Gamma rhythm communication between entorhinal cortex and dentate gyrus neuronal assemblies.
Ontology highlight
ABSTRACT:
SUBMITTER: Fernandez-Ruiz A
PROVIDER: S-EPMC8285088 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Major depressive disorder (MDD) is considered a 'circuitopathy', and brain stimulation therapies hold promise for ameliorating MDD symptoms, including hippocampal dysfunction. It is unknown whether stimulation of upstream hippocampal circuitry, such as the entorhinal cortex (Ent), is antidepressive, although Ent stimulation improves learning and memory in mice and humans. Here we show that molecular targeting (Ent-specific knockdown of a psychosocial stress-induced protein) and chemogenetic stimulation of Ent neurons induce antidepressive-like effects in mice. Mechanistically, we show that Ent-stimulation-induced antidepressive-like behavior relies on the generation of new hippocampal neurons. Thus, controlled stimulation of Ent hippocampal afferents is antidepressive via increased hippocampal neurogenesis. These findings emphasize the power and potential of Ent glutamatergic afferent stimulation-previously well-known for its ability to influence learning and memory-for MDD treatment.
| S-EPMC5948139 | biostudies-literature
Project description:Local circuits in the medial entorhinal cortex (mEC) and hippocampus generate gamma frequency population rhythms independently. Temporal interaction between these areas at gamma frequencies is implicated in memory-a phenomenon linked to activity of NMDA-subtype glutamate receptors. While blockade of NMDA receptors does not affect frequency of gamma rhythms in hippocampus, it exposes a second, lower frequency (25-35 Hz) gamma rhythm in mEC. In experiment and model, NMDA receptor-dependent mEC gamma rhythms were mediated by basket interneurons, but NMDA receptor-independent gamma rhythms were mediated by a novel interneuron subtype-the goblet cell. This cell was distinct from basket cells in morphology, intrinsic membrane properties and synaptic inputs. The two different gamma frequencies matched the different intrinsic frequencies in hippocampal areas CA3 and CA1, suggesting that NMDA receptor activation may control the nature of temporal interactions between mEC and hippocampus, thus influencing the pathway for information transfer between the two regions.
| S-EPMC2587538 | biostudies-literature
Project description:Entorhinal cortical (EC)-hippocampal (HPC) circuits are crucial for learning and memory. Although it was traditionally believed that superficial layers (II/III) of the EC mainly project to the HPC and deep layers (V/VI) receive input from the HPC, recent studies have highlighted the significant projections from layers Va and VI of the EC into the HPC. However, it still remains unknown whether Vb neurons in the EC provide projections to the hippocampus. In this study, using a molecular marker for Vb and retrograde tracers, we identified that the outer layer of Vb neurons in the medial EC (MEC) directly project to both dorsal and ventral hippocampal dentate gyrus (DG), with a significant preference for the ventral DG. In contrast to the distribution of DG-projecting Vb cells, anterior thalamus-projecting Vb cells are distributed through the outer to the inner layer of Vb. Furthermore, dual tracer injections revealed that DG-projecting Vb cells and anterior thalamus-projecting Vb cells are distinct populations. These results suggest that the roles of MEC Vb neurons are not merely limited to the formation of EC-HPC loop circuits, but rather contribute to multiple neural processes for learning and memory.
| S-EPMC10845563 | biostudies-literature
Project description:Reexposure to the context associated with heroin intake provokes relapse to drug taking after abstinence. The dorsal dentate gyrus (dDG) and entorhinal cortex (EC) have been implicated in contextual memory processing, but the underlying circuit mechanisms in context-induced relapse remain poorly understood. In this study, using a self-administration rat model, we found that activation and synaptic transmission of glutamatergic projections from the EC to the upper blade of dentate gyrus (dDGub) were significantly enhanced during context-induced reinstatement of heroin seeking. This effect was associated with increased of phosphorylation of GluN2B-containing NMDA receptors (GluN2B) at Y1472, ratio of GluN2B membrane/total protein levels, and expression of downstream extracellular signal-regulated kinase-1/2 (ERK1/2) in the dDG region. Furthermore, DREADD-mediated specific inactivation of the EC-dDG pathway or disconnection of the pathway with local postsynaptic GluN2B-ERK1/2 signaling both decreased context-induced reinstatement of heroin seeking. These experimental manipulations had no effect on saccharin-reinforced responding and general locomotor activity in rats. Our results indicate that the EC-dDG pathway mediates context-induced reinstatement of heroin seeking, via the activation of postsynaptic GluN2B-ERK1/2 signaling in the dDG.
| S-EPMC5520779 | biostudies-literature
Project description:Alterations in the function of prefrontal cortex (PFC) and hippocampus have been implicated in underlying the relapse to alcohol seeking behaviors in humans and animal models of moderate to severe alcohol use disorders (AUD). Here we used chronic intermittent ethanol vapor exposure (CIE), 21d protracted abstinence following CIE (21d AB), and re-exposure to one vapor session during protracted abstinence (re-exposure) to evaluate the effects of chronic ethanol exposure on basal synaptic function, neuronal excitability and expression of key synaptic proteins that play a role in neuronal excitability in the medial PFC (mPFC) and dentate gyrus (DG). CIE consistently enhanced excitability of layer 2/3 pyramidal neurons in the mPFC and granule cell neurons in the DG. In the DG, this effect persisted during 21d AB. Re-exposure did not enhance excitability, suggesting resistance to vapor-induced effects. Analysis of action potential kinetics revealed that altered afterhyperpolarization, rise time and decay time constants are associated with the altered excitability during CIE, 21d AB and re-exposure. Molecular adaptations that may underlie increases in neuronal excitability under these different conditions were identified. Quantitative polymerase chain reaction of large-conductance potassium (BK) channel subunit mRNA in PFC and DG tissue homogenates did not show altered expression patterns of BK subunits. Western blotting demonstrates enhanced phosphorylation of Ca2⁺/calmodulin-dependent protein kinase II (CaMKII), and reduced phosphorylation of glutamate receptor GluN2A/2B subunits. These results suggest a novel relationship between activity of CaMKII and GluN receptors in the mPFC and DG, and neuronal excitability in these brain regions in the context of moderate to severe AUD.
| S-EPMC7927349 | biostudies-literature
Project description:Young adult-born granule cells (abGCs) in the dentate gyrus (DG) have a profound impact on cognition and mood. However, it remains unclear how abGCs distinctively contribute to local DG information processing. We found that the actions of abGCs in the DG depend on the origin of incoming afferents. In response to lateral entorhinal cortex (LEC) inputs, abGCs exert monosynaptic inhibition of mature granule cells (mGCs) through group II metabotropic glutamate receptors. By contrast, in response to medial entorhinal cortex (MEC) inputs, abGCs directly excite mGCs through N-methyl-d-aspartate receptors. Thus, a critical function of abGCs may be to regulate the relative synaptic strengths of LEC-driven contextual information versus MEC-driven spatial information to shape distinct neural representations in the DG.
| S-EPMC6800071 | biostudies-literature
Project description:Following prolonged perforant pathway stimulation (PPS) in rats, a seizure-free "latent period" is observed that lasts around 3 weeks. During this time, aberrant neuronal activity occurs, which has been hypothesized to contribute to the generation of an "epileptic" network. This study was designed to 1) examine the pathological network activity that occurs in the dentate gyrus during the latent period, and 2) determine whether suppressing this activity by removing the main input to the dentate gyrus could stop or prolong epileptogenesis. Immediately following PPS, continuous video-EEG monitoring was used to record spontaneous neuronal activity and detect seizures. During the latent period, low frequency oscillations (LFOs), occurring at a rate of approximately 1 Hz, were detected in the dentate gyrus of all rats that developed epilepsy. LFO incidence was apparently random, but often decreased in the hour preceding a spontaneous seizure. Bilateral transection of the perforant pathway did not impact the incidence of hippocampal LFOs, the latency to epilepsy, or hippocampal neuropathology. Our main findings are: 1) LFOs are a reliable biomarker of hippocampal epileptogenesis, and 2) removing entorhinal cortex input to the hippocampus neither reduces the occurrence of LFOs nor has a demonstrable antiepileptogenic effect.
| S-EPMC4861965 | biostudies-other
Project description:Feed-forward inhibition from molecular layer interneurons onto granule cells (GCs) in the dentate gyrus is thought to have major effects regulating entorhinal-hippocampal interactions, but the precise identity, properties, and functional connectivity of the GABAergic cells in the molecular layer are not well understood. We used single and paired intracellular patch clamp recordings from post-hoc-identified cells in acute rat hippocampal slices and identified a subpopulation of molecular layer interneurons that expressed immunocytochemical markers present in members of the neurogliaform cell (NGFC) class. Single NGFCs displayed small dendritic trees, and their characteristically dense axonal arborizations covered significant portions of the outer and middle one-thirds of the molecular layer, with frequent axonal projections across the fissure into the CA1 and subicular regions. Typical NGFCs exhibited a late firing pattern with a ramp in membrane potential prior to firing action potentials, and single spikes in NGFCs evoked biphasic, prolonged GABA(A) and GABA(B) postsynaptic responses in GCs. In addition to providing dendritic GABAergic inputs to GCs, NGFCs also formed chemical synapses and gap junctions with various molecular layer interneurons, including other NGFCs. NGFCs received low-frequency spontaneous synaptic events, and stimulation of perforant path fibers revealed direct, facilitating synaptic inputs from the entorhinal cortex. Taken together, these results indicate that NGFCs form an integral part of the local molecular layer microcircuitry generating feed-forward inhibition and provide a direct GABAergic pathway linking the dentate gyrus to the CA1 and subicular regions through the hippocampal fissure.
| S-EPMC4015525 | biostudies-literature
Project description:BackgroundDevelopmental hypothyroidism impairs learning and memory in offspring, which depend on extensive neuronal circuits in the entorhinal cortex, together with the hippocampus and neocortex. The entorhinal-dentate gyrus pathway is the main entrance of memory circuits. We investigated whether developmental hypothyroidism impaired the morphological development of the entorhinal-dentate gyrus pathway.MethodsWe examined the structure and function of the entorhinal-dentate gyrus pathway in response to developmental hypothyroidism induced using 2-mercapto-1-methylimidazole.Results1,1´-Dioctadecyl-3,3,3´,3´-tetramethylindocarbocyanine perchlorate tract tracing indicated that entorhinal axons showed delayed growth in reaching the outer molecular layer of the dentate gyrus at postnatal days 2 and 4 in hypothyroid conditions. The proportion of fibers in the outer molecular layer was significantly smaller in the hypothyroid group than in the euthyroid group at postnatal day 4. At postnatal day 10, the pathway showed a layer-specific distribution in the outer molecular layer, similar to the euthyroid group. However, the projected area of entorhinal axons was smaller in the hypothyroid group than in the euthyroid group. An electrophysiological examination showed that hypothyroidism impaired the long-term potentiation of the perforant and the cornu ammonis 3-cornu ammonis 1 pathways. Many repulsive axon guidance molecules were involved in the formation of the entorhinaldentate gyrus pathway. The hypothyroid group had higher levels of erythropoietin-producing hepatocyte ligand A3 and semaphorin 3A than the euthyroid group.ConclusionWe demonstrated that developmental hypothyroidism might influence the development of the entorhinal-dentate gyrus pathway, contributing to impaired long-term potentiation. These findings improve our understanding of neural mechanisms for memory function.
| S-EPMC9081305 | biostudies-literature
Project description:BACE1 is validated as Alzheimer's ?-secretase and a therapeutic target for Alzheimer's disease. In examining BACE1-null mice, we discovered that BACE1 deficiency develops abnormal clusters of immature neurons, forming doublecortin-positive neuroblasts, in the developing dentate gyrus, mainly in the subpial zone (SPZ). Such clusters were rarely observed in wild-type SPZ and not reported in other mouse models. To understand their origins and fates, we examined how neuroblasts in BACE1-null SPZ mature and migrate during early postnatal development. We show that such neuroblasts are destined to form Prox1-positive granule cells in the dentate granule cell layer, and mainly mature to form excitatory neurons, but not inhibitory neurons. Mechanistically, higher levels of reelin potentially contribute to abnormal neurogenesis and timely migration in BACE1-null SPZ. Altogether, we demonstrate that BACE1 is a critical regulator in forming the dentate granule cell layer through timely maturation and migration of SPZ neuroblasts.
| S-EPMC5511112 | biostudies-literature