Publications

Opposing, spatially-determined epigenetic forces impose restrictions on stochastic olfactory receptor choice

Bashkirova E.V., Klimpert N., Monahan K., Campbell C.E., Osinski J., Tan L., Schieren I., Pourmorady A., Stecky B., Barnea G., Xie X.S., Abdus-Saboor I., Shykind B.M., Marlin B.J., Gronostajski R.M., Fleischmann A., Lomvardas S.
(2023) eLife

  • Olfactory receptor (OR) choice represents an example of genetically hardwired stochasticity, where every olfactory neuron expresses one out of ~2000 OR alleles in the mouse genome in a probabilistic, yet stereotypic fashion. Here, we propose that topographic restrictions in OR expression are established in neuronal progenitors by two opposing forces: polygenic transcription and genomic silencing, both of which are influenced by dorsoventral gradients of transcription factors NFIA, B, and X. Polygenic transcription of OR genes may define spatially constrained OR repertoires, among which one OR allele is selected for singular expression later in development. Heterochromatin assembly and genomic compartmentalization of OR alleles also vary across the axes of the olfactory epithelium and may preferentially eliminate ectopically expressed ORs with more dorsal expression destinations from this ‘privileged’ repertoire. Our experiments identify early transcription as a potential ‘epigenetic’ contributor to future developmental patterning and reveal how two spatially responsive probabilistic processes may act in concert to establish deterministic, precise, and reproducible territories of stochastic gene expression.

Fear conditioning biases olfactory stem cell receptor fate

Liff C.W., Ayman Y.R., Jaeger E.C.B., Lee H.S., Kim A., Albarracin A.V., Marlin B.J.
(2023) eLife

  • The main olfactory epithelium initiates the process of odor encoding. Recent studies have demonstrated intergenerationally inherited changes in the olfactory system in response to fear conditioning, resulting in increases in olfactory receptor frequencies and altered responses to odors. We investigated changes in the morphology of the olfactory epithelium in response to an aversive stimulus. Here, we achieve volumetric cellular resolution to demonstrate that olfactory fear conditioning increases the number of odor-encoding neurons in mice that experience odor-shock conditioning (F0), as well as their offspring (F1). We provide evidence that increases in F0 were due to biased stem cell receptor choice. Thus, we reveal dynamic regulation of the olfactory epithelium receptor composition in response to olfactory fear conditioning, providing insight into the heritability of acquired phenotypes.

Integration of olfactory and auditory cues eliciting parental behavior

McRae B.R., Andreu, V., Marlin B.J.
(2023) Journal of Neuroendocrinology

  • Parental care is crucial for the survival of all mammalian species. Given the evolutionary importance of parenting, this behavioral repertoire must be supported by circuitry that is innate but also capable of learning and flexibility – adjusting to changing environmental demands. In rodents, parental care is triggered by the perception of cues emitted by a pup. Caregiver-pup interactions are often composed of multimodal sensory stimuli that require caregivers to integrate across sensory modalities. In this review, we focus on two sensory modalities essential for the parental experience: smell and hearing. We examine how smell and hearing are combined with other senses to identify offspring in need of care. Understanding how multimodal stimuli are integrated in the caregiver brain to inform parental behavior is an important step in understanding the circuitry that underlies this complex and crucial behavioral repertoire. In this review, we will discuss recent advances in the field of rodent parental behavior, highlighting studies that have begun to disentangle the neural circuitry that processes the multisensory cues that are involved in caregiver-offspring interactions.

Juneteenth in STEMM and the barriers to equitable science

Mays A., Byars-Winston, A., Hinton Jr. A, Marshall A.G., Kirabo A., August A., Marlin B.J., Riggs B., Tolbert B., Wanjalia C., Womack C., Evans C.S., Barnes C., Starbird C., Williams C., Reynolds C., Taabazuing C., Cameron C.E., Murray D.D., Applewhite D., Morton D.J., Lee D., Williams D.W., Lynch D., Brady D., Lynch E., Rutaganira F.U.N., Silva G.M., Shuler H., Saboor I.A., Davis J., Dzirasa K., Hammonds-Odie L., Reyes L., Sweetwyne M.T., McReynolds M.R., Johnson M.D.L., Smith N.A., Pittman N., Ajijola O.A., Smith Q., Robinson R.A.S., Lewis S.C., Murray S.A., Black S., Neal S.E., Andrisse S., Townsend S., Damo S.M., Griffith T.N., Lambert W.M., Clemons Jr. W.M.
(2023) Cell

  • We are 52 Black scientists. Here, we establish the context of Juneteenth in STEMM and discuss the barriers Black scientists face, the struggles they endure, and the lack of recognition they receive. We review racism’s history in science and provide institutional-level solutions to reduce the burdens on Black scientists.

Oxytocin neurons enable social transmission of maternal behaviour

Carcea I., Caraballo N.L., Marlin B.J., …Froemke R.C.
(2021) Nature

  • Maternal care, including by non-biological parents, is important for offspring survival. Oxytocin, which is released by the hypothalamic paraventricular nucleus (PVN), is a critical maternal hormone. In mice, oxytocin enables neuroplasticity in the auditory cortex for maternal recognition of pup distress. However, it is unclear how initial parental experience promotes hypothalamic signalling and cortical plasticity for reliable maternal care. Here we continuously monitored the behaviour of female virgin mice co-housed with an experienced mother and litter. This documentary approach was synchronized with neural recordings from the virgin PVN, including oxytocin neurons. These cells were activated as virgins were enlisted in maternal care by experienced mothers, who shepherded virgins into the nest and demonstrated pup retrieval. Virgins visually observed maternal retrieval, which activated PVN oxytocin neurons and promoted alloparenting. Thus rodents can acquire maternal behaviour by social transmission, providing a mechanism for adapting the brains of adult caregivers to infant needs via endogenous oxytocin.

Neuron Q&A: Bianca Jones Marlin

Marlin B.J.
(2021) Neuron

  • Bianca Jones Marlin draws inspiration for her work from people’s stories. In an interview with Neuron, she talks about overcoming the challenges of the past year—opening a new lab, caring for a young family, and gaining the strength to speak her truth and create the inclusive community academia strives for.

Racial and ethnic imbalance in neuroscience reference lists and intersections with gender

Bertolero M.A., Dworkin J.D., David S.U., Lloreda C.L., Srivastava P., Stiso J., Zhou D., Dzirasa K., Fair D.A., Kaczkurkin A.N., Marlin B.J., Shohamy D., Uddin L.Q., Zurn P., Bassett D.S
(2020) bioRxiv

  • Discrimination against racial and ethnic minority groups exists in the academy, and the associated biases impact hiring and promotion, publication rates, grant funding, and awards. Precisely how racial and ethnic bias impacts the manner in which the scientific community engages with the ideas of academics in minority groups has yet to be fully elucidated. Citations are a marker of such community engagement, as well as a currency used to attain career milestones. Here we assess the extent and drivers of racial and ethnic imbalance in the reference lists of papers published in five top neuroscience journals over the last 25 years. We find that reference lists tend to include more papers with a White person as first and last author than would be expected if race and ethnicity were unrelated to referencing. We show that this imbalance is driven largely by the citation practices of White authors, and is increasing over time even as the field diversifies. To further explain our findings, we examine co-authorship networks and find that while the network has become markedly more integrated in general, the current degree of segregation by race/ethnicity is greater now than it has been in the past. Citing further from oneself on the network is associated with greater balance, but White authors’ preferential citation of White authors remains even at high levels of network exploration. We also quantify the effects of intersecting identities, determining the relative costs of gender and race/ethnicity, and their combination in women of color. Our findings represent a call to scientists and journal editors of all disciplines to consider the ethics of citation practices, and actions to be taken in support of an equitable future.

The next 50 years of neuroscience

Altimus C.M.*, Marlin B.J.*…for Training Advisory Committee.
(2020) The Journal of Neuroscience

  • On the 50th anniversary of the Society for Neuroscience, we reflect on the remarkable progress that the field has made in understanding the nervous system, and look forward to the contributions of the next 50 years. We predict a substantial acceleration of our understanding of the nervous system that will drive the development of new therapeutic strategies to treat diseases over the course of the next five decades. We also see neuroscience at the nexus of many societal topics beyond medicine, including education, consumerism, and the justice system. In combination, advances made by basic, translational, and clinical neuroscience research in the next 50 years have great potential for lasting improvements in human health, the economy, and society.

Fall

Bianca Jones Marlin Books, Et Al.
(2019) Science

  • In his latest novel, Fall, Neal Stephenson tells the story of Richard Forthrast, better known as “Dodge,” a video game magnate who has willed his brain to research in the hopes of being reanimated. Heeding the call of the “Eutropians,” Dodge and seven others lead the charge for digital immortality, foretelling the emergence of new technology that will upload the brain of the financial elite to a virtual cloud. But what happens when a human-generated simulation begins to replicate the chaos by which life arose?

    With Joseph Jones Marlin

Sex-specific differences in oxytocin receptor expression and function for parental behavior

Mitre M., Kranz T.M., Marlin B.J., Schiavo J.K.., Erdjument-Bromage H., Zhang X., Minder J., Neubert T.A., Hackett T.A., Chao M.V., Froemke R.C.
(2017) Gender and the Genome

  • Parental care is among the most profound behavior expressed by humans and other animals. Despite intense interest in understanding the biological basis of parental behaviors, it remains unknown how much of parenting is encoded by the genome and which abilities instead are learned or can be refined by experience. One critical factor at the intersection between innate behaviors and experience-dependent learning is oxytocin, a neurohormone important for maternal physiology and neuroplasticity. Oxytocin acts throughout the body and brain to promote prosocial and maternal behaviors and modulates synaptic transmission to affect neural circuit dynamics. Recently we developed specific antibodies to mouse oxytocin receptors, found that oxytocin receptors are left lateralized in female auditory cortex, and examined how oxytocin enables maternal behavior by sensitizing the cortex to infant distress sounds. In this study we compare oxytocin receptor expression and function in male and female mice. Receptor expression is higher in adult female left auditory cortex than in right auditory cortex or males. Developmental profiles and mRNA expression were comparable between males and females. Behaviorally, male and female mice began expressing parental behavior similarly after cohousing with experienced females; however, oxytocin enhanced parental behavior onset in females but not males. This suggests that left lateralization of oxytocin receptor expression in females provides a mechanism for accelerating maternal behavior onset, although male mice can also effectively co-parent after experience with infants. The sex-specific pattern of oxytocin receptor expression might genetically predispose female cortex to respond to infant cues, which both males and females can also rapidly learn.

Oxytocin modulation of neural circuits for social behavior

Marlin B.J., Froemke R.C.
(2017) Developmental Neurobiology

  • Oxytocin is a hypothalamic neuropeptide that has gained attention for the effects on social behavior. Recent findings shed new light on the mechanisms of oxytocin in synaptic plasticity and adaptively modifying neural circuits for social interactions such as conspecific recognition, pair bonding, and maternal care. Here, we review several of these newer studies on oxytocin in the context of previous findings, with an emphasis on social behavior and circuit plasticity in various brain regions shown to be enriched for oxytocin receptors. We provide a framework that highlights current circuit-level mechanisms underlying the widespread action of oxytocin.

A distributed network for social cognition enriched for oxytocin receptors

Mitre M., Marlin B.J., Schiavo J., Morina E., Norden S., Hackett T.A., Aoki C., Chao M., Froemke R.C.
(2016) The Journal of Neuroscience

  • Oxytocin is a neuropeptide important for social behaviors such as maternal care and parent–infant bonding. It is believed that oxytocin receptor signaling in the brain is critical for these behaviors, but it is unknown precisely when and where oxytocin receptors are expressed or which neural circuits are directly sensitive to oxytocin. To overcome this challenge, we generated specific antibodies to the mouse oxytocin receptor and examined receptor expression throughout the brain. We identified a distributed network of female mouse brain regions for maternal behaviors that are especially enriched for oxytocin receptors, including the piriform cortex, the left auditory cortex, and CA2 of the hippocampus. Electron microscopic analysis of the cerebral cortex revealed that oxytocin receptors were mainly expressed at synapses, as well as on axons and glial processes. Functionally, oxytocin transiently reduced synaptic inhibition in multiple brain regions and enabled long-term synaptic plasticity in the auditory cortex. Thus modulation of inhibition may be a general mechanism by which oxytocin can act throughout the brain to regulate parental behaviors and social cognition.

Oxytocin enables maternal behaviour by balancing cortical inhibition

Marlin B.J., Mitre M., D’amour J.A., Chao M.V., Froemke R.C.
(2015) Nature

  • Oxytocin is important for social interactions and maternal behaviour. However, little is known about when, where and how oxytocin modulates neural circuits to improve social cognition. Here we show how oxytocin enables pup retrieval behaviour in female mice by enhancing auditory cortical pup call responses. Retrieval behaviour required the left but not right auditory cortex, was accelerated by oxytocin in the left auditory cortex, and oxytocin receptors were preferentially expressed in the left auditory cortex. Neural responses to pup calls were lateralized, with co-tuned and temporally precise excitatory and inhibitory responses in the left cortex of maternal but not pup-naive adults. Finally, pairing calls with oxytocin enhanced responses by balancing the magnitude and timing of inhibition with excitation. Our results describe fundamental synaptic mechanisms by which oxytocin increases the salience of acoustic social stimuli. Furthermore, oxytocin-induced plasticity provides a biological basis for lateralization of auditory cortical processing.

Development of auditory cortical synaptic receptive fields

Froemke R.C., Jones B.J.
(2011) Neuroscience and Biobehavioral Reviews

  • The central nervous system is plastic throughout life, but is most sensitive to the statistics of the sensory environment during critical periods of early postnatal development. In the auditory cortex, various forms of acoustic experience have been found to shape the formation of receptive fields and influence the overall rate of cortical organization. The synaptic mechanisms that control cortical receptive field plasticity are beginning to be described, particularly for frequency tuning in rodent primary auditory cortex. Inhibitory circuitry plays a major role in critical period regulation, and new evidence suggests that the formation of excitatory–inhibitory balance determines the duration of critical period plasticity for auditory cortical frequency tuning. Cortical inhibition is poorly tuned in the infant brain, but becomes co-tuned with excitation in an experience-dependent manner over the first postnatal month. We discuss evidence suggesting that this may be a general feature of the developing cortex, and describe the functional implications of such transient excitatory–inhibitory imbalance.