scholarly journals Social Reactivation of Fear Engrams Enhances Recall and Reinstatement

2021 ◽  
Author(s):  
Abby Basya Finkelstein ◽  
Heloise Leblanc ◽  
Rebecca Cole ◽  
Troy Gallerani ◽  
Anahita Vieira ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Social Interactions ◽  
Social Environment ◽  
Social Stress ◽  
Social Experience ◽  
Social Experiences ◽  
Optogenetic Stimulation ◽  
Specific Enhancement ◽  
Context Specific ◽  
Stimulation Of

The power of one's social environment to modulate cognition is well documented, but the processes by which social experiences impact the cellular substrates of memory remain unknown. We show that social experience, but not physical stress, causes reactivation of fear engrams in the dentate gyrus of the hippocampus, and optogenetic stimulation of social ensembles containing these reactivated cells is sufficient to drive fearful behavior. This endogenous reactivation in the dentate gyrus during social stress is followed by a context-specific enhancement of fear recall and reinstatement. Our findings suggest that social interactions can reactivate pre-existing engrams and thereby strengthen discrete memories.

scholarly journals Chronic optogenetic stimulation of hippocampal engrams variably modulates social behaviors in mice

2020 ◽  
Author(s):  
Emily Doucette ◽  
Heloise Leblanc ◽  
Amy Monasterio ◽  
Christine Cincotta ◽  
Stephanie L. Grella ◽  
...  
Keyword(s):  
Social Interactions ◽  
Neural Activity ◽  
Social Behaviors ◽  
Behavioral Effects ◽  
Early Gene ◽  
Group Differences ◽  
Neural Responses ◽  
Chronic Stimulation ◽  
Optogenetic Stimulation ◽  
Stimulation Of

AbstractThe hippocampus processes both spatial-temporal information and emotionally salient experiences. To test the functional properties of discrete sets of cells in the dorsal dentate gyrus (dDG), we examined whether chronic optogenetic reactivation of these ensembles was sufficient to modulate social behaviors in mice. We found that chronic reactivation of dDG cells in male mice was sufficient to enhance social behaviors in a female exposure task when compared to pre-stimulation levels. However, chronic reactivation of these cells was not sufficient to modulate group differences in a separate subset of social behaviors, and multi-region analysis of neural activity did not yield detectable differences in immediate-early gene expression or neurogenesis, suggesting a dissociation between our chronic stimulation-induced behavioral effects and underlying neural responses. Together, our results demonstrate that chronic optogenetic stimulation of cells processing valent experiences enduringly and unidirectionally modulates social interactions between male and female mice.

scholarly journals 2429 Optogenetic stimulation of corticotropin-releasing hormone expressing neurons in Barrington’s nucleus recapitulates the social stress voiding phenotype in mice

2018 ◽  
Vol 2 (S1) ◽  
pp. 23-23
Author(s):  
Jason Van Batavia ◽  
Stephan Butler ◽  
Joanna Fesi ◽  
Rita Valentino ◽  
Stephen Zderic
Keyword(s):  
Social Stress ◽  
Bladder Capacity ◽  
Significant Rise ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Optogenetic Stimulation ◽  
Void Volumes ◽  
Voiding Postponement ◽  
Stimulation Of

