Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Two Functionally Distinct Serotonergic Projections into Hippocampus.

ABSTRACT: Hippocampus receives dense serotonergic input specifically from raphe nuclei. However, what information is carried by this input and its impact on behavior has not been fully elucidated. Here we used in vivo two-photon imaging of activity of hippocampal median raphe projection fibers in behaving male and female mice and identified two distinct populations: one linked to reward delivery and the other to locomotion. Local optogenetic manipulation of these fibers confirmed a functional role for these projections in the modulation of reward-induced behavior. The diverse function of serotonergic inputs suggests a key role in integrating locomotion and reward information into the hippocampal CA1.SIGNIFICANCE STATEMENT Information constantly flows in the hippocampus, but only some of it is captured as a memory. One potential process that discriminates which information should be remembered is concomitance with reward. In this work, we report a neuromodulatory pathway, which delivers reward signal as well as locomotion signal to the hippocampal CA1. We found that the serotonergic system delivers heterogeneous input that may be integrated by the hippocampus to support its mnemonic functions. It is dynamically involved in regulating behavior through interaction with the hippocampus. Our results suggest that the serotonergic system interacts with the hippocampus in a dynamic and behaviorally specific manner to regulate reward-related information processing.

SUBMITTER: Luchetti A

PROVIDER: S-EPMC7326349 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Functionally distinct high and low theta oscillations in the human hippocampus.

Project description:Based on rodent models, researchers have theorized that the hippocampus supports episodic memory and navigation via the theta oscillation, a ~4-10 Hz rhythm that coordinates brain-wide neural activity. However, recordings from humans have indicated that hippocampal theta oscillations are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in theta's function. To characterize human hippocampal theta, we examine the properties of theta oscillations throughout the anterior-posterior length of the hippocampus as neurosurgical subjects performed a virtual spatial navigation task. During virtual movement, we observe hippocampal oscillations at multiple frequencies from 2 to 14?Hz. The posterior hippocampus prominently displays oscillations at ~8-Hz and the precise frequency of these oscillations correlates with the speed of movement, implicating these signals in spatial navigation. We also observe slower ~3?Hz oscillations, but these signals are more prevalent in the anterior hippocampus and their frequency does not vary with movement speed. Our results converge with recent findings to suggest an updated view of human hippocampal electrophysiology. Rather than one hippocampal theta oscillation with a single general role, high- and low-frequency theta oscillations, respectively, may reflect spatial and non-spatial cognitive processes.

| S-EPMC7235253 | biostudies-literature

Two physically, functionally, and developmentally distinct peritoneal macrophage subsets.

Project description:The peritoneal cavity (PerC) is a unique compartment within which a variety of immune cells reside, and from which macrophages (MØ) are commonly drawn for functional studies. Here we define two MØ subsets that coexist in PerC in adult mice. One, provisionally called the large peritoneal MØ (LPM), contains approximately 90% of the PerC MØ in unstimulated animals but disappears rapidly from PerC following lipopolysaccharide (LPS) or thioglycolate stimulation. These cells express high levels of the canonical MØ surface markers, CD11b and F4/80. The second subset, referred to as small peritoneal MØ (SPM), expresses substantially lower levels of CD11b and F4/80 but expresses high levels of MHC-II, which is not expressed on LPM. SPM, which predominates in PerC after LPS or thioglycolate stimulation, does not derive from LPM. Instead, it derives from blood monocytes that rapidly enter the PerC after stimulation and differentiate to mature SPM within 2 to 4 d. Both subsets show clear phagocytic activity and both produce nitric oxide (NO) in response to LPS stimulation in vivo. However, their responses to LPS show key differences: in vitro, LPS stimulates LPM, but not SPM, to produce NO; in vivo, LPS stimulates both subsets to produce NO, albeit with different response patterns. These findings extend current models of MØ heterogeneity and shed new light on PerC MØ diversity, development, and function. Thus, they introduce a new context for interpreting (and reinterpreting) data from ex vivo studies with PerC MØ.

| S-EPMC2823920 | biostudies-literature

Intraspinal serotonergic neurons consist of two, temporally distinct populations in developing zebrafish.

