Abstracts

Keynote Speakers

Florian Engert

Department of Molecular & Cellular Biology, Harvard University
Fish feelings: Motivational internal states in larval zebrafish
Motivational states in larval zebrafish can regulate specific switching between behavioral priorities. I will explain how the oxytocin system regulates and relays processing of aversive and noxious stimuli, and how this can be extended to states of social isolation. Also, I will share our results on the role of hypothalamic serotonergic neurons in the regulation of hunger and its influence on switching between exploit vs explore strategies

Elizabeth Phelps

Department of Psychology, Harvard University
The Human Amygdala, Threat, and Anxiety: Translational Progress and Challenges
Animal models of associative threat learning provide a basis for understanding human fears and anxiety. This talk explores the successes and failures in translating the neural mechanisms of threat processing identified in animal models to complex human learning and the treatment of anxiety-related disorders.  First, I will briefly review how extinction and emotion regulation, techniques adapted in cognitive behavioral therapy treatments, can be used to control learned defensive responses via inhibitory signals from the ventromedial prefrontal cortex to the amygdala. One drawback of these techniques is threat responses are often weakly inhibited and can return, which has been proposed to underlie the significant relapse rate following cognitive behavioral therapies. I will then describe novel behavioral interventions that might result in a more lasting fear or threat reduction and will discuss efforts to incorporate these novel techniques to innovative treatments for anxiety-related disorders. Finally, I will reflect on how we might improve efforts to translate insights from the neurobiology of threat learning to the treatment of anxiety-related disorders.

Local Speakers

Karine Fenelon

Using the acoustic startle reflex as a readout of sensory information filtering

PrePulse Inhibition (PPI) of the acoustic startle reflex is the gold standard operational measure of sensorimotor gating, used in humans and translational models. PPI is impaired in various neurological and neuropsychiatric disorders where it is often predictive of psychosis, obsessions, compulsions, and sensorimotor or speech dysfunctions. The reversal of PPI deficits is routinely tested in disease experimental systems as pre-clinical trials of neurological drug screening. Yet, the cellular and circuit-level mechanisms remain largely unclear, even under non-pathological conditions, limiting therapeutic advances. Recent evidence ruled out the longstanding hypothesis that PPI is mediated by midbrain cholinergic inputs to the caudal pontine reticular nucleus (PnC). Instead, glutamatergic, glycinergic, and GABAergic inhibitory mechanisms are now suggested to be crucial for PPI, at the PnC level. Since dysfunctions of the midbrain and the amygdala are common to pathologies displaying sensorimotor gating deficits, we tested how direct projections originating from these regions to the PnC, contribute to PPI. Using mice, we employed tract-tracing, immunohistochemical analyses and in vitro electrophysiological recordings to demonstrate how glutamatergic and GABAergic inputs to PnC neurons modulate the PnC startle circuit. Then we used an in vivo Ca2+- dependent photo-sensitive approach to identify and manipulate neurons active during acoustic stimulations and PPI, with high spatio-temporal precision. Such knowledge allowed us to restore PPI in a schizophrenia-relevant mouse model, by photo-manipulating a specific subset of neurons. Our results show how brainstem mechanisms within the auditory startle circuit contribute to PPI. We therefore provide new insights to the clinically-relevant theoretical construct of PPI, which is disrupted in various psychiatric and neurological diseases.

Joseph Bergan

Psychological & Brain Sciences, UMass
Integrative circuits for social behavior in the medial amygdala
Social behaviors are essential for survival and rely on rapid integration, processing, and communication amongst brain-wide networks. The medial amygdala plays a key role in social behavior, acting as a hub for both receiving social information and initiating social interactions. Considerable work suggests that different cell types in the medial amygdala may be dedicated for specific behavioral responses including aggression, mating, and social recognition. In contrast, anatomical work from our lab highlights an unexpected level of integration between sensory and interoceptive factors in the medial amygdala. Broad integration is also clear in the moment-to-moment activity of medial amygdala neurons during social interactions. We believe that flexibility and the interwoven nature of neural pathways in the medial amygdala represent a design feature for social behaviors such as affiliation, parenting, social memory, predator avoidance, and aggression.

