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Introduction
Publications
Publications (59)
Exposure to early life adversity (ELA), including childhood maltreatment, is one of the most significant risk factors for the emergence of neuropsychiatric disorders in adolescence and adulthood. Despite this relationship being well established, the underlying mechanisms remain unclear. One way to achieve this understanding is to identify molecular...
Appropriate expression of fear in the face of threats in the environment is essential for survival. The sustained expression of fear in the absence of threat signals is a central pathological feature of trauma- and anxiety-related disorders. Our understanding of the neural circuitry that controls fear inhibition coalesces around the amygdala, hippo...
Exposure to stress is a risk factor for perturbed mental health, including impoverished regulation of emotional and physiological responses that accompany anxiety and mood disorders, substance abuse and behavioral disorders. Such disruptions to well-being could be triggered by discrete environmental events or pervasive early life stress (ELS) resul...
Fear 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 in...
Dysfunctions in memory recall lead to pathological fear; a hallmark of trauma-related disorders, like posttraumatic stress disorder (PTSD). Both, heightened recall of an association between a cue and trauma, as well as impoverished recall that a previously trauma-related cue is no longer a threat, result in a debilitating fear toward the cue. Gluco...
Dysfunctions in memory recall lead to pathological fear; a hallmark of trauma-related disorders, like Post-Traumatic Stress Disorder (PTSD). Heightened recall of an association between a cue and trauma, as well as impoverished recall that a previously trauma-related cue is no longer a threat both result in a debilitating fear toward the cue. Glucoc...
Brain plasticity is dynamically regulated across the life span, peaking during windows of early life. Typically assessed in the physiological range of milliseconds (real time), these trajectories are also influenced on the longer timescales of developmental time (nurture) and evolutionary time (nature), which shape neural architectures that support...
Salient sensory environments experienced by a parental generation can exert intergenerational influences on offspring. While these data provide an exciting new perspective on biological inheritance, questions remain about causes and consequences of intergenerational influences of salient sensory experience. We previously showed that exposing male m...
Significance
The generalization of fear responses toward neutral stimuli is a highly prevalent and debilitating dimension of trauma- and anxiety-related disorders. Understanding the neural circuits that underlie the ability to suppress fear generalization is of significant translational interest. Recent studies have largely focused on examining fea...
Salient sensory environments experienced by a parental generation can exert intergenerational influences on offspring, including offspring not conceived at the time of the parental experience. While these data provide an exciting new perspective on biological inheritance, questions remain about causes and consequences of intergenerational influence...
Fear expressed towards threat-associated stimuli is an adaptive behavioral response. In contrast, the generalization of fear responses toward non-threatening cues is maladaptive and a debilitating dimension of trauma- and anxiety-related disorders. Expressing fear to appropriate stimuli and suppressing fear generalization requires integration of re...
Background:
Stressors affect populations exposed to them as well as offspring. Strategies preventing the intergenerational propagation of effects of stress would benefit public health. Olfactory cue-based fear conditioning provides a framework to address this issue.
Methods:
We 1) exposed adult male mice to an odor, acetophenone (Ace) or Lyral (...
Women are at increased risk of developing post-traumatic stress disorder (PTSD) following a traumatic event. Recent studies suggest that this may be mediated, in part, by circulating estrogen levels. This study evaluated the hypothesis that individual variation in response to estrogen levels contributes to fear regulation and PTSD risk in women. We...
Posttraumatic stress disorder (PTSD) affects 5–10% percent of the US adult population with a higher prevalence among women compared with men. Although it remains unclear how biological sex associates with susceptibility to PTSD, one mechanism may involve a role for estrogen in a gene by environment interaction. We previously demonstrated a sex-depe...
Significance
For individuals to develop sexually dimorphic body parts and behavior, their cells must know their sex. In the fruit fly Drosophila melanogaster , this process is carried out by a series of genes ending with fruitless ( fru ) and doublesex ( dsx ). We found that both Fru and Dsx regulate the expression of the leucine-rich repeat G prot...
Significance
Olfactory cues may be paired with traumatic experiences in humans (e.g., the smell of a physical abuser), and subsequent exposure to the environmental odor cue may serve as a reminder of the traumatic event and trigger posttraumatic stress disorder symptoms. Very few studies have investigated the mechanisms accompanying the processing...
