Biology subjects

Kenney, J. W.

Publications and source records attributed to Kenney, J. W..

9 recordsLinked to original sources

bioRxiv2025

The effects of Arabian jasmine on zebrafish behavior depends on strain, sex, and personality

Jasminum sambac (L.) Aiton, commonly known as Arabian jasmine, is widely used in Thai traditional medicine for mental health ailments. While most studies in humans and animals find that Arabian jasmine reduces stress and anxiety, there are a handful of reports that it can oppose relaxation by increasing autonomic arousal. Using adult zebrafish, we sought to determine whether factors like strain, sex, and personality might contribute to the variable effects of J. sambac on anxiety-related behavior. The flowers of J. sambac were extracted by ultrasonic-assisted extraction with optimal air pressure. Headspace solid-phase microextraction with gas chromatography-mass spectrometry (HS-SPME-GC-MS) identified the main components in the Arabian jasmine flower extract, including linalool (an anxiolytic compound) and benzaldehyde. We fed three strains of zebrafish (AB, TL, and WIK) a gelatin pellet containing different concentrations of J. sambac (5-20 mg kg-1) and assessed 3-dimensional swim behavior in the novel tank and mirror biting tests. We found that in female AB fish, J. sambac resulted in a decrease in bottom distance during the novel tank test, consistent with an anxiogenic effect; there was no effect in WIK or TL fish. We also found that behavioral/personality type influenced the effects of J. sambac where shy AB females increased their percent explored, consistent with an anxiolytic effect. Thus, we find that sex, genetics, and personality interact to influence the anxiety-related effects of Arabian jasmine suggesting that these factors may contribute to the opposing effects of Arabian jasmine reported in the literature.

animal behavior and cognition↗

bioRxiv2025

Individual differences in fear memory expression engage distinct functional brain networks

Fearful stimuli elicit a mix of active (e.g., evasion) and passive (e.g., freezing) behaviors in a wide range of species, including zebrafish (Danio rerio). How these different responses are encoded in the brain, and the extent to which individuals vary in their fear responses, is not clear. To investigate this, we first developed a contextual fear conditioning paradigm in adult zebrafish where fish associate a specific tank with an aversive pheromone, conspecific alarm substance (CAS). We collected data from over 300 fish across four different strains (AB, TU, TL, and WIK) and both sexes finding that, as expected, fish exhibit a mix of active and passive responses during CAS exposure and during memory expression. We also found that behavior fell into four distinct groups: non-reactive, evaders, evading freezers, and freezers, with the evading freezer and freezer groups most clearly associated with memory formation. Background strain and sex also influenced how fish respond to CAS, with males more likely to increase evasive behaviors in response to CAS and the TU strain more likely to be non-reactive during recall. Finally, using whole-brain activity mapping, we identified the brain regions associated with active and passive fear responses during memory expression and how the functional brain networks of evading freezers and freezers differed. Freezing behavior was associated with widespread neural activity that was particularly strong in the cerebellum, reticular formation, and parts of the telencephalon associated with olfactory processing. Evasive behavior was associated with an increase in the activity of visual threat detection and a decrease in the activity of brain regions related to foraging and navigation. Network analysis revealed that animals with high freezing and low evasion (i.e., freezers) had strong interactions between the pallium and cerebellum as well as strong interconnectivity between visual (pretectal) and thalamic analog (preglomerular) nuclei. Animals that mix freezing with evasive behaviors (i.e., evading freezers) had higher subpallial connectivity to regions involved in autonomic function and stress responses such as the hypothalamus and preoptic areas.

neuroscience↗

bioRxiv2024

Whole-brain mapping in adult zebrafish and identification of a novel tank test functional connectome

Identifying general principles of brain function requires the study of structure-function relationships in a variety of species. Zebrafish have recently gained prominence as a model organism in neuroscience, yielding important insights into vertebrate brain function. Although methods have been developed for mapping neural activity in larval animals, we lack similar techniques for adult zebrafish that have the advantage of a fully developed neuroanatomy and larger behavioral repertoire. Here, we describe a pipeline built around open-source tools for whole-brain activity mapping in freely swimming adult zebrafish. Our pipeline combines recent advances in histology, microscopy, and machine learning to capture cfos activity across the entirety of the adult brain. Images captured using light-sheet microscopy are registered to the recently created adult zebrafish brain atlas (AZBA) for automated segmentation using advanced normalization tools (ANTs). We used our pipeline to measure brain activity after zebrafish were subject to the novel tank test. We found that cfos levels peaked 15 minutes following behavior and that several regions containing serotoninergic, dopaminergic, noradrenergic, and cholinergic neurons were active during exploration. Finally, we generated a novel tank test functional connectome. Functional network analysis revealed that several regions of the medial ventral telencephalon form a cohesive sub-network during exploration. We also found that the anterior portion of the parvocellular preoptic nucleus (PPa) serves as a key connection between the ventral telencephalon and many other parts of the brain. Taken together, our work enables whole-brain activity mapping in adult zebrafish for the first time while providing insight into neural basis for the novel tank test.

animal behavior and cognition↗

bioRxiv2024

Individual differences in the boldness of female zebrafish are associated with alterations in serotonin function.

One of the most prevalent axes of behavioral variation in both humans and animals is risk taking, where individuals that are more willing to take risk are characterized as bold while those that are more reserved as shy. Brain monoamines (i.e., serotonin, dopamine, and norepinephrine) have been found to play a role in a variety of behaviors related to risk taking. Genetic variation related to monoamine function have also been linked to personality in both humans and animals. Using zebrafish, we investigated the relationship between monoamine function and boldness behavior during exploration of a novel tank. We found a sex-specific correlation between serotonin metabolism (5-HIAA:5-HT ratio) and boldness that was limited to female animals; there were no relationships between boldness and dopamine or norepinephrine. To probe differences in serotonergic function, we administered a serotonin reuptake inhibitor, escitalopram, to bold and shy fish, and assessed their exploratory behavior. We found that escitalopram had opposing effects on thigmotaxis in female animals with bold fish spending more time near the center of the tank and shy fish spent more time near the periphery. Taken together, our findings suggest that variation in serotonergic function makes sex-specific contributions to individual differences in risk taking behavior.

neuroscience↗

bioRxiv2023

Aging in zebrafish is associated with reduced locomotor activity and strain-dependent changes in predator avoidance behaviors related to anxiety.

Aging is associated with a wide range of physiological and behavioral changes in many species. Like humans, zebrafish exhibit gradual senescence, and thus may be a useful model organism for identifying evolutionarily conserved mechanisms related to aging. Here, we compared behavior in the novel tank test of young (6-month-old) and middle aged (12-month-old) zebrafish from two strains (TL and TU) and both sexes. We find that this modest age difference results in a reduction in locomotor activity and strain dependent changes in predator avoidance behaviors related to anxiety. Older TL fish have an elevation in bottom dwelling whereas older TU fish have a decrease in thigmotaxis. We found no consistent effects of age on either short-term (within session) or long-term (1 day later) habituation to the novel tank. Our findings support the use of zebrafish for the study of how age affects locomotion and how genetics interacts with age to alter the regulation of emotional behaviors in response to novelty.

animal behavior and cognition↗

bioRxiv2022

A gelatin-based feed for individually tailored drug delivery to adult zebrafish

Current approaches to drug delivery in adult zebrafish have significant limitations such as need for confinement, anesthesia, and/or dosing that is not based on body weight. To circumvent these challenges, we developed a non-invasive gelatin-based feed that is easily pipette into individually tailored morsels according to weight. Our feed was readily eaten by zebrafish (< 1 minute) with minimal leaching of compound (< 5%) when placed in water. We used our feed to deliver an NMDAR antagonist (MK-801, 4 mg/kg) prior to exposure to a novel tank. Consistent with prior work, we found that MK-801 caused a decrease in predator-avoidance/anxiety-like behaviors. We also found that MK-801 increased locomotion in male fish, but not females. Our simple, easy to prepare, and individually tailored gelatin-based feed now brings pharmacological manipulations of adult zebrafish in line with best practices used in other vertebrate model organisms.

pharmacology and toxicology↗

bioRxiv2022

Beyond bold versus shy: Zebrafish exploratory behavior falls into several behavioral clusters and is influenced by strain and sex