Meghan Huber

Mechanical and Industrial Engineering, UMass
Using Robots to Improve How We Move
Mobility serves as a cornerstone of independence, health, and overall well-being. Robots offer promise in enhancing mobility, be it through exoskeletons or gait retraining systems. However, to optimize their effectiveness, we must understand how humans adapt and learn to walk with these devices. In this talk, I will delve into our ongoing research efforts aimed at understanding and enhancing the synergy between human neuromotor system and robots to improve human mobility. Additionally, we explore novel robotic advancements designed to shift gait retraining from clinical settings into the everyday lives of patient.

Bruno Castro da Silva

The Role of Reward Systems in Artificial Intelligence: Challenges and Risks
Reinforcement learning is a branch of artificial intelligence focused on learning how to make decisions to solve problems. These algorithms have been successfully deployed in various real-life applications, including controlling stratospheric balloons, executing robotic locomotion tasks, optimizing medical treatments, performing package deliveries by drones, and constructing large language models like ChatGPT. RL and neuroscience share a remarkable point of contact: both dopamine and its computational equivalent are known to encode prediction error signals between old and new estimates of expected future rewards, playing a pivotal role in driving learning processes. In this talk, I will discuss the role of reward functions in AI, emphasizing the difficulties in designing artificial reward functions that ensure proper learning, providing evidence that direct maximization of rewards does not always lead to efficient learning, and discussing practical examples where reward functions often cause artificial agents to learn unsafe, unexpected, or undesirable behaviors.

Posters Abstracts

1, Deletion of Cryptochrome 1 Speeds Entrainment of the Liver Transcriptome: Evidence from Duper Hamsters

Bittman, E; Lee, YY; Hogenesch, JB

Biology UMass

The adverse health consequences of jet lag are proposed to result from protracted misalignment of metabolic and physiological function upon shifts to the entraining cycle. duper hamsters, which do not express Cry 1, experience a profound reduction in jet lag: they re-entrain locomotor activity 4-fold faster than wild type animals. Consistent with the misalignment hypothesis, the acceleration of cardiomyopathy and changes in adult neurogenesis that occur in wild type hamsters upon repeated 8h phase shifts are reduced in duper mutants. We lack evidence of the effect of Cry1 deficiency on phase shifts of either core clock components or transcripts that control critical metabolic and physiological functions. To address this gap, we compared wild type animals with duper mutant hamsters that either remained on a stable 14L:10D cycle or were subjected to an 8h phase advance. Groups of hamsters were killed at 2h intervals on the third circadian cycle after the shift. The liver transcriptome was assessed by RNA-Seq.

We found that Cry2 and ROR-c mRNAs were tonically elevated in duper mutant animals. In the absence of phase shifts, the expression of core clock genes including Bmal1, Per1-3, Rev-erb a, and Dbp peaked earlier in duper than in wild type mice. This is consistent with the short circadian period and the positive phase angle of entrainment of locomotor activity in the duper mutant. Most striking, expression of these core clock genes as well as important clock controlled genes such as Tef, Hif1a, and Alas1 completely shifted within 3 days of the 8h phase advance in the duper mutant. These transcripts only advanced a few hours in the wild type hamsters. These results validate use of locomotor activity as a set of “hands of the clock” and support the hypothesis that destabilization of the core clock mechanism by elimination of Cry1 reduces adverse effects of jet lag by accelerating re-alignment after phase shifts. Supported by NIH RO1-138551.

2, Does Extra Practice Promote Sleep-Dependent Memory Consolidation in Older Adults?

McSpirit-Brush, K; Woodward, O; Delvey, C; Spencer, RMC

NSB/PBS, UMass Amherst

Introduction: While sleep can improve memory performance, not all memory domains demonstrate this effect. Prior studies show that hippocampal engagement during encoding is necessary for subsequent sleep-dependent memory consolidation. However, motor sequence learning typically engages other areas and inconsistently demonstrates sleep-related gains, particularly among older adults. Hippocampal engagement via explicit sequence awareness and strong learning ability increases the possibility of sleep-related procedural memory gains. Therefore, we compared sleep-dependent memory consolidation on an explicit motor sequence task in older adults who received standard training to those who received additional training.

Methods: Healthy older adults (N=29; 67.7 ± 4.5 years; 72% female), assigned to a standard training group (n=15) or an over-training group (n=14), were trained on an explicit motor sequence learning task; standard training comprised 5 blocks of practice while over-training included 10. Performance was tested before (“immediate”) and after (“delayed”) a day spent awake and a night spent asleep (conditions separated by ~1 week, order counterbalanced). Skill learning was calculated by subtracting median reaction time during learned sequences from that of randomly-cued button presses. Change in skill learning from immediate to delayed test for the wake interval was contrasted with change across sleep, resulting in a sleep benefit score. Polysomnography was recorded during the overnight sleep visit.