Trajectories toward risk or resilience in psychiatric disorders are influenced by acquired and inherited factors. More recently, evidence from rodent studies suggest that acquired risk factors can be transmitted through non-genomic, epigenetic mechanisms to subsequent generations, potentially contributing to a cycle of disease and disease risk. Her...
Gene expression and regulation is an important sculptor of the behavior of organisms. Epigenetic mechanisms regulate gene expression not by altering the genetic alphabet but rather by the addition of chemical modifications to proteins associated with the alphabet or of methyl marks to the alphabet itself. Being dynamic, epigenetic mechanisms of gen...
Environmental factors routinely influence an organism's biology. The inheritance or transmission of such influences to descendant generations would be an efficient mode of information transfer across generations. The developmental stage at which a specific environment is encountered by the ancestral generation, and the number of generations over wh...
WE thank Gregory Francis for his careful reading of our article and associated commentary. We too remain amazed at this phenomenon, and we agree that much remains to be done to understand the underlying mechanisms. However, we have now replicated these effects multiple times within our laboratory
Unlabelled:
Using an array-based approach after auditory fear conditioning and microRNA (miRNA) sponge-mediated inhibition, we identified a role for miR-34a within the basolateral amygdala (BLA) in fear memory consolidation. Luciferase assays and bioinformatics suggested the Notch pathway as a target of miR-34a. mRNA and protein levels of Notch re...
The centromedial amygdala (CeM), a subdivision of the central amygdala (CeA), is believed to be the main output station of the amygdala for fear expression. We provide evidence that the Tac2 gene, expressed by neurons specifically within the CeM, is required for modulating fear memories. Tac2 is colocalized with GAD65 and CaMKIIα but not with PKCd...
Using olfactory molecular specificity, we examined the inheritance of parental traumatic exposure, a phenomenon that has been frequently observed, but not understood. We subjected F0 mice to odor fear conditioning before conception and found that subsequently conceived F1 and F2 generations had an increased behavioral sensitivity to the F0-conditio...
Brain-derived neurotrophic factor (BDNF) is critically involved in synaptic plasticity and neurotransmission. Our lab has previously found that BDNF activation of neurotrophic tyrosine kinase, receptor, type 2 (TrkB) is required for fear memory formation and that GABAA receptor (GABAAR) subunits and the GABAA clustering protein gephyrin are dynamic...
Most birds are socially monogamous, yet little is known about the neural pathways underlying avian monogamy. Recent studies have implicated dopamine as playing a role in courtship and affiliation in a socially monogamous songbird, the zebra finch (Taeniopygia guttata). In the present study, we sought to understand the specific contribution to pair...
Neuropsychopharmacology, the official publication of the American College of Neuropsychopharmacology, publishing the highest quality original research and advancing our understanding of the brain and behavior.
Exposure to stress and hallucinogens in adulthood evokes persistent alterations in neurocircuitry and emotional behaviour. The structural and functional changes induced by stress and hallucinogen exposure are thought to involve transcriptional alterations in specific effector immediate early genes. The immediate early gene, activity regulated cytos...
Both mammals and birds evolved from reptilian ancestors and, as such, this diverse group is pivotal to our understanding of the evolution of behavioral controlling mechanisms. In some reptiles sex is determined by heritable sex chromosomes, with species having male heterogamety (XX:XY) like mammals) while others exhibit female heterogamety (ZZ:ZW)...
Monoamines are implicated in the modulation of adult hippocampal neurogenesis in depression models and following chronic antidepressant treatment. Given the key role of Sonic hedgehog (Shh) in adult neurogenesis, we examined whether monoaminergic perturbations regulate the expression of Shh or its co-receptors Smoothened (Smo) and Patched (Ptc). Co...
The steroidogenic enzyme CYP17 is responsible for catalyzing the production of androgenic precursors, while CYP19 converts testosterone to estradiol. De novo neurosteroidogenesis in specific brain regions influences steroid hormone dependent behaviors. In the all-female lizard species Cnemidophorus uniparens, individuals alternately display both ma...
nd edition, published by Elsevier, and the attached copy is provided by Elsevier for the author's benefit and for the benefit of the author's institution, for non-commercial research and educational use including without limitation use in instruction at your institution, sending it to specific colleagues who you know, and providing a copy to your i...
