Browse
Submit Data
Databases
API
Help

Dataset Information

18 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Somatostatin interneurons activated by 5-HT_2A receptor suppress slow oscillations in medial entorhinal cortex.

ABSTRACT: Serotonin (5-HT) is one of the major neuromodulators present in the mammalian brain and has been shown to play a role in multiple physiological processes. The mechanisms by which 5-HT modulates cortical network activity, however, are not yet fully understood. We investigated the effects of 5-HT on slow oscillations (SOs), a synchronized cortical network activity universally present across species. SOs are observed during anesthesia and are considered to be the default cortical activity pattern. We discovered that (±)3,4-methylenedioxymethamphetamine (MDMA) and fenfluramine, two potent 5-HT releasers, inhibit SOs within the entorhinal cortex (EC) in anesthetized mice. Combining opto- and pharmacogenetic manipulations with in vitro electrophysiological recordings, we uncovered that somatostatin-expressing (Sst) interneurons activated by the 5-HT_2A receptor (5-HT_2AR) play an important role in the suppression of SOs. Since 5-HT_2AR signaling is involved in the etiology of different psychiatric disorders and mediates the psychological effects of many psychoactive serotonergic drugs, we propose that the newly discovered link between Sst interneurons and 5-HT will contribute to our understanding of these complex topics.

SUBMITTER: de Filippo R

PROVIDER: S-EPMC8016478 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Parvalbumin and Somatostatin Interneurons Control Different Space-Coding Networks in the Medial Entorhinal Cortex.

Project description:The medial entorhinal cortex (MEC) contains several discrete classes of GABAergic interneurons, but their specific contributions to spatial pattern formation in this area remain elusive. We employed a pharmacogenetic approach to silence either parvalbumin (PV)- or somatostatin (SOM)-expressing interneurons while MEC cells were recorded in freely moving mice. PV-cell silencing antagonized the hexagonally patterned spatial selectivity of grid cells, especially in layer II of MEC. The impairment was accompanied by reduced speed modulation in colocalized speed cells. Silencing SOM cells, in contrast, had no impact on grid cells or speed cells but instead decreased the spatial selectivity of cells with discrete aperiodic firing fields. Border cells and head direction cells were not affected by either intervention. The findings point to distinct roles for PV and SOM interneurons in the local dynamics underlying periodic and aperiodic firing in spatially modulated cells of the MEC. VIDEO ABSTRACT.

| S-EPMC5651217 | biostudies-literature

Somatostatin expressing GABAergic interneurons in the medial entorhinal cortex preferentially inhibit layer<sub>III-V</sub> pyramidal cells.

Project description:GABA released from heterogeneous types of interneurons acts in a complex spatio-temporal manner on postsynaptic targets in the networks. In addition to GABA, a large fraction of GABAergic cells also express neuromodulator peptides. Somatostatin (SOM) containing interneurons, in particular, have been recognized as key players in several brain circuits, however, the action of SOM and its downstream network effects remain largely unknown. Here, we used optogenetics, electrophysiologic, anatomical and behavioral experiments to reveal that the dendrite-targeting, SOM+ GABAergic interneurons demonstrate a unique layer-specific action in the medial entorhinal cortex (MEC) both in terms of GABAergic and SOM-related properties. We show that GABAergic and somatostatinergic neurotransmission originating from SOM+ local interneurons preferentially inhibit layerIII-V pyramidal cells, known to be involved in memory formation. We propose that this dendritic GABA-SOM dual inhibitory network motif within the MEC serves to selectively modulate working-memory formation without affecting the retrieval of already learned spatial navigation tasks.

| S-EPMC7728756 | biostudies-literature

GABAergic projections from the medial septum selectively inhibit interneurons in the medial entorhinal cortex.