Results: A planned comparison of immediate test results, to check baseline differences resulting from training, showed that the over-training group was significantly faster than the standard training group (t(2.059)=-4.217, p<.01). Analysis of sleep benefit scores showed no significant benefit with standard training (vs 0; p>.43), but a marginal benefit with over-training (t(13)=2.71, p=.055). However, over-training does not provide a significantly greater sleep benefit than standard training (t(28)=2.048, p=.222).

Conclusion: Our results show that additional training may improve the chances of demonstrating sleep-dependent memory gains on a motor sequence task in older adults. Moreover, we replicate prior findings that standard training does not demonstrate such gains. Because sleep stages N2 and N3 have been previously linked to improved memory across sleep, follow-up analysis will include polysomnography recordings.

Support: NIH R01 HL111695

3, R03: Early Alzheimers Forecasting in the Wild

Sidong Zhang, Ina Fiterau, Joyita Dutta

Computer Science

Alzheimer’s disease (AD) is the most common form of dementia, causing progressive cognitive impairment, disorientation, and memory loss. Despite years of clinical trials, there is currently no cure for AD and, by the time of diagnosis, as much as 60% of brain matter is already lost. Thus, forecasting Alzheimer's disease years ahead of onset is critical for attempts at early treatment, the selection of subjects for clinical trials, and to facilitate neurologists’ study of the disease.

Past research on machine learning for Alzheimer’s disease prediction was limited to using cognitive test scores and highly engineered volumetric features, while failing to leverage the potential information found in brain MRIs. Attempts to train 3D and 2D CNNs on the MRIs have been unsuccessful thus far, due to the insufficient amount of data samples available for the massive number of parameters that need to be learned. Moreover, forecasting AD using standard statistical models, simple MLPs and sequential models is typically limited to 6-12 months windows, model stability and performance dropping significantly for longer time windows.

To introduce more complex longitudinal data and detect future disease stages, we propose a sequential deep learning approach that is expressive enough to handle multimodal longitudinal data, with an added unsupervised mutual information CNN encoder to process the 3D MRI scans, while still maintaining stable forecasting performance over forecasting windows of two years or more. We integrate certain domain knowledge via selective features of the disease-relative areas’ volumetric data, cognitive test scores and demographic information. The model is designed to get latent features from the multimodal data during the training process that are informative to the forecasting task. To achieve this, we propose a hybrid model of RNN and CNN. On the RNN side, we study a RNN-like structure introducing latent anticipated features to enhance the forecasting performance. On the CNN side, we train a mutual information based unsupervised encoder and extract latent features from the 3D MRIs as supportive side information. The model we are developing will be capable of performing forecasting tasks 2-year ahead of time, while the instability issue brought by long-term forecasting is addressed by our new mechanism of training different parts of the model separately in different stages. One of the future directions of the project lies in forecasting the disease on a longer time gap without loss of accuracy and robustness.

While models trained and evaluated on ADNI data go some way to address the need to predict the incidence of AD years ahead of symptomatic onset, there are still several impediments in the application of the models toward the study of preemptive or palliative treatments. First, the specialized features in ADNI might not match what might be encountered in the real world. Cognitive tests might be different that the ones performed as part of ADNI, while the features engineered from brain MRIs in ADNI may not be practically obtainable for hospital-collected MRIs, placing barriers in the deployment of the models. Second, the distribution from the perspective of health status is different in the general population than in carefully controlled studies with AD-specific cohorts. Further, real-world data is more likely to be cross-sectional as opposed to longitudinal, with the predictive problem closer to survival analysis than a classification problem as it is often set up in studies using ADNI. Finally, the modalities exhibit various levels of predictive capacity over different time windows. We present techniques that address these challenges to make models trained on ADNI applicable to cross-sectional data from the UK biobank, as a proxy for data collected ‘in the wild’. We aim to understand the model performance and limitations, and the relative merits of the different modalities, in forecasting long term outcomes of ADRD.

4, A history of adolescent drinking increases myelination of axons within the corticotropin releasing factor-enriched subregion of the central amygdala in adult mice.