Antidepressants induce structural remodeling in the adult hippocampus, including changes in dendritic arbors, axonal sprouting, neurogenesis, and endothelial cell proliferation. Such forms of structural plasticity take place in the context of the extracellular matrix environment and are known to be regulated by matrix metalloproteinases (MMPs), in...
Neuroendocrine mechanisms underlying complementary behaviors like male-typical mounting and female-typical receptivity are most often studied independently in males and females, respectively. Cnemidophorus uniparens is a unisexual lizard species consisting only of females that alternately express male- and female-like pseudosexual behavior across t...
Stress regulation of brain-derived neurotrophic factor (BDNF) is implicated in the hippocampal damage observed in depression. BDNF has a complex gene structure with four 5' untranslated exons (I-IV) with unique promoters, and a common 3' coding exon (V). To better understand the stress regulation of BDNF, we addressed whether distinct stressors dif...
Male leopard geckos that hatch from eggs incubated at a female-biased temperature (Tf) behave differently when compared with males hatching at a temperature which produces a male-biased sex ratio (Tm). We investigated the effect of incubation temperature and androgen implantation on aspects of the dopaminergic system of Tf and Tm males. Our data su...
Hormone-neurotransmitter interactions form an important link through which hormones influence a variety of behavioral processes. Typically, sexual behavior is dimorphic with males mounting receptive females. In the all-female lizard species Cnemidophorus uniparens, individuals display both male-like pseudocopulation and female-like receptivity. The...
Electroconvulsive seizure (ECS) induces structural remodelling in the adult mammalian brain, including an increase in adult hippocampal neurogenesis. The molecular mechanisms that underlie this increase in the proliferation of adult hippocampal progenitors are at present not well understood. We hypothesized that ECS may recruit the Sonic hedgehog (...
Brain-derived neurotrophic factor (BDNF) is expressed at high levels in the hippocampus, where it has been implicated in physiological functions such as the modulation of synaptic strength as well as in the pathophysiology of epileptic seizures. BDNF expression is highly regulated and the BDNF gene can generate multiple transcript isoforms by alter...
Antidepressants are known to increase brain derived neurotrophic factor (BDNF) mRNA in the adult rat brain. The BDNF gene has four differentially regulated promoters that generate four transcript forms, each containing a unique non-coding 5' exon (exon I-IV) and a common 3' coding exon. Using in situ hybridization with exon-specific riboprobes, we...
Questions
Questions (4)
I am looking for advice on how to extract RNA from mouse sperm (including ncRNA). I have used the Qiagen miRNeasy kit but am getting a lot of 230nm absorbance (RWT wash skipped because this step gave me high 230nm when used on brain tissue). Thank you.
I am trying to conduct X-ChIP on mouse brain punches and am having trouble getting my sonication parameters right. Using a Bioruptor machine on High setting 30s On 30s Off for 30 cycles yields smears in the 1500-800 range. Does anyone know of specific and detailed protocols for X-ChIP on mouse brain punches and sonication parameters to get chromatin in the 200-800bp range?
I’ve done a ChIP twice now (independent samples), and while I get amplification for genes using my immunoprecipitated samples as template, I get no amplification using Input DNA as my template. Any ideas? I just repeated the qPCR and got amplification in 2 out of 6 input DNA template rxns (without having done anything different than my previous qPCR). The no amplification and now 2/6 being amplified is baffling.
I am looking for a detailed protocol to conduct N-ChIP on mouse sperm (right from collection and then processing). Any ideas? (Preferably not the bare-bones protocols that are published in some recent publications). For now, I seem to be losing sample before the lysis step, then when I try and visualize the nuclei after lysis using Trypan Blue (probably not the best stain), I have no idea what i should expect to see. I definitely do not see bodies like the nuclei i see when i work on other samples (eg. brain). Also, at this point any protocols that will let me ChIP sperm samples will do.
Thank you.
