prediction of gene feedback circuit behavior from component properties.

Project description:A basic assumption underlying synthetic biology is that analysis of genetic circuit elements, such as regulatory proteins and promoters, can be used to understand and predict the behavior of circuits containing those elements. To test this assumption, we used time-lapse fluorescence microscopy to quantitatively analyze two autoregulatory negative feedback circuits. By measuring the gene regulation functions of the corresponding repressor-promoter interactions, we accurately predicted the expression level of the autoregulatory feedback loops, in molecular units. This demonstration that quantitative characterization of regulatory elements can predict the behavior of genetic circuits supports a fundamental requirement of synthetic biology.

| S-EPMC2132446 | biostudies-literature

Early Deficits in Dentate Circuit and Behavioral Pattern Separation after Concussive Brain Injury.

Project description:Traumatic brain injury leads to cellular and circuit changes in the dentate gyrus, a gateway to hippocampal information processing. Intrinsic granule cell firing properties and strong feedback inhibition in the dentate are proposed as critical to its ability to generate unique representation of similar inputs by a process known as pattern separation. Here we evaluate the impact of brain injury on cellular decorrelation of temporally patterned inputs in slices and behavioral discrimination of spatial locations in vivo one week after concussive lateral fluid percussion injury (FPI) in mice. Despite posttraumatic increases in perforant path evoked excitatory drive to granule cells and enhanced ΔFosB labeling, indicating sustained increase in excitability, the reliability of granule cell spiking was not compromised after FPI. Although granule cells continued to effectively decorrelate output spike trains recorded in response to similar temporally patterned input sets after FPI, their ability to decorrelate highly similar input patterns was reduced. In parallel, encoding of similar spatial locations in a novel object location task that involves the dentate inhibitory circuits was impaired one week after FPI. Injury induced changes in pattern separation were accompanied by loss of somatostatin expressing inhibitory neurons in the hilus. Together, these data suggest that the early posttraumatic changes in the dentate circuit undermine dentate circuit decorrelation of temporal input patterns as well as behavioral discrimination of similar spatial locations, both of which could contribute to deficits in episodic memory.

| S-EPMC10515770 | biostudies-literature

Topology-dependent interference of synthetic gene circuit function by growth feedback.

Project description:Growth-mediated feedback between synthetic gene circuits and host organisms leads to diverse emerged behaviors, including growth bistability and enhanced ultrasensitivity. However, the range of possible impacts of growth feedback on gene circuits remains underexplored. Here we mathematically and experimentally demonstrated that growth feedback affects the functions of memory circuits in a network topology-dependent way. Specifically, the memory of the self-activation switch is quickly lost due to the growth-mediated dilution of the circuit products. Decoupling of growth feedback reveals its memory, manifested by its hysteresis property across a broad range of inducer concentration. On the contrary, the toggle switch is more refractory to growth-mediated dilution and can retrieve its memory after the fast-growth phase. The underlying principle lies in the different dependence of active and repressive regulations in these circuits on the growth-mediated dilution. Our results unveil the topology-dependent mechanism on how growth-mediated feedback influences the behaviors of gene circuits.

| S-EPMC7246135 | biostudies-literature

GATA Factor-Dependent Positive-Feedback Circuit in Acute Myeloid Leukemia Cells.

Project description:The master regulatory transcription factor GATA-2 triggers hematopoietic stem and progenitor cell generation. GATA2 haploinsufficiency is implicated in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), and GATA2 overexpression portends a poor prognosis for AML. However, the constituents of the GATA-2-dependent genetic network mediating pathogenesis are unknown. We described a p38-dependent mechanism that phosphorylates GATA-2 and increases GATA-2 target gene activation. We demonstrate that this mechanism establishes a growth-promoting chemokine/cytokine circuit in AML cells. p38/ERK-dependent GATA-2 phosphorylation facilitated positive autoregulation of GATA2 transcription and expression of target genes, including IL1B and CXCL2. IL-1? and CXCL2 enhanced GATA-2 phosphorylation, which increased GATA-2-mediated transcriptional activation. p38/ERK-GATA-2 stimulated AML cell proliferation via CXCL2 induction. As GATA2 mRNA correlated with IL1B and CXCL2 mRNAs in AML-M5 and high expression of these genes predicted poor prognosis of cytogenetically normal AML, we propose that the circuit is functionally important in specific AML contexts.

| S-EPMC5154384 | biostudies-literature

Multiplexing of Theta and Alpha Rhythms in the Amygdala-Hippocampal Circuit Supports Pattern Separation of Emotional Information.

Project description:How do we remember emotional events? While emotion often leads to vivid recollection, the precision of emotional memories can be degraded, especially when discriminating among overlapping experiences in memory (i.e., pattern separation). Communication between the amygdala and the hippocampus has been proposed to support emotional memory, but the exact neural mechanisms remain unclear. Here, we used intracranial recordings in pre-surgical epilepsy patients to show that successful pattern separation of emotional stimuli is associated with theta band (3-7 Hz)-coordinated bidirectional interactions between the amygdala and the hippocampus. In contrast, discrimination errors (i.e., failure to discriminate similar stimuli) were associated with alpha band (7-13 Hz)-coordinated unidirectional influence from the amygdala to the hippocampus. These findings imply that alpha band synchrony may impair discrimination of similar emotional events via the amygdala-hippocampal directional coupling, which suggests a target for treatments of psychiatric conditions such as post-traumatic stress disorder, in which aversive experiences are often overgeneralized.