Flores-Bonilla A, Akli S, Senthikumar R, De Oliveira B, Rajvanshi A, Amira N, Richardson HN

Neuroscience and Behavior Program, University of Massachusetts Amherst

In the United States, approximately 11.1 million 12–25-year-olds reported binge drinking in 2022. Adolescent brains undergo substantial changes in neurocircuitry as oligodendrocytes (OLs) rapidly myelinate active axons which facilitates faster propagation of action potentials. The central amygdala (CeA) is enriched with cells expressing the stress response modulator corticotropin-releasing factor (CRF) peptide. Alcohol increases CeA cell activity and inhibiting CRF signaling in the CeA decreases alcohol consumption. Escalation in alcohol drinking has also been linked to genes involved in OL differentiation and myelin. A goal of this study is to understand how CRF and OLs may interact to affect alcohol drinking. We hypothesize that adolescent alcohol impacts the myelination of axons coming into and leaving the CeA. We used NG2-CreERTM; Tau-mGFP male and female transgenic mice to tag differentiating OLs with membrane-bound green fluorescent protein (GFP) and track the formation of new (de novo) myelin sheaths during adolescence. Following tamoxifen-induced Cre-recombination on postnatal days (P) 21-24, mice had access to water (n=5/sex) or alcohol (unsweetened 20%v/v) (n=4-5/sex) using a drinking-in-the-dark voluntary binge drinking model throughout early adolescence (P28-42). Drinking significantly escalated in the two weeks of access (t-test, p<0.05), with an average alcohol consumption of 3.3 ± 0.4 g/kg/4h in the first week and 4.6 ± 0.3 g/kg/4h in the second week. Mice were perfused and brains were collected after two months of abstinence. Brains were processed for immunohistochemical co-labeling of GFP and CRF proteins and counterstained with the fluorescent nuclear marker Hoechst. Confocal images were acquired using the CREST-V2 at 60X oil magnification with z-stacks of the CeA. CRF peptide expression was found higher in the CeA of females compared to males (main effect of sex, p<0.05). We also found evidence for de novo myelin sheaths (GFP+ fibers) in the CeA during adolescence and early adulthood in all groups. De novo myelination was higher in the alcohol group compared to water group only in males (treatment x sex interaction and Bonferroni post-hoc analysis, ps<0.05). These findings suggest alcohol impacts stress circuitry by increasing de novo myelination of axons interacting with CRF cells in the CeA. 

5, Nanoparticle mediated brain mapping for precision gene therapy

Jingjing Gao 

BME, Umass

Most disease-modifying treatments (DMTs) for central nervous system (CNS) diseases failed to make it to the market due to poor penetration across blood-brain barrier (BBB) and non-specific drug distribution induced side effects. We aim to establish the structure-property relationship of nanoparticles in terms of neural cell interactions and spatial distribution in the diseased brain, providing a toolbox for targeted gene delivery towards specific regions of the brain, which will be broadly applicable to CNS diseases. (please note this is more visionary work of my own research group)

6, Investigating Neuroestrogen Modulation on Auditory Circuit Dynamics

Hyejoo Kang; Luke Remage-Healey

Neuroscience and Behavior

Neuroestrogens, estrogens synthesized within the brain, are abundant in the forebrain auditory circuits of vocal learning species such as humans and songbirds. In humans, estrogens influence auditory perception and memory, though the specific cellular and synaptic mechanisms are not fully understood. In zebra finches, neuroestrogens are produced in the NCM (caudomedial nidopallium) in response to conspecific songs, and they rapidly enhance neuronal firing and modulate inhibitory synaptic transmission. Our ex vivo whole-cell voltage clamp recordings in the NCM, targeting distinct cell types, reveal that estrogens mainly reduce inhibitory transmission onto excitatory neurons. Additionally, blocking the G-protein coupled estrogen receptor 1 (GPER1), predominantly expressed in excitatory neuronal membranes, abolishes neuroestrogen-induced changes in synaptic transmission, indicating GPER1's critical role in these effects. To further explore these mechanisms at the level of intact in vivo circuits, we used 'Retrodrive' recordings, combining in vivo electrophysiology with retrodialysis. We observe a reduction in neuronal responses to conspecific songs during neuroestrogen synthesis blockade, while exogenous estrogens do not fully reverse these effects. Ongoing analyses are determining whether estrogen synthesis inhibition and exogenous estrogen application differ by cell type. