An Effective Model for Engaging Faculty and Undergraduate Students in Neuroscience Outreach with Middle Schoolers

Engaging undergraduate students in science outreach events is critical for improving future communication between scientists and community members. Outreach events are opportunities for faculty and undergraduates to utilize active learning strategies to engage non-scientists in scientific questions and principles. Through careful design of outreach events, undergraduate students can practice science communication skills while reaching populations of the public that remain underserved and underrepresented in scientific fields. Here we describe a classroom outreach event designed to give a broad overview of the field of neuroscience to middle school students of all backgrounds by delivering the content in school, during school hours. Through a variety of active learning strategies, middle school students learned about basic structures of the brain and their corresponding functions. Additionally, these students participated in demonstrations during which they generated and tested their own hypotheses and learned about sensory transmission and responses. We designed the lesson to meet the educational goals for middle school students, fulfilling the criteria for the Next Generation Science Standard MS-LS1-8 (NGSS Lead States, 2013). We evaluated the impact of the event on both undergraduate student instructors and middle school participants. Our results demonstrate that these outreach events effectively deliver new content to middle school students while also reinforcing the importance and value of outreach to undergraduate instructors

Oh, Behave! Behavior as an Interaction between Genes & the Environment

This lesson is designed to teach students that behavior is a trait shaped by both genes and the environment. Students will read a scientific paper, discuss and generate predictions based on the ideas and data therein, and model the relationships between genes, the environment, and behavior. The lesson is targeted to meet the educational goals of undergraduate introductory biology, evolution, and animal behavior courses, but it is also suitable for advanced high school biology students. This lesson meets the criteria for the Next Generation Science Standard HS-LS4, Biological Evolution: Unity and Diversity (NGSS Lead States, 2013)

Brainstem Cholinergic Modulation of Muscle Tone in Infant Rats

In week-old rats, lesions of the dorsolateral pontine tegmentum (DLPT) and nucleus pontis oralis (PnO) have opposing effects on nuchal muscle tone. Specifically, pups with DLPT lesions exhibit prolonged bouts of nuchal muscle atonia (indicative of sleep) and pups with PnO lesions exhibit prolonged bouts of high nuchal muscle tone (indicative of wakefulness). Here we test the hypothesis that nuchal muscle tone is modulated, at least in part, by cholinergically mediated interactions between these two regions. First, in unanesthetized pups, we found that chemical infusion of the cholinergic agonist carbachol (22 mM, 0.1 µL) within the DLPT produced high muscle tone. Next, chemical lesions of the nucleus pontis oralis (PnO) were used to produce a chronic state of high nuchal muscle tone, at which time the cholinergic antagonist scopolamine (10 mM, 0.1 µL) was infused into the DLPT. Scopolamine effectively decreased nuchal muscle tone, thus suggesting that lesions of the PnO increase muscle tone via cholinergic activation of the DLPT. Using 2-deoxyglucose (2-DG) autoradiography, metabolic activation throughout the DLPT was observed after PnO lesions. Finally, consistent with the hypothesis that PnO inactivation produces high muscle tone, infusion of the sodium channel blocker, lidocaine (2%), into the PnO of unanesthetized pups produced rapid increases in muscle tone. We conclude that, even early in infancy, the DLPT is critically involved in the regulation of muscle tone and behavioral state and that its activity is modulated by a cholinergic mechanism that is directly or indirectly controlled by the PnO

The Development of Sleep-Wake Rhythms and the Search for Elemental Circuits in the Infant Brain

Despite the predominance of sleep in early infancy, developmental science has yet to play a major role in shaping concepts and theories about sleep and its associated ultradian and circadian rhythms. Here we argue that developmental analyses help us to elucidate the relative contributions of the brainstem and forebrain to sleep-wake control and to dissect the neural components of sleep-wake rhythms. Developmental analysis also makes it clear that sleep-wake processes in infants are the foundation for those of adults. For example, the infant brainstem alone contains a fundamental sleep-wake circuit that is sufficient to produce transitions among wakefulness, quiet sleep, and active sleep. In addition, consistent with the requirements of a flip-flop model of sleep-wake processes, this brainstem circuit supports rapid transitions between states. Later in development, strengthening bidirectional interactions between the brainstem and forebrain contribute to the consolidation of sleep and wake bouts, the elaboration of sleep homeostatic processes, and the emergence of diurnal or nocturnal circadian rhythms. The developmental perspective promoted here critically constrains theories of sleep-wake control and provides a needed framework for the creation of fully realized computational models. Finally, with a better understanding of how this system is constructed developmentally, we will gain insight into the processes that govern its disintegration due to aging and disease

Lesions of the Intergeniculate Leaflet Lead to a Reorganization in Circadian Regulation and a Reversal in Masking Responses to Photic Stimuli in the Nile Grass Rat