OBJECTIVES/SPECIFIC AIMS: Voiding postponement is common cause of LUT dysfunction in which children void infrequently with large volumes. This condition is modeled in mice that are subjected to social stress who show decreased voiding frequency and increased voided volumes along with increases in corticotropin-releasing hormone (CRH) expression in Barrington’s nucleus (BN) (i.e., the pontine micturition center). Optogenetics is a technique to selectively stimulate cells or neurons of interest via light activated channel receptors [i.e., channel-2 rhodopsin (ChR2)]. Here we examined the effects of optogenetic manipulation of CRH BN neurons on the in vivo voiding phenotype and urodynamics in awake mice. We hypothesized that stimulating these neurons at higher frequencies (10–50 Hz) would lead to CRH-dependent alterations in voiding phenotype (i.e., larger voided volumes and longer intermicturition intervals. METHODS/STUDY POPULATION: Double transgenic mice expressing ChR2 in CRH cells were generated using the Cre-lox recombinase system and had fiberoptic probes implanted into BN at 8 weeks of age. The mice also underwent simultaneous catheter placement into the bladder for in vivo cystometry. In vivo cystometry before and during optogenetic stimulation at various frequencies was performed 5–7 days postoperatively. Saline was perfused at 10 µL/minute and baseline stable voiding cycles were established. Bladder capacity, threshold pressure, voiding pressure, and voided volume were recorded at baseline and at each optogenetic setting. In some mice, the protocol was repeated in the presence of CRH antagonist (NBI 30775). RESULTS/ANTICIPATED RESULTS: Fiberoptic stimulation (470 nm at 25 and 50 Hz) produced a significant rise in the intermicturition interval, bladder capacities and increased void volumes. This effect was especially pronounced in females in whom bladder capacity and intermicturition interval more than doubled at 50 Hz stimulation. Fluoroscopic images confirmed complete bladder emptying with each void. The increased bladder capacity at higher frequencies (25 and 50 Hz) was CRH-dependent as injection of a CRH antagonist (NBI 30775) blocked the optogenetic effect. Control non-double mice showed no effects from optogenetic stimulation. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggest that optogenetic stimulation of CRH-expressing neurons in BN at high frequency (25 and 50 Hz) inhibits micturition and recapitulates the voiding phenotype seen in socially stressed mice (large, infrequent voids). Lower frequencies of optogenetic stimulation (2 and 10 Hz) had no effects on cystometry parameters or voiding phenotype. In addition, females had a greater response to optogenetic stimulation compared with males with larger bladder capacities and longer intermicturition intervals. The changes in voiding phenotype seen were CRH dependent as blockage of the CRH receptor prevented changes in cystometry parameters with optogenetic stimulation. Further elucidation of these and other neural subpopulations in BN are warranted to understand micturition and how it may be manipulated in disease states such as voiding postponement and acute urinary retention.

scholarly journals Optogenetic stimulation of dentate gyrus engrams restores memory in Alzheimer's disease mice

Hippocampus ◽  
2017 ◽  
Vol 27 (10) ◽  
pp. 1110-1122 ◽  
Author(s):  
Jennifer N. Perusini ◽  
Stephanie A. Cajigas ◽  
Omid Cohensedgh ◽  
Sean C. Lim ◽  
Ina P. Pavlova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dentate Gyrus ◽  
Optogenetic Stimulation ◽  
Stimulation Of

scholarly journals Incerto-thalamic modulation of fear via GABA and dopamine

2021 ◽  
Author(s):  
Archana Venkataraman ◽  
Sarah C. Hunter ◽  
Maria Dhinojwala ◽  
Diana Ghebrezadik ◽  
JiDong Guo ◽  
...  
Keyword(s):  
Brain Regions ◽  
Zona Incerta ◽  
Dependent Manner ◽  
Post Traumatic Stress ◽  
Functional Roles ◽  
Functional Connections ◽  
Optogenetic Stimulation ◽  
Fear Generalization ◽  
Stimulation Of

AbstractFear generalization and deficits in extinction learning are debilitating dimensions of Post-Traumatic Stress Disorder (PTSD). Most understanding of the neurobiology underlying these dimensions comes from studies of cortical and limbic brain regions. While thalamic and subthalamic regions have been implicated in modulating fear, the potential for incerto-thalamic pathways to suppress fear generalization and rescue deficits in extinction recall remains unexplored. We first used patch-clamp electrophysiology to examine functional connections between the subthalamic zona incerta and thalamic reuniens (RE). Optogenetic stimulation of GABAergic ZI → RE cell terminals in vitro induced inhibitory post-synaptic currents (IPSCs) in the RE. We then combined high-intensity discriminative auditory fear conditioning with cell-type-specific and projection-specific optogenetics in mice to assess functional roles of GABAergic ZI → RE cell projections in modulating fear generalization and extinction recall. In addition, we used a similar approach to test the possibility of fear generalization and extinction recall being modulated by a smaller subset of GABAergic ZI → RE cells, the A13 dopaminergic cell population. Optogenetic stimulation of GABAergic ZI → RE cell terminals attenuated fear generalization and enhanced extinction recall. In contrast, optogenetic stimulation of dopaminergic ZI → RE cell terminals had no effect on fear generalization but enhanced extinction recall in a dopamine receptor D1-dependent manner. Our findings shed new light on the neuroanatomy and neurochemistry of ZI-located cells that contribute to adaptive fear by increasing the precision and extinction of learned associations. In so doing, these data reveal novel neuroanatomical substrates that could be therapeutically targeted for treatment of PTSD.

scholarly journals Involvement of MCH-oxytocin neural relay within the hypothalamus in murine nursing behavior

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoko Kato ◽  
Harumi Katsumata ◽  
Ayumu Inutsuka ◽  
Akihiro Yamanaka ◽  
Tatsushi Onaka ◽  
...  
Keyword(s):  
Mammalian Species ◽  
Virgin Female ◽  
Essential Elements ◽  
Hypothalamic Nucleus ◽  
Male Mice ◽  
Hypothalamic Area ◽  
Functional Roles ◽  
Genetic Ablation ◽  
Optogenetic Stimulation ◽  
Stimulation Of

AbstractMultiple sequential actions, performed during parental behaviors, are essential elements of reproduction in mammalian species. We showed that neurons expressing melanin concentrating hormone (MCH) in the lateral hypothalamic area (LHA) are more active in rodents of both sexes when exhibiting parental nursing behavior. Genetic ablation of the LHA-MCH neurons impaired maternal nursing. The post-birth survival rate was lower in pups born to female mice with congenitally ablated MCH neurons under control of tet-off system, exhibiting reduced crouching behavior. Virgin female and male mice with ablated MCH neurons were less interested in pups and maternal care. Chemogenetic and optogenetic stimulation of LHA-MCH neurons induced parental nursing in virgin female and male mice. LHA-MCH GABAergic neurons project fibres to the paraventricular hypothalamic nucleus (PVN) neurons. Optogenetic stimulation of PVN induces nursing crouching behavior along with increasing plasma oxytocin levels. The hypothalamic MCH neural relays play important functional roles in parental nursing behavior in female and male mice.

scholarly journals Dominance relationships and coalitionary aggression against conspecifics in female carrion crows

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Benedikt Holtmann ◽  
Julia Buskas ◽  
Matthew Steele ◽  
Kristaps Solokovskis ◽  
Jochen B. W. Wolf
Keyword(s):  
Social Interactions ◽  
Social Environment ◽  
Social Rank ◽  
Social Benefits ◽  
Same Sex ◽  
The Third ◽  
Dominance Relationships ◽  
Dominant Individual ◽  
The Individual

Abstract Cooperation is a prevailing feature of many animal systems. Coalitionary aggression, where a group of individuals engages in coordinated behaviour to the detriment of conspecific targets, is a form of cooperation involving complex social interactions. To date, evidence has been dominated by studies in humans and other primates with a clear bias towards studies of male-male coalitions. We here characterize coalitionary aggression behaviour in a group of female carrion crows consisting of recruitment, coordinated chase, and attack. The individual of highest social rank liaised with the second most dominant individual to engage in coordinated chase and attack of a lower ranked crow on several occasions. Despite active intervention by the third most highly ranked individual opposing the offenders, the attack finally resulted in the death of the victim. All individuals were unrelated, of the same sex, and naïve to the behaviour excluding kinship, reproduction, and social learning as possible drivers. Instead, the coalition may reflect a strategy of the dominant individual to secure long-term social benefits. Overall, the study provides evidence that members of the crow family engage in coordinated alliances directed against conspecifics as a possible means to manipulate their social environment.

