Lactate plays an important role in brain energy metabolism. It contributes to normal brain development and to neuroprotection in diabetic hypoglycemia, but its role in neonatal hypoglycemia is unclear. Moreover, lactate can work as a signaling substance via the lactate receptor HCAR1 (Hydroxycarboxylic acid receptor 1). Recent studies indicate that HCAR1 is protective in mouse models of neonatal hypoxic ischemia and has a role in metabolic regulation in glial cells during hypoglycemia. Here we have studied potential impacts of HCAR1 on axonal and myelin development in the cerebral cortex and corpus callosum of young (P21) wild-type (WT) mice and HCAR1 KO mice and in cortical organotypic brain slice cultures. The HCAR1 KO mice showed lower axonal area relative to WT in both cortex and corpus callosum. However, the myelin area was unaffected by HCAR1 KO. Using particle and colocalization analysis, we show that HCAR1 KO predominantly reduces axonal size in unmyelinated axons. Using an organotypic brain slice ...

The consequences of aging can vary dramatically between different brain regions and cell types. In the ventral midbrain, dopaminergic neurons develop physiological deficits with normal aging that likely convey susceptibility to neurodegeneration. While nearby GABAergic neurons are thought to be more resilient, decreased GABA signaling in other areas nonetheless correlates with age-related cognitive decline and the development of degenerative diseases. Here, we used two novel cell type-specific translating ribosome affinity purification models to elucidate the impact of healthy brain aging on the molecular profiles of dopamine and GABA neurons in the ventral midbrain. By analyzing differential gene expression from young adult (7-10 months) and old (21-24 months) mice, we detected commonalities in the aging process in both neuronal types, including increased inflammatory responses and upregulation of pro-survival pathways. Both cell types also showed downregulation of genes involved in synaptic connectivity ...

Distinct frontal regions make dissociable contributions to rule-guided decision-making, including the ability to learn and exploit associations between abstract rules and reward value, maintain those rules in memory, and evaluate choice outcomes. Value-based learning can be quantified using reinforcement learning (RL) models predicting optimal trial-wise choices and estimating learning rates, which can then be related to the intact functioning of specific brain areas by combining a modeling approach with lesion-behavioral data. We applied a three-parameter feedback-dependent RL model to behavioral data obtained from macaques with circumscribed lesions to the principal sulcus (PS), anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), superior dorsolateral prefrontal cortex (sdlPFC), and frontopolar cortex (FPC) performing a Wisconsin card sorting task (WCST) analog. Our modeling-based approach identified distinct lesion effects on component cognitive mechanisms contributing to WCST performance. OFC ...

The most important skill a scientist needs, after the skills needed to execute a study, is the ability to report his or her scientific endeavors in writing. The editors-in-chief of four international neuroscience journals — Brain and Behavior, the European Journal of Neuroscience, the Journal of Neuroscience Research, and Neuroscience, the journal of the International Brain Research Organization — come together in this workshop to offer insight into what editors look for, what their roles are, and what you can to do to make your paper stand out. Watch the recording to learn more about the review process, including why peer review is important, what’s essential to include in your paper, and how to be ethical and ensure reproducibility in your experiments.

Learn how to make yourself a stronger job candidate, consider career paths you may not have thought of, connect with like-minded scientists, and find work-life balance. In this interview, Samantha Baglot, a PhD student at the University of Calgary, in Canada, shares how she’s pursuing her passion for improving education through neuroscience outreach and project management. What made you want to start doing outreach, and how did you get involved? When I started my master's degree about three years ago, I joined the Neuroscience Graduate Student Association at The University of British Columbia. I was interested in what their vice president of outreach was doing. At the time, she was organizing Vancouver's Brain Bee and Brain Awareness Week events, as well as collaborative events with artists and other communities on campus. I worked with her. Then an opportunity came up for a project where we look at the history of neuroscience through cartoons, and I took the lead on that. I do a lot of delegating, organizing, and recruiting volunteers.

Developing strategic research and personal connections — a global network — can help you navigate career transitions and challenges and be successful in your career. In this workshop from Neuroscience 2018, a panel of researchers with experience living and working away from their home countries offered advice for building these culturally based support systems, centered around the four themes below. Read on for highlights and advice, and watch the recording to listen in on this interactive panel discussion.

Live imaging of neuronal populations often reveals a background signal that engulfs the signal from individual neurons. Typically, this background signal is dismissed as uninformative or as an epiphenomenon. We imaged in freely moving mice acetylcholine-releasing (cholinergic) interneurons in the striatum that play a critical role in basal ganglia function and dysfunction in movement disorders. Importantly, these interneurons give rise to a profusely dense neuropil of fine neuronal processes that fill the striatum. Under these circumstances, our analysis revealed the background signal arising from the neuropil represents a “mean-field” readout of the collective recurrent activity of cholinergic interneurons. Thus, the neuropil signal functions as a physiological readout of the network state. For over half a century, clinicians and scientists have known a disruption of the so-called balance between acetylcholine and dopamine released in the region of the brain called the striatum is a central pathological correlate of various movement disorders such as Parkinson’s disease and Huntington’s disease. This imbalance was deduced from biochemical and histological studies of the striatum. However, evidence for such an imbalance in the physiological activity of brain circuits has been lacking.

In the mouse, no complete innate behavioral circuit has been defined, and mechanistic understanding of the neurons that drive behavior remains largely unknown. Lisa Stowers was one of the first postdocs to work with Howard Hughes Medical Institute investigator Catherine Dulac on decoding the mouse olfactory system. In this Meet-the-Expert, she delves into why, 20 years after they began, there’s work left to do, and why innate behavior is not so easy to study as advertised. By watching you’ll gain an understanding of the means and metrics of analysis, assumptions of circuit coding, and interpretations of the effects of viral and optogenetic manipulations, contributing to a greater overall understanding of the coding of innate behavior.

Arianna Maffei is an associate professor at Stony Brook University, where she has led an independent research program since 2008. In this interview, she answers some of postdocs’ most common questions at the start of their careers, on topics including finding mentors, applying and interviewing for jobs, and starting a lab.

Open communication can help scientists and institutions increase public support for animal research by improving public trust, understanding of the necessity of animal research, and perception of how animal studies are conducted. In this recording of the Animals in Research Panel from Neuroscience 2018, learn effective ways to communicate openly and start positive conversations about animal research. Panelists will share strategies all scientists can use to increase public support in their local communities.