Consistent individual differences in exploratory behavior have been found across a range of taxa, including zebrafish, and are thought to contribute to evolutionary fitness. Animals that explore more of a novel environment, and visit areas of high predation risk, are considered bold, whereas animals with the opposite pattern of behavior are considered shy. Here, we examined whether this bimodal characterization of bold versus shy adequately captures the breadth of exploratory behavior exhibited by zebrafish or if, instead, behavior falls into multiple distinct behavioral subtypes. To identify the presence of behavioral subtypes, we applied unsupervised machine learning to behaviors extracted from three-dimensional swim traces from over 400 adult zebrafish across four strains (AB, TL, TU, and WIK) and both sexes. We found that behavior stratified into four distinct clusters. These included previously described bold and shy behavior as well as two new behavioral types: wall-huggers and active explorers. Consistent with prior work that found individual differences to be stable across time and influenced by biological factors like genetics and sex, the behavioral subtypes we identified were stable for up to 10 weeks and were influenced by the strain and sex of the animals. Taken together, our work suggests that individual differences in zebrafish exploratory behavior goes beyond bold versus shy and exhibits greater complexity than is typically assumed.

animal behavior and cognition↗

bioRxiv2021

AZBA: A 3D Adult Zebrafish Brain Atlas for the Digital Age

Zebrafish have made significant contributions to our understanding of the vertebrate brain and the neural basis of behavior, earning a place as one of the most widely used model organisms in neuroscience. Their appeal arises from the marriage of low cost, early life transparency, and ease of genetic manipulation with a behavioral repertoire that becomes more sophisticated as animals transition from larvae to adults. To further enhance the use of adult zebrafish, we created the first fully segmented three-dimensional digital adult zebrafish brain atlas (AZBA). AZBA was built by combining tissue clearing, light-sheet fluorescence microscopy, and three-dimensional image registration of nuclear and antibody stains. These images were used to guide segmentation of the atlas into over 200 neuroanatomical regions comprising the entirety of the adult zebrafish brain. As an open source, online azba.wayne.edu), updatable digital resource, AZBA will significantly enhance the use of adult zebrafish in furthering our understanding of vertebrate brain function in both health and disease.

neuroscience↗

bioRxiv2020

Changes in the functional connectome and behavior after exposure to chronic stress and increasing neurogenesis

Addition of new neurons to the dentate gyrus might change the activity of neural circuitry in the areas which the hippocampus projects to. The size of the hippocampus and the number of adult newborn granule cells are decreased by unpredictable chronic mild stress (UCMS). Additionally, one of the notable effects of chronic stress is the induction of {Delta}FosB, an unusually stable transcription factor which accumulates over time in several brain areas. This accumulation has been observed in many animal models of depression and it could have a protective role against stress, but no studies so far have explored how a specific increase in neurogenesis might regulate the induction and which brain networks might be predominately affected. We attempted to investigate the role of increasing adult hippocampal neurogenesis on stress-related behavior and the functional brain circuitry involved in mice exposed to UCMS. We used iBax mice, in which the pro-apoptotic gene Bax can be selectively ablated in neural stem cells, therefore inducibly enhancing survival of newborn neurons after tamoxifen administration. The animals were exposed to UCMS for 9 weeks and treated with tamoxifen in week 3 after the beginning of UCMS. In week 8, they were submitted to a battery of behavioral tests to assess depressive-like and anxiety-like behavior. In week 9, blood was collected to assess basal corticosterone levels, and the animals were sacrificed and their brain collected for {Delta}FosB immunohistochemistry. Brain-wide maps of {Delta}FosB expression were constructed and graph theoretical analyses were used to study the changes in brain networks after stress. UCMS induced negative correlations between the lateral entorhinal cortex and both the hippocampal structures and the nucleus accumbens in the VEH-treated mice, which were not present in other groups. Ranking nodes by degree reveals a strong thalamic-cortical signature in both non-stress (NS) groups. Exposure to UCMS seems to induce activity in thalamic areas and cerebral nuclei, with a different signature in the UCMS TAM group, which seems to completely "disengage" the neocortex and has most of its nodes with the most connections in the thalamic areas.

neuroscience↗