Biology subjects

Donaldson, Z.

Publications and source records attributed to Donaldson, Z..

6 recordsLinked to original sources

bioRxiv2024

Aging leads to sex-dependent effects on pair bonding and increased number of oxytocin-producing neurons in monogamous prairie voles

Pair bonds powerfully modulate health, which becomes particularly important when facing the detrimental effects of aging. To examine the impact of aging on relationship formation and response to loss, we examined behavior in 6-, 12-, and 18-month male and female prairie voles, a monogamous species that forms mating-based pair bonds. We found that older males (18-months) bonded quicker than younger voles, while similarly aged female voles increased partner directed affiliative behaviors. Supporting sex differences in bonding behaviors, we found that males were more likely to sample both partner and novel voles while females were more likely to display partner preference during the initial 20 minutes of the test. Using partner separation to study loss, we observed an erosion of partner preference only in 12-month females, but an overall decrease in partner-directed affiliation in females across all groups, but not in males. Finally, we found that the number of oxytocin, but not vasopressin, cells in the paraventricular hypothalamus increased during aging. These results establish prairie voles as a novel model to study the effects of normal and abnormal aging on pair bonding. HighlightsO_LI18-month male voles demonstrate accelerated bond formation C_LIO_LI18-month female voles increase partner-directed huddling after 2 wks C_LIO_LIBonds erode faster in 12-month female voles after partner separation C_LIO_LIFemale behavior from partner preference tests is reflected in free interaction C_LIO_LIThe number of paraventricular hypothalamus oxytocin cells increase during aging C_LI

neuroscience↗

bioRxiv2023

PhAT: A flexible open-source GUI-driven toolkit for photometry analysis

Photometry approaches detect sensor-mediated changes in fluorescence as a proxy for rapid molecular changes within the brain. As a flexible technique with a relatively low cost to implement, photometry is rapidly being incorporated into neuroscience laboratories. While multiple data acquisition systems for photometry now exist, robust analytical pipelines for the resulting data remain limited. Here we present the Photometry Analysis Toolkit (PhAT) - a free open source analysis pipeline that provides options for signal normalization, incorporation of multiple data streams to align photometry data with behavior and other events, calculation of event-related changes in fluorescence, and comparison of similarity across fluorescent traces. A graphical user interface (GUI) enables use of this software without prior coding knowledge. In addition to providing foundational analytical tools, PhAT is designed to readily incorporate community-driven development of new modules for more bespoke analyses, and data can be easily exported to enable subsequent statistical testing and/or code-based analyses. In addition, we provide recommendations regarding technical aspects of photometry experiments including sensor selection and validation, reference signal considerations, and best practices for experimental design and data collection. We hope that the distribution of this software and protocol will lower the barrier to entry for new photometry users and improve the quality of collected data, increasing transparency and reproducibility in photometry analyses. Basic Protocol 1: Software Environment Installation Basic Protocol 2: GUI-driven Fiber Photometry Analysis Basic Protocol 3: Adding Modules

neuroscience↗

bioRxiv2022

Nucleus accumbens dopamine release reflects the selective nature of pair bonds

In monogamous species, prosocial behaviors directed towards partners are dramatically different from those directed towards unknown individuals and potential threats. Dopamine release in the nucleus accumbens plays an important role in guiding social behavior, however, its role in real time social decision making in a monogamous species remains largely unknown. We used monogamous prairie voles to investigate how dopamine release differs in voles when seeking and interacting with a pair bonded partner or a novel vole. Employing the sub-second temporal resolution of the fluorescent biosensor, GRABDA, during a social operant task, we found that partner seeking, anticipation, and interaction resulted in more dopamine release than the same events directed towards a novel vole. Furthermore, partner-elicited dopamine release decreases after prolonged partner separation. Thus, differences in partner- and novel-elicited dopamine release reflect the selective nature of pair bonds and may drive the social behaviors that reinforce and cement bonds over time, eroding after partner loss to facilitate new bond formation.

neuroscience↗

bioRxiv2021

Sex differences in the reward value of familiar mates in prairie voles

The rewarding properties of social interactions facilitate relationship formation and maintenance. Prairie voles are one of the few laboratory species that form selective relationships, manifested as "partner preferences" for familiar partners versus strangers. While both sexes exhibit strong partner preferences, this similarity in outward behavior likely results from sex-specific neurobiological mechanisms. We recently used operant conditioning to demonstrate that females work harder for access to a familiar versus unfamiliar conspecific of either sex, while males worked equally hard for access to any female, indicating a key sex difference in social motivation. As tests were performed with one social target at a time, males might have experienced a ceiling effect, and familiar females might be more relatively rewarding in a choice scenario. Here we performed a social choice operant task in which voles could repeatedly lever-press to gain temporary access to either the chamber containing their mate or one containing a novel opposite-sex vole. Females worked hardest to access their mate, while males pressed at similar rates for either female. Individual male behavior was heterogeneous, congruent with multiple mating strategies in the wild. Voles exhibited preferences for favorable over unfavorable environments in a non-social operant task, indicating that lack of social preference does not reflect lack of discrimination between chambers. Oxytocin receptor genotype at the intronic SNP NT213739 replicated a prior association with stranger-directed aggression within the test. These findings suggest that convergent preference behavior in male and female voles results from sex-divergent pathways, particularly in the realm of social motivation.

animal behavior and cognition↗

bioRxiv2019

A neuronal signature for monogamous reunion

Pair bond formation depends vitally on neuromodulatory signaling within the nucleus accumbens, but the neuronal dynamics underlying this behavior remain unclear. Using in vivo Ca2+ imaging in monogamous prairie voles, we found that pair bonding does not elicit differences in overall nucleus accumbens Ca2+ activity. Instead, we identified distinct neuronal ensembles in this region recruited during approach to either a partner or novel vole. The partner-approach neuronal ensemble increased in size following bond formation and differences in the size of approach ensembles for partner and novel voles predicts bond strength. In contrast, neurons comprising departure ensembles do not change over time and are not correlated with bond strength indicating that ensemble plasticity is specific to partner approach. Further, the neurons comprising partner and novel approach ensembles are non-overlapping while departure ensembles are more overlapping than chance, which may reflect another key feature of approach ensembles. We posit that the features of the partner approach ensemble and its expansion upon bond formation make it a potential key substrate underlying bond formation and maturation.\n\nHighlightsO_LIWe performed in vivo Ca2+ in the nucleus accumbens of pair bonded prairie voles\nC_LIO_LIOverall nucleus accumbens activity did not differ during partner versus stranger interaction\nC_LIO_LIDistinct approach neurons exist for the partner and for the stranger\nC_LIO_LIPartner-approach ensemble increases as partner preference emerges\nC_LIO_LIWe identify a putative neuronal substrate underlying bond formation and maturation\nC_LI

neuroscience↗

bioRxiv2018

Functional interrogation of a depression-related serotonergic SNP, rs6295, using a humanized mouse model

The serotonin 1A receptor (5-HT1A) system has been extensively implicated in modulating mood and behavior. Notably, 5-HT1A levels in humans display remarkable variation and differences in receptor levels have been linked with a variety of psychiatric disorders. Further, manipulation of receptor levels in mice suggests that changes in receptor levels that model existing human variation are sufficient to drive behavioral alterations. As a result, genetic mechanisms that modulate human 5-HT1A levels may be important for explaining individual differences in mood and behavior, representing a potential source of psychiatric disease risk. One common genetic variant implicated in differential 5-HT1A levels is the G/C single nucleotide polymorphism (SNP), rs6295, located upstream of the human 5-HT1A gene. This SNP differentially binds the transcription factor, NUDR/Deaf1, leading to cell-type specific effects on transcription in vitro. To investigate the direct effects of this SNP in the heterogeneous cellular context of the brain, we generated humanized transgenic mice using a design that maximized the local transcriptional landscape of the human HTR1A gene while also controlling for effects of genomic insertion location. Expression of the human transgene in a 5-HT1A null mouse resulted in line-dependent expression of human 5-HT1A. The effect of rs6295 on protein levels and behavior similarly differed across lines, suggesting that the penetrance of rs6295 may depend upon background genetic factors. Together, this work confirms that relatively subtle differences in 5-HT1A levels can contribute to differences in behavior and highlights the challenges of modeling human non-coding genetic variation in mice.

neuroscience↗