Enteric neuronal substrates underlying spontaneous and evoked neurogenic contractions in mouse colon.

Background And Aims: Gastrointestinal motility persists when peripheral cholinergic signaling is blocked genetically or pharmacologically, and a recent study suggests nitric oxide drives propagating neurogenic contractions.

Methods: To determine the neuronal substrates that underlie these contractions, we measured contractile-associated movements together with calcium responses of cholinergic or nitrergic myenteric neurons in un-paralyzed ex vivo preparations of whole mouse colon. We chose to look at these two subpopulations because they encompass nearly all myenteric neurons.

Age is associated with altered locomotor and hypothermic response to acute nicotine.

Cigarette smoking is at an all-time low. However, nicotine consumption has diversified with the introduction of commercial tobacco products that include Electronic Nicotine Delivery Systems. Nicotine is the main psychoactive component of tobacco and contributes to the addictive properties of tobacco products.

Alcohol and fear conditioning produce strain-specific changes in the dorsal hippocampal transcriptome of adolescent C57BL/6J and DBA/2J mice.

Background: Adolescent sensitivity to alcohol is influenced by genetic background. Data from our laboratory suggested that adolescent C57BL/6J and DBA/2J inbred mice differed in susceptibility to alcohol-induced deficits in dorsal hippocampus-dependent contextual fear learning.

Methods: To investigate the biological underpinnings of this strain difference, we examined dorsal hippocampus gene expression using RNA-sequencing after alcohol or saline administration followed by Pavlovian fear conditioning across male and female C57BL/6J and DBA/2J adolescents.

Modulation of intracellular calcium activity in interstitial cells of Cajal by inhibitory neural pathways within the internal anal sphincter.

The internal anal sphincter (IAS) functions to maintain continence. Previous studies utilizing mice with cell-specific expression of GCaMP6f revealed two distinct subtypes of intramuscular interstitial cells of Cajal (ICC-IM) with differing Ca activities in the IAS. The present study further examined Ca activity in ICC-IM and its modulation by inhibitory neurotransmission.

Perisynaptic Schwann Cells: Guardians of Neuromuscular Junction Integrity and Function in Health and Disease.

The neuromuscular junction (NMJ) is a highly reliable synapse to carry the control of the motor commands of the nervous system over the muscles. Its development, organization, and synaptic properties are highly structured and regulated to support such reliability and efficacy. Yet, the NMJ is also highly plastic, able to react to injury, and able to adapt to changes.

Transfer-bound community college students' biology identity and perception of teaching.

Community colleges are frequently an affordable, accessible entrance to a Science, Technology, Engineering, and Mathematics (STEM) education and career, but the transition from a 2-year program to a 4-year institution can be tumultuous. In this mixed-methods study, we explore the experiences of transfer and prospective transfer students. Through surveys and interviews, we identify the challenges faced by and the supports desired by biology transfer students.

Adolescent intermittent alcohol exposure produces strain-specific cross-sensitization to nicotine and other behavioral adaptations in adulthood in C57BL/6J and DBA/2J mice.

Adolescent alcohol exposure is associated with lasting behavioral changes in humans and in mice. Prior work from our laboratory and others have demonstrated that C57BL/6J and DBA/2J mice differ in sensitivity to some effects of acute alcohol exposure during adolescence and adulthood. However, it is unknown if these strains differ in cognitive, anxiety-related, and addiction-related long-term consequences of adolescent intermittent alcohol exposure.

Postsynaptic Calcium Extrusion at the Mouse Neuromuscular Junction Alkalinizes the Synaptic Cleft.

Neurotransmission is shaped by extracellular pH. Alkalization enhances pH-sensitive transmitter release and receptor activation, whereas acidification inhibits these processes and can activate acid-sensitive conductances in the synaptic cleft. Previous work has shown that the synaptic cleft can either acidify because of synaptic vesicular release and/or alkalize because of Ca extrusion by the plasma membrane ATPase (PMCA).

Epigenetic and long-term effects of nicotine on biology, behavior, and health.

Tobacco and nicotine use are associated with disease susceptibility and progression. Health challenges associated with nicotine and smoking include developmental delays, addiction, mental health and behavioral changes, lung disease, cardiovascular disease, endocrine disorders, diabetes, immune system changes, and cancer. Increasing evidence suggests that nicotine-associated epigenetic changes may mediate or moderate the development and progression of a myriad of negative health outcomes.

High signal-to-noise imaging of spontaneous and 5 ns electric pulse-evoked Ca2+ signals in GCaMP6f-expressing adrenal chromaffin cells isolated from transgenic mice.

In studies exploring the potential for nanosecond duration electric pulses to serve as a novel modality for neuromodulation, we found that a 5 ns pulse triggers an immediate rise in [Ca2+]i in isolated bovine adrenal chromaffin cells. To facilitate ongoing efforts to understand underlying mechanisms and to work toward carrying out investigations in cells in situ, we describe the suitability and advantages of using isolated murine adrenal chromaffin cells expressing, in a Cre-dependent manner, the genetically-encoded Ca2+indicator GCaMP6f. Initial experiments confirmed that Ca2+ responses evoked by a 5 ns pulse were similar between fluorescent Ca2+ indicator-loaded murine and bovine chromaffin cells, thereby establishing that 5 ns-elicited excitation of chromaffin cells occurs reproducibly across species.

Chronic nicotine exposure alters sperm small RNA content in C57BL/6J mouse model.

Multigenerational inheritance is a nongenomic form of heritability characterized by altered phenotypes in the first generation born from the exposed parent. Multigenerational factors may account for inconsistencies and gaps in heritable nicotine addiction vulnerability. Our lab previously found that F1 offspring of male C57BL/6J mice chronically exposed to nicotine exhibited altered hippocampus functioning and related learning, nicotine-seeking, nicotine metabolism, and basal stress hormones.