| S-EPMC6605056 | biostudies-literature

Project description:While aging is generally associated with episodic memory decline, not all older adults exhibit memory loss. Furthermore, emotional memories are not subject to the same extent of forgetting and appear preserved in aging. We conducted high-resolution fMRI during a task involving pattern separation of emotional information in older adults with and without age-related memory impairment (characterized by performance on a word-list learning task: low performers: LP vs. high performers: HP). We found signals consistent with emotional pattern separation in hippocampal dentate (DG)/CA3 in HP but not in LP individuals, suggesting a deficit in emotional pattern separation. During false recognition, we found increased DG/CA3 activity in LP individuals, suggesting that hyperactivity may be associated with overgeneralization. We additionally observed a selective deficit in basolateral amygdala-lateral entorhinal cortex-DG/CA3 functional connectivity in LP individuals during pattern separation of negative information. During negative false recognition, LP individuals showed increased medial temporal lobe functional connectivity, consistent with overgeneralization. Overall, these results suggest a novel mechanistic account of individual differences in emotional memory alterations exhibited in aging.

| S-EPMC5909956 | biostudies-literature

A circuit-dependent ROS feedback loop mediates glutamate excitotoxicity to sculpt the Drosophila motor system.

Project description:Overproduction of reactive oxygen species (ROS) is known to mediate glutamate excitotoxicity in neurological diseases. However, how ROS burdens can influence neural circuit integrity remains unclear. Here, we investigate the impact of excitotoxicity induced by depletion of Drosophila Eaat1, an astrocytic glutamate transporter, on locomotor central pattern generator (CPG) activity, neuromuscular junction architecture, and motor function. We show that glutamate excitotoxicity triggers a circuit-dependent ROS feedback loop to sculpt the motor system. Excitotoxicity initially elevates ROS, thereby inactivating cholinergic interneurons and consequently changing CPG output activity to overexcite motor neurons and muscles. Remarkably, tonic motor neuron stimulation boosts muscular ROS, gradually dampening muscle contractility to feedback-enhance ROS accumulation in the CPG circuit and subsequently exacerbate circuit dysfunction. Ultimately, excess premotor excitation of motor neurons promotes ROS-activated stress signaling that alters neuromuscular junction architecture. Collectively, our results reveal that excitotoxicity-induced ROS can perturb motor system integrity through a circuit-dependent mechanism.

| S-EPMC6682402 | biostudies-literature

Pattern-dependent, simultaneous plasticity differentially transforms the input-output relationship of a feedforward circuit.

Project description:Memories are believed to be encoded by changes in the synaptic connections between neurons. Although many forms of synaptic plasticity have been identified, it remains unknown how such changes affect local circuits. Feedforward inhibitory networks are a common type of local circuitry and occur when principal neurons and their afferent inhibitory interneurons receive the same input. Using slices of cerebellar cortex, we explored how synaptic plasticity at multiple sites within a feedforward inhibitory network consisting of parallel fibers, interneurons, and Purkinje neurons alters the output of this circuit. We found that stimuli resembling baseline activity potentiated feedforward excitatory and simultaneously depressed feedforward inhibitory pathways. In contrast, stimuli resembling sensory-evoked patterns of firing potentiated both types of feedforward connections. These distinct forms of ensemble plasticity change the way Purkinje neurons subsequently respond to inputs. Such concerted changes in the circuitry of cerebellar cortex may contribute to certain forms of sensorimotor learning.

| S-EPMC1253560 | biostudies-literature

Pattern separation and pattern completion: Behaviorally separable processes?

Project description:Episodic memory capacity requires several processes, including mnemonic discrimination of similar experiences, termed pattern separation, and holistic retrieval of multidimensional experiences given a cue, termed pattern completion. Both computations seem to rely on the hippocampus proper, but they also seem to be instantiated by distinct hippocampal subfields. Thus, we investigated whether individual differences in behavioral expressions of pattern separation and pattern completion were correlated after accounting for general mnemonic ability. Young adult participants learned events comprised of a scene-animal-object triad. In the pattern separation task, we estimated mnemonic discrimination using lure classification for events that contained a similar lure element. In the pattern completion task, we estimated holistic recollection using dependency in retrieval success for different associations from the same event. Although overall accuracies for the two tasks correlated as expected, specific measures of individual variation in holistic retrieval and mnemonic discrimination did not correlate, suggesting that these two processes involve distinguishable properties of episodic memory.

| S-EPMC7819938 | biostudies-literature

Hunger states switch a flip-flop memory circuit via a synaptic AMPK-dependent positive feedback loop.

Project description:Synaptic plasticity in response to changes in physiologic state is coordinated by hormonal signals across multiple neuronal cell types. Here, we combine cell-type-specific electrophysiological, pharmacological, and optogenetic techniques to dissect neural circuits and molecular pathways controlling synaptic plasticity onto AGRP neurons, a population that regulates feeding. We find that food deprivation elevates excitatory synaptic input, which is mediated by a presynaptic positive feedback loop involving AMP-activated protein kinase. Potentiation of glutamate release was triggered by the orexigenic hormone ghrelin and exhibited hysteresis, persisting for hours after ghrelin removal. Persistent activity was reversed by the anorexigenic hormone leptin, and optogenetic photostimulation demonstrated involvement of opioid release from POMC neurons. Based on these experiments, we propose a memory storage device for physiological state constructed from bistable synapses that are flipped between two sustained activity states by transient exposure to hormones signaling energy levels.

| S-EPMC3209501 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data