Increase in extracellular dopamine levels during clozapine-induced potentiation in the hippocampal dentate gyrus of chronically prepared rabbits

2008 ◽  
Vol 86 (5) ◽  
pp. 249-256 ◽  
Author(s):  
Takashi Kubota ◽  
Itsuki Jibiki ◽  
Akira Ishikawa ◽  
Tomomi Kawamura ◽  
Sonoko Kurokawa ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Nmda Receptor ◽  
Dentate Gyrus ◽  
Negative Symptoms ◽  
Clinical Effect ◽  
Perforant Path ◽  
Hippocampal Dentate Gyrus ◽  
Extracellular Dopamine ◽  
Stimulation Of ◽  
Synaptic Responses

We previously found that 20 mg/kg clozapine i.p. potentiated the excitatory synaptic responses elicited in the dentate gyrus by single electrical stimulation of the perforant path in chronically prepared rabbits. We called this phenomenon clozapine-induced potentiation and proved that it was an NMDA receptor-mediated event. This potentiation is presumably related to clozapine’s clinical effect on negative symptoms and cognitive dysfunctions in schizophrenia. In the present study, to investigate the mechanisms underlying clozapine-induced potentiation, we examined whether extracellular dopamine and 5-HT levels changed during the potentiation by using a microdialysis technique in the dentate gyrus. The extracellular concentrations of dopamine and 5-HT levels were measured every 5 min during all experiments. Extracellular 5-HT levels did not change, but dopamine levels eventually increased significantly during clozapine-induced potentiation. The increase in the dopamine levels occurred almost simultaneously with the induction of clozapine-induced potentiation. These results suggest that clozapine-induced potentiation is at least partly attributable to a dopamine-mediated potentiation of excitatory synaptic transmission. The present study implies that such phenomena occur also in the perforant path–dentate gyrus pathway.

scholarly journals THE MECHANISM OF ANTIGENIC STIMULATION OF PRIMARY AND SECONDARY CLONAL PRECURSOR CELLS

1972 ◽  
Vol 136 (2) ◽  
pp. 241-260 ◽  
Author(s):  
Norman R. Klinman
Keyword(s):  
Serum Antibody ◽  
Precursor Cells ◽  
Antigenic Stimulation ◽  
Soluble Antigen ◽  
Antigen Receptors ◽  
Antigen Concentration ◽  
High Affinity ◽  
Specific Enhancement ◽  
Stimulation Of

Cell transfers to carrier-immunized irradiated mice have permitted an analysis of the in vitro stimulation of clonal precursors of anti-2,4-dinitrophenyl (DNP) antibody-producing cells derived from both immune and nonimmune mice. The results indicate that: (a) carrier-specific enhancement is obligatory for stimulation of primary precursor cells and increases both the size and number of detectable foci derived from secondary precursors. (b) This carrier-specific enhancement is most apparent in the stimulation of precursors of high-affinity antibody producer cells. (c) The antibody produced by primary foci, like that of secondary foci, appears homogeneous. (d) The frequency of clonal precursors in normal spleens is 38% that in spleens from mice 4–8 months after immunization, and the number of such precursors in normal spleens can be reduced fivefold by specific suppression of donor mice with soluble antigen. (e) The average of association constants of primary monofocal antibodies, like that of primary serum antibody produced in carrier-primed mice, is less than 10-fold lower than that of secondary clonal or serum antibody. (f) The affinity of primary monofocal antibodies shows a slight dependence on stimulating antigen concentration; however, a minimum threshold affinity consonant with stimulation is apparent. (g) Free hapten inhibits antigenic stimulation of primary precursor cells at a much lower concentration than is required for the inhibition of secondary precursors. These results are interpreted as indicating that (a) primary stimulation, like secondary stimulation, results from the selective stimulation by antigen of a population of cells differing from one another in their potential antibody product but each having only a single such product; (b) the antigen receptors of primary cells interact with antigen as if they are monovalent while receptors of secondary cells evidence multivalence; (c) antigenic stimulation appears to require both a relatively high affinity of receptors for bound antigen and an interlinking of receptors through such antigen; stimulation is thus seen as resulting from a stabilization of receptors within antigen-receptor aggregates to the cell surface; (d) T-cells appear to serve both in cross-linking antigens and in amplifying the size of stimulated clones.

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