Light influences the daily patterning of behavior by entraining circadian rhythms and through its acute effects on activity levels (masking). Mechanisms of entrainment are quite similar across species, but masking can be very different. Specifically, in diurnal species, light generally increases locomotor activity (positive masking), and in nocturnal ones, it generally suppresses it (negative masking). The intergeniculate leaflet (IGL), a subdivision of the lateral geniculate complex, receives direct retinal input and is reciprocally connected with the primary circadian clock, the suprachiasmatic nucleus (SCN). Here, we evaluated the influence of the IGL on masking and the circadian system in a diurnal rodent, the Nile grass rat (Arvicanthis niloticus), by determining the effects of bilateral IGL lesions on general activity under different lighting conditions. To examine masking responses, light or dark pulses were delivered in the dark or light phase, respectively. Light pulses at Zeitgeber time (ZT) 14 increased activity in control animals but decreased it in animals with IGL lesions. Dark pulses had no effect on controls, but significantly increased activity in lesioned animals at ZT0. Lesions also significantly increased activity, primarily during the dark phase of a 12:12 light/dark cycle, and during the subjective night when animals were kept in constant conditions. Taken together, our results suggest that the IGL plays a vital role in the maintenance of both the species-typical masking responses to light, and the circadian contribution to diurnality in grass rats

Melanopsin-Containing ipRGCs Are Resistant to Excitotoxic Injury and Maintain Functional Non-Image Forming Behaviors After Insult in a Diurnal Rodent Model

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are critical for the light signaling properties of non-image forming vision. Melanopsin-expressing ipRGCs project to retinorecipient brain regions involved in modulating circadian rhythms. Melanopsin has been shown to play an important role in how animals respond to light, including photoentrainment, masking (i.e., acute behavioral responses to light), and the pupillary light reflex (PLR). Importantly, ipRGCs are resistant to various forms of damage, including ocular hypertension, optic nerve crush, and excitotoxicity via N-methyl-D-aspartic acid (NMDA) administration. Although these cells are resistant to various forms of injury, the question still remains whether or not these cells remain functional following injury. Here we tested the hypothesis that ipRGCs would be resistant to excitotoxic damage in a diurnal rodent model, the Nile grass rat (Arvicanthis niloticus). In addition, we hypothesized that following insult, grass rats would maintain normal circadian entrainment and masking to light. In order to test these hypotheses, we injected NMDA intraocularly and examined its effect on the survivability of ipRGCs and RGCs, along with testing behavioral and functional consequences. Similar to findings in nocturnal rodents, ipRGCs were spared from significant damage but RGCs were not. Importantly, whereas image-forming vision was significantly impaired, non-image forming vision (i.e, photoentrainment, masking, and PLR) remained functional. The present study aims to characterize the resistance of ipRGCs to excitotoxicity in a diurnal rodent model

Intergeniculate Leaflet Lesions Result in Differential Activation of Brain Regions Following the Presentation of Photic Stimuli in Nile Grass Rats

The intergeniculate leaflet (IGL) plays an important role in the entrainment of circadian rhythms and the mediation of acute behavioral responses to light (i.e., masking). Recently, we reported that IGL lesions in diurnal grass rats result in a reversal in masking responses to light as compared to controls. Here, we used Fos as a marker of neural activation to examine the mechanisms by which the IGL may influence this masking effect of light in grass rats. Specifically, we examined the patterns of Fos activation in retinorecipient areas and in brain regions that receive IGL inputs following 1-h light pulses given during the early night in IGL-lesioned and sham-operated grass rats. Three patterns emerged: (1) IGL lesions had no effect on the Fos response to light, (2) IGL lesions resulted in a reversal in Fos responses to light, and (3) IGL lesions resulted in a lack of a Fos response to light. Of specific interest were the suprachiasmatic nucleus (SCN) and the olivary pretectal nucleus (OPT), both of which are retinorecipient and connect reciprocally with the IGL. Light-induced Fos expression in the SCN was unaffected by IGL lesions, whereas the OPT exhibited a significant reduction in Fos expression following a light pulse in animals with IGL lesions. Altogether, our results suggest that the OPT, but not the SCN, exhibits a reversal in Fos responses to light following IGL lesions that reverse masking responses in diurnal grass rats. Our results suggest that interconnections between the IGL and downstream brain areas (e.g., OPT) may play a role in determining the direction of the behavioral response to light

Day-night Differences in Neural Activation in Histaminergic and Serotonergic Areas with Putative Projections to the Cerebrospinal Fluid in a Diurnal Brain

In nocturnal rodents, brain areas that promote wakefulness have a circadian pattern of neural activation that mirrors the sleep/wake cycle, with more neural activation during the active phase than during the rest phase. To investigate whether differences in temporal patterns of neural activity in wake-promoting regions contribute to differences in daily patterns of wakefulness between nocturnal and diurnal species, we assessed Fos expression patterns in the tuberomammillary (TMM), supramammillary (SUM), and raphe nuclei of male grass rats maintained in a 12:12 h light-dark cycle. Day-night profiles of Fos expression were observed in the ventral and dorsal TMM, in the SUM, and in specific subpopulations of the raphe, including serotonergic cells, with higher Fos expression during the day than during the night. Next, to explore whether the cerebrospinal fluid is an avenue used by the TMM and raphe in the regulation of target areas, we injected the retrograde tracer cholera toxin subunit beta (CTB) into the ventricular system of male grass rats. While CTB labeling was scarce in the TMM and other hypothalamic areas including the suprachiasmatic nucleus, which contains the main circadian pacemaker, a dense cluster of CTB-positive neurons was evident in the caudal dorsal raphe, and the majority of these neurons appeared to be serotonergic. Since these findings are in agreement with reports for nocturnal rodents, our results suggest that the evolution of diurnality did not involve a change in the overall distribution of neuronal connections between systems that support wakefulness and their target areas, but produced a complete temporal reversal in the functioning of those systems

Distinct Retinohypothalamic Innervation Patterns Predict the Developmental Emergence of Species-typical Circadian Phase Preference in Nocturnal Norway Rats and Diurnal Nile Grass Rats

How does the brain develop differently to support nocturnality in some mammals, but diurnality in others? To answer this question, one might look to the suprachiasmatic nucleus (SCN), which is entrained by light via the retinohypothalamic tract (RHT). However, because the SCN is more active during the day in all mammals studied thus far, it alone cannot determine circadian phase preference. In adult Norway rats (Rattus norvegicus), which are nocturnal, the RHT also projects to the ventral subparaventricular zone (vSPVZ), an adjacent region that expresses an in-phase pattern of SCN-vSPVZ neuronal activity. In contrast, in adult Nile grass rats (Arvicanthis niloticus), which are diurnal, an anti-phase pattern of SCN-vSPVZ neuronal activity is expressed. We hypothesized that these species differences result in part from a weak or absent RHT-to-vSPVZ projection in grass rats. Here, using a developmental comparative approach, we assessed species differences in behavior, hypothalamic activity, and RHT anatomy. We report that a robust retina-to-vSPVZ projection develops in Norway rats around the end of the second postnatal week when nocturnal wakefulness and the in-phase pattern of neuronal activity emerge. In grass rats, however, such a projection does not develop and the emergence of the anti-phase pattern during the second postnatal week is accompanied by increased diurnal wakefulness. When considered within the context of previously published reports on RHT projections in a variety of species, the current findings suggest that how and when the retina connects to the hypothalamus differentially shapes brain and behavior to produce animals that occupy opposing temporal niches

The Distance to NGC 4993: The Host Galaxy of the Gravitational-wave Event GW170817

The historic detection of gravitational waves from a binary neutron star merger (GW170817) and its electromagnetic counterpart led to the first accurate (sub-arcsecond) localization of a gravitational-wave event. The transient was found to be $\sim$10" from the nucleus of the S0 galaxy NGC 4993. We report here the luminosity distance to this galaxy using two independent methods. (1) Based on our MUSE/VLT measurement of the heliocentric redshift ($z_{\rm helio}=0.009783\pm0.000023$) we infer the systemic recession velocity of the NGC 4993 group of galaxies in the cosmic microwave background (CMB) frame to be $v_{\rm CMB}=3231 \pm 53$ km s$^{-1}$. Using constrained cosmological simulations we estimate the line-of-sight peculiar velocity to be $v_{\rm pec}=307 \pm 230$ km s$^{-1}$, resulting in a cosmic velocity of $v_{\rm cosmic}=2924 \pm 236$ km s$^{-1}$ ($z_{\rm cosmic}=0.00980\pm 0.00079$) and a distance of $D_z=40.4\pm 3.4$ Mpc assuming a local Hubble constant of $H_0=73.24\pm 1.74$ km s$^{-1}$ Mpc$^{-1}$. (2) Using Hubble Space Telescope measurements of the effective radius (15.5" $\pm$ 1.5") and contained intensity and MUSE/VLT measurements of the velocity dispersion, we place NGC 4993 on the Fundamental Plane (FP) of E and S0 galaxies. Comparing to a frame of 10 clusters containing 226 galaxies, this yields a distance estimate of $D_{\rm FP}=44.0\pm 7.5$ Mpc. The combined redshift and FP distance is $D_{\rm NGC 4993}= 41.0\pm 3.1$ Mpc. This 'electromagnetic' distance estimate is consistent with the independent measurement of the distance to GW170817 as obtained from the gravitational-wave signal ($D_{\rm GW}= 43.8^{+2.9}_{-6.9}$ Mpc) and confirms that GW170817 occurred in NGC 4993.Comment: 9 pages, 5 figure