Project description:Zebrafish intraspinal serotonergic neuron (ISN) morphology and distribution have been examined in detail at different ages; however, some aspects of the development of these cells remain unclear. Although antibodies to serotonin (5-HT) have detected ISNs in the ventral spinal cord of embryos, larvae, and adults, the only tryptophan hydroxylase (tph) transcript that has been described in the spinal cord is tph1a. Paradoxically, spinal tph1a is only expressed transiently in embryos, which brings the source of 5-HT in the ISNs of larvae and adults into question. Because the pet1 and tph2 promoters drive transgene expression in the spinal cord, we hypothesized that tph2 is expressed in spinal cords of zebrafish larvae. We confirmed this hypothesis through in situ hybridization. Next, we used 5-HT antibody labeling and transgenic markers of tph2-expressing neurons to identify a transient population of ISNs in embryos that was distinct from ISNs that appeared later in development. The existence of separate ISN populations may not have been recognized previously due to their shared location in the ventral spinal cord. Finally, we used transgenic markers and immunohistochemical labeling to identify the transient ISN population as GABAergic Kolmer-Agduhr double-prime (KA?) neurons. Altogether, this study revealed a novel developmental paradigm in which KA? neurons are transiently serotonergic before the appearance of a stable population of tph2-expressing ISNs.

| S-EPMC4823180 | biostudies-literature

Pioneer glutamatergic cells develop into a morpho-functionally distinct population in the juvenile CA3 hippocampus.

Project description:The developing CA3 hippocampus is comprised by highly connected hub neurons that are particularly effective in achieving network synchronization. Functional hub neurons were shown to be exclusively GABAergic, suggesting that the contribution of glutamatergic neurons to physiological synchronization processes at early postnatal stages is minimal. However, without fast GABAergic transmission, a different situation may prevail. In the adult CA3, blocking fast GABAergic transmission induces the generation of network bursts that can be triggered by the stimulation of single pyramidal neurons. Here we revisit the network function of CA3 glutamatergic neurons from a developmental viewpoint, without fast GABAergic transmission. We uncover a sub-population of early-generated glutamatergic neurons that impacts network dynamics when stimulated in the juvenile hippocampus. Additionally, this population displays characteristic morpho-physiological features in the juvenile and adult hippocampus. Therefore, the apparently homogeneous glutamatergic cell population likely displays a morpho-functional diversity rooted in temporal embryonic origins.

| S-EPMC3535425 | biostudies-literature

Protocadherin-?C2 is required for diffuse projections of serotonergic axons.

Project description:Serotonergic axons extend diffuse projections throughout various brain areas, and serotonergic system disruption causes neuropsychiatric diseases. Loss of the cytoplasmic region of protocadherin-? (Pcdh-?) family proteins, products of the diverse clustered Pcdh genes, causes unbalanced distributions (densification and sparsification) of serotonergic axons in various target regions. However, which Pcdh-? member(s) are responsible for the phenotype is unknown. Here we demonstrated that Pcdh-?C2 (?C2), a Pcdh-? isoform, was highly expressed in serotonergic neurons, and was required for normal diffusion in single-axon-level analyses of serotonergic axons. The loss of ?C2 from serotonergic neurons, but not from their target brain regions, led to unbalanced distributions of serotonergic axons. Our results suggest that ?C2 expressed in serotonergic neurons is required for serotonergic axon diffusion in various brain areas. The ?C2 extracellular domain displays homophilic binding activity, suggesting that its homophilic interaction between serotonergic axons regulates axonal density via ?C2's cytoplasmic domain.

| S-EPMC5698425 | biostudies-literature

The two eIF4A helicases in Trypanosoma brucei are functionally distinct.

Project description:Protozoan parasites belonging to the family Trypanosomatidae are characterized by an unusual pathway for the production of mRNAs via polycistronic transcription and trans-splicing of a 5' capped mini-exon which is linked to the 3' cleavage and polyadenylation of the upstream transcript. However, little is known of the mechanism of protein synthesis in these organisms, despite their importance as agents of a number of human diseases. Here we have investigated the role of two Trypanosoma brucei homologues of the translation initiation factor eIF4A (in the light of subsequent experiments these were named as TbEIF4AI and TbEIF4AIII). eIF4A, a DEAD-box RNA helicase, is a subunit of the translation initiation complex eIF4F which binds to the cap structure of eukaryotic mRNA and recruits the small ribosomal subunit. TbEIF4AI is a very abundant predominantly cytoplasmic protein (over 1 x 10(5) molecules/cell) and depletion to approximately 10% of normal levels through RNA interference dramatically reduces protein synthesis one cell cycle following double-stranded RNA induction and stops cell proliferation. In contrast, TbEIF4AIII is a nuclear, moderately expressed protein (approximately 1-2 x 10(4) molecules/cell), and its depletion stops cellular proliferation after approximately four cell cycles. Ectopic expression of a dominant negative mutant of TbEIF4AI, but not of TbEIF4AIII, induced a slow growth phenotype in transfected cells. Overall, our results suggest that only TbEIF4AI is involved in protein synthesis while the properties and sequence of TbEIF4AIII indicate that it may be the orthologue of eIF4AIII, a component of the exon junction complex in mammalian cells.

| S-EPMC1459412 | biostudies-literature

Two phenotypically and functionally distinct microglial populations in adult zebrafish.