Project description:The medial septum (MS) is required for theta rhythmic oscillations and grid cell firing in the medial entorhinal cortex (MEC). While GABAergic, glutamatergic, and cholinergic neurons project from the MS to the MEC, their synaptic targets are unknown. To investigate whether MS neurons innervate specific layers and cell types in the MEC, we expressed channelrhodopsin-2 in mouse MS neurons and used patch-clamp recording in brain slices to determine the response to light activation of identified cells in the MEC. Following activation of MS axons, we observed fast monosynaptic GABAergic IPSPs in the majority (>60%) of fast-spiking (FS) and low-threshold-spiking (LTS) interneurons in all layers of the MEC, but in only 1.5% of nonstellate principal cells (NSPCs) and in no stellate cells. We also observed fast glutamatergic responses to MS activation in a minority (<5%) of NSPCs, FS, and LTS interneurons. During stimulation of MS inputs at theta frequency (10 Hz), the amplitude of GABAergic IPSPs was maintained, and spike output from LTS and FS interneurons was entrained at low (25-60 Hz) and high (60-180 Hz) gamma frequencies, respectively. By demonstrating cell type-specific targeting of the GABAergic projection from the MS to the MEC, our results support the idea that the MS controls theta frequency activity in the MEC through coordination of inhibitory circuits.

| S-EPMC4261098 | biostudies-literature

Inhibition by Somatostatin Interneurons in Olfactory Cortex.

Project description:Inhibitory circuitry plays an integral role in cortical network activity. The development of transgenic mouse lines targeting unique interneuron classes has significantly advanced our understanding of the functional roles of specific inhibitory circuits in neocortical sensory processing. In contrast, considerably less is known about the circuitry and function of interneuron classes in piriform cortex, a paleocortex responsible for olfactory processing. In this study, we sought to utilize transgenic technology to investigate inhibition mediated by somatostatin (SST) interneurons onto pyramidal cells (PCs), parvalbumin (PV) interneurons, and other interneuron classes. As a first step, we characterized the anatomical distributions and intrinsic properties of SST and PV interneurons in four transgenic lines (SST-cre, GIN, PV-cre, and G42) that are commonly interbred to investigate inhibitory connectivity. Surprisingly, the distributions SST and PV cell subtypes targeted in the GIN and G42 lines were sparse in piriform cortex compared to neocortex. Moreover, two-thirds of interneurons recorded in the SST-cre line had electrophysiological properties similar to fast spiking (FS) interneurons rather than regular (RS) or low threshold spiking (LTS) phenotypes. Nonetheless, like neocortex, we find that SST-cells broadly inhibit a number of unidentified interneuron classes including putatively identified PV cells and surprisingly, other SST cells. We also confirm that SST-cells inhibit pyramidal cell dendrites and thus, influence dendritic integration of afferent and recurrent inputs to the piriform cortex. Altogether, our findings suggest that SST interneurons play an important role in regulating both excitation and the global inhibitory network during olfactory processing.

| S-EPMC4987344 | biostudies-literature

Impaired <i>In Vivo</i> Gamma Oscillations in the Medial Entorhinal Cortex of Knock-in Alzheimer Model.

Project description:The entorhinal cortex (EC) has bidirectional connections with the hippocampus and plays a critical role in memory formation and retrieval. EC is one of the most vulnerable regions in the brain in early stages of Alzheimer's disease (AD), a neurodegenerative disease with progressive memory impairments. Accumulating evidence from healthy behaving animals indicates gamma oscillations (30-100 Hz) as critical for mediating interactions in the circuit between EC and hippocampus. However, it is still unclear whether gamma oscillations have causal relationship with memory impairment in AD. Here we provide the first evidence that in vivo gamma oscillations in the EC are impaired in an AD mouse model. Cross-frequency coupling of gamma (30-100 Hz) oscillations to theta oscillations was reduced in the medial EC of anesthetized amyloid precursor protein knock-in (APP-KI) mice. Phase locking of spiking activity of layer II/III pyramidal cells to the gamma oscillations was significantly impaired. These data indicate that the neural circuit activities organized by gamma oscillations were disrupted in the medial EC of AD mouse model, and point to gamma oscillations as one of possible mechanisms for cognitive dysfunction in AD patients.

| S-EPMC5491963 | biostudies-literature

Multiple Running Speed Signals in Medial Entorhinal Cortex.

Project description:Grid cells in medial entorhinal cortex (MEC) can be modeled using oscillatory interference or attractor dynamic mechanisms that perform path integration, a computation requiring information about running direction and speed. The two classes of computational models often use either an oscillatory frequency or a firing rate that increases as a function of running speed. Yet it is currently not known whether these are two manifestations of the same speed signal or dissociable signals with potentially different anatomical substrates. We examined coding of running speed in MEC and identified these two speed signals to be independent of each other within individual neurons. The medial septum (MS) is strongly linked to locomotor behavior, and removal of MS input resulted in strengthening of the firing rate speed signal, while decreasing the strength of the oscillatory speed signal. Thus, two speed signals are present in MEC that are differentially affected by disrupted MS input.

| S-EPMC4976037 | biostudies-literature

Minute-scale oscillatory sequences in medial entorhinal cortex.

Project description: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.

| S-EPMC10781645 | biostudies-literature

A Characterization of the Electrophysiological and Morphological Properties of Vasoactive Intestinal Peptide (VIP) Interneurons in the Medial Entorhinal Cortex (MEC).

Project description:Circuit interactions within the medial entorhinal cortex (MEC) translate movement into a coherent code for spatial location. Entorhinal principal cells are subject to strong lateral inhibition, suggesting that a disinhibitory mechanism may drive their activation. Cortical Vasoactive Intestinal Peptide (VIP) expressing inhibitory neurons are known to contact other interneurons and excitatory cells and are thus capable of providing a local disinhibitory mechanism, yet little is known about this cell type in the MEC. To investigate the electrophysiological and morphological properties of VIP cells in the MEC, we use in vitro whole-cell patch-clamp recordings in VIPcre/tdTom mice. We report several gradients in electrophysiological properties of VIP cells that differ across laminae and along the dorsal-ventral MEC axis. We additionally show that VIP cells have distinct morphological features across laminae. Together, these results characterize the cellular and morphological properties of VIP cells in the MEC.

| S-EPMC8378838 | biostudies-literature

Complementary Modular Microcircuits of the Rat Medial Entorhinal Cortex.

Project description:The parahippocampal region is organized into different areas, with the medial entorhinal cortex (MEC), presubiculum and parasubiculum prominent in spatial memory. Here, we also describe a region at the extremity of the MEC and bordering the subicular complex, the medial-most part of the entorhinal cortex. While the subdivisions of hippocampus proper form more or less continuous cell sheets, the superficial layers of the parahippocampal region have a distinct modular architecture. We investigate the spatial distribution, laminar position, and putative connectivity of zinc-positive modules in layer 2 of the MEC of rats and relate them to the calbindin-positive patches previously described in the entorhinal cortex. We found that the zinc-positive modules are complementary to the previously described calbindin-positive patches. We also found that inputs from the presubiculum are directed toward the zinc-positive modules while the calbindin-positive patches received inputs from the parasubiculum. Notably, the dendrites of neurons from layers 3 and 5, positive for Purkinje Cell Protein 4 expression, overlap with the zinc modules. Our data thus indicate that these two complementary modular systems, the calbindin patches and zinc modules, are part of parallel information streams in the hippocampal formation.

| S-EPMC5385340 | biostudies-literature

Direct Medial Entorhinal Cortex Input to Hippocampal CA3 Is Crucial for eEF2K Inhibitor-Induced Neuronal Oscillations in the Mouse Hippocampus.

Project description:The hippocampal formation plays a vital role in memory formation and takes part in the control of the default neuronal network activity of the brain. It also represents an important structure to analyze drug-induced effects on subregion-specific synchronization of neuronal activity. However, the consequences of an altered functional state of synapses for subregion-specific synchronization of neuronal microcircuits remain to be fully understood. Therefore, we analyzed the direct interaction of neuronal microcircuits utilizing a genetically encoded calcium sensor (GCaMP6s) and local field potential (LFP) recording in acute hippocampal-entorhinal brain slices in response to a modulator of synaptic transmission. We observed that application of the eukaryotic elongation factor-2 kinase (eEF2K) inhibitor A484954, induced a large-scale synchronization of neuronal activity within different regions of the hippocampal formation. This effect was confirmed by the recording of extracellular LFPs. Further, in order to understand if the synchronized activity depended on interconnected hippocampal areas, we lesioned adjacent regions from each other. These experiments identified the origin of A484954-induced synchronized activity in the hippocampal CA3 subfield localized near the hilus of the dentate gyrus. Remarkably, the synchronization of neuronal activity in the hippocampus required an intact connection with the medial entorhinal cortex (MEC). In line with this observation, we detected an increase in neuronal activity in the MEC area after application of A484954. In summary, inhibition of eEF2K alters the intrinsic activity of interconnected neuronal microcircuits dominated by the MEC-CA3 afferents.

| S-EPMC7069380 | biostudies-literature