Interstrain differences in adolescent fear conditioning after acute alcohol exposure.

Adolescent sensitivity to alcohol is a predictor of continued alcohol use and misuse later in life. Thus, it is important to understand the many factors that can impact alcohol sensitivity. Data from our laboratory suggested that susceptibility to alcohol-associated contextual fear learning deficits varied among adolescent and adult mice from two mouse strains.

Kir4.1 is specifically expressed and active in non-myelinating Schwann cells.

Non-myelinating Schwann cells (NMSC) play important roles in peripheral nervous system formation and function. However, the molecular identity of these cells remains poorly defined. We provide evidence that Kir4.

Genetic differences in nicotine sensitivity and metabolism in C57BL/6J and NOD/ShiLtJ mouse strains.

Genetic background impacts sensitivity to nicotine's rewarding and aversive effects and metabolism, which influences susceptibility to nicotine addiction. This is important because sensitivity to nicotine influences susceptibility to nicotine addiction. Thus, understanding genetic contribution to nicotine sensitivity can aid in identifying risk factors for nicotine addiction.

The effect of acute nicotine administration on human delay cued and context fear conditioning.

Nicotine has been shown to facilitate hippocampal-dependent context fear conditioning (FC), but not hippocampal-independent delay cued fear conditioning. Studies examining the effects of nicotine on learned fear have been exclusively limited to nonhumans. The present study aimed to translate nonhuman findings by investigating the effects of nicotine on cued and context fear in humans using a virtual reality (VR) analog of the fear conditioning task.

Inbred mouse strain differences in alcohol and nicotine addiction-related phenotypes from adolescence to adulthood.

Understanding the genetic basis of a predisposition for nicotine and alcohol use across the lifespan is important for public health efforts because genetic contributions may change with age. However, parsing apart subtle genetic contributions to complex human behaviors is a challenge. Animal models provide the opportunity to study the effects of genetic background and age on drug-related phenotypes, while controlling important experimental variables such as amount and timing of drug exposure.

Genetic influences impacting nicotine use and abuse during adolescence: Insights from human and rodent studies.

Nicotine use continues to be a major public health concern, with an alarming recent rise in electronic cigarette consumption. Heritability estimates of nicotine use and abuse range from 40% to 80%, providing strong evidence that genetic factors impact nicotine addiction-relevant phenotypes. Although nicotine use during adolescence is a key factor in the development of addiction, it remains unclear how genetic factors impact adolescent nicotine use and abuse.

Propulsive colonic contractions are mediated by inhibition-driven poststimulus responses that originate in interstitial cells of Cajal.

The peristaltic reflex is a fundamental behavior of the gastrointestinal (GI) tract in which mucosal stimulation activates propulsive contractions. The reflex occurs by stimulation of intrinsic primary afferent neurons with cell bodies in the myenteric plexus and projections to the lamina propria, distribution of information by interneurons, and activation of muscle motor neurons. The current concept is that excitatory cholinergic motor neurons are activated proximal to and inhibitory neurons are activated distal to the stimulus site.

Ultrashort nanosecond electric pulses activate a conductance in bovine adrenal chromaffin cells that involves cation entry through TRPC and NALCN channels.

In whole-cell voltage clamped bovine adrenal chromaffin cells maintained at a holding potential of -70 mV, a single 5 ns, 5 MV/m pulse elicited an inward current carried mainly by Na that displayed inward rectification and a reversal potential near -3 mV, a voltage consistent with a non-selective cation current. The broad-spectrum inhibitors of transient receptor potential (TRP) channels, La (10 μM), Gd (10 μM), SKF-96365 (50 μM) and 2-aminoethoxydiphenyl borane (2-APB; 100 μM), inhibited the current similarly by ∼72%, ∼83%, ∼68% and ∼76%, respectively. Depleting membrane cholesterol with methyl-β-cyclodextrin (MβCD; 1-6 mg/ml) or inhibiting phosphatidylinositol 4,5-bisphosphate (PIP) synthesis with wortmannin (20 and 40 μM) produced a similar level of inhibition on the NEP-induced conductance as the broad spectrum TRP channel inhibitors.

Genetic Differences in Dorsal Hippocampus Acetylcholinesterase Activity Predict Contextual Fear Learning Across Inbred Mouse Strains.

Learning is a critical behavioral process that is influenced by many neurobiological systems. We and others have reported that acetylcholinergic signaling plays a vital role in learning capabilities, and it is especially important for contextual fear learning. Since cholinergic signaling is affected by genetic background, we examined the genetic relationship between activity levels of acetylcholinesterase (AChE), the primary enzyme involved in the acetylcholine metabolism, and learning using a panel of 20 inbred mouse strains.

Gene Cluster Variants Predict Liver Telomere Length in Mice.

Variants in a gene cluster upstream-adjacent to on human chromosome 3, which includes genes , , and , have been associated with telomere length in several human populations. Currently, the mechanism by which variants in the gene cluster influence telomere length in humans is unknown. Given the proximity between the gene cluster and (~0.

The impact of adolescent stress on nicotine use and affective disorders in rodent models.

Recent findings indicate that stress exposure during adolescence contributes to the development of both nicotine use and affective disorders, suggesting a potential shared biological pathway. One key system that may mediate the association between adolescent stress and nicotine or affective outcomes is the hypothalamic-pituitary-adrenal (HPA) axis. Here we reviewed evidence regarding the effects of adolescent stress on nicotine responses and affective phenotypes and the role of the HPA-axis in these relationships.

Therapeutic potential of ketamine for alcohol use disorder.

Excessive alcohol consumption is involved in 1/10 of deaths of U.S. working-age adults and costs the country around $250,000,000 yearly.