Project description:Microglia are the tissue-resident macrophages in the central nervous system and are critically involved in immune defense, neural development and function, and neuroinflammation. The versatility of microglia has long been attributed to heterogeneity. Recent studies have revealed possible heterogeneity in human but not in murine microglia, yet a firm demonstration linking microglial heterogeneity to functional phenotypes remains scarce. Here, we identified two distinct microglial populations in adult zebrafish that differ in morphology, distribution, development, and function. The predominant population, phagocytotic microglia, which expresses ccl34b.1, is broadly distributed, amoeboid in shape, highly mobile, and phagocytotic. The other white matter-enriched ccl34b.1- population, regulatory microglia, has ramified protrusions but has limited mobility and phagocytosis capability. These functional differences are further supported by distinct transcriptomes and responses to bacterial infection, where ccl34b.1+ microglia function in tissue clearance and ccl34b.1- microglia release immune regulators. Our study sheds light on the heterogeneity and functional diversification of microglia.

| S-EPMC7673811 | biostudies-literature

Adult-born granule cells mature through two functionally distinct states.

Project description:Adult-born granule cells (ABGCs) are involved in certain forms of hippocampus-dependent learning and memory. It has been proposed that young but functionally integrated ABGCs (4-weeks-old) specifically contribute to pattern separation functions of the dentate gyrus due to their heightened excitability, whereas old ABGCs (>8 weeks old) lose these capabilities. Measuring multiple cellular and integrative characteristics of 3- 10-week-old individual ABGCs, we show that ABGCs consist of two functionally distinguishable populations showing highly distinct input integration properties (one group being highly sensitive to narrow input intensity ranges while the other group linearly reports input strength) that are largely independent of the cellular age and maturation stage, suggesting that 'classmate' cells (born during the same period) can contribute to the network with fundamentally different functions. Thus, ABGCs provide two temporally overlapping but functionally distinct neuronal cell populations, adding a novel level of complexity to our understanding of how life-long neurogenesis contributes to adult brain function.

| S-EPMC4131194 | biostudies-literature

Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation.

Project description:The BubR1/Bub3 complex is an important regulator of chromosome segregation as it facilitates proper kinetochore-microtubule interactions and is also an essential component of the spindle assembly checkpoint (SAC). Whether BubR1/Bub3 localization to kinetochores in human cells stimulates SAC signalling or only contributes to kinetochore-microtubule interactions is debated. Here we show that two distinct pools of BubR1/Bub3 exist at kinetochores and we uncouple these with defined BubR1/Bub3 mutants to address their function. The major kinetochore pool of BubR1/Bub3 is dependent on direct Bub1/Bub3 binding and is required for chromosome alignment but not for the SAC. A distinct pool of BubR1/Bub3 localizes by directly binding to phosphorylated MELT repeats on the outer kinetochore protein KNL1. When we prevent the direct binding of BubR1/Bub3 to KNL1 the checkpoint is weakened because BubR1/Bub3 is not incorporated into checkpoint complexes efficiently. In conclusion, kinetochore localization supports both known functions of BubR1/Bub3.

| S-EPMC4963475 | biostudies-literature

Atg15 in <i>Saccharomyces cerevisiae</i> consists of two functionally distinct domains.

Project description:Autophagy is a cellular degradation system widely conserved among eukaryotes. During autophagy, cytoplasmic materials fated for degradation are compartmentalized in double membrane-bound organelles called autophagosomes. After fusing with the vacuole, their inner membrane-bound structures are released into the vacuolar lumen to become autophagic bodies and eventually degraded by vacuolar hydrolases. Atg15 is a lipase that is essential for disintegration of autophagic body membranes and has a transmembrane domain at the N-terminus and a lipase domain at the C-terminus. However, the roles of the two domains in vivo are not well understood. In this study, we found that the N-terminal domain alone can travel to the vacuole via the multivesicular body pathway, and that targeting of the C-terminal lipase domain to the vacuole is required for degradation of autophagic bodies. Moreover, we found that the C-terminal domain could disintegrate autophagic bodies when it was transported to the vacuole via the Pho8 pathway instead of the multivesicular body pathway. Finally, we identified H435 as one of the residues composing the putative catalytic triad and W466 as an important residue for degradation of autophagic bodies. This study may provide a clue to how the C-terminal lipase domain recognizes autophagic bodies to degrade them.

| S-EPMC8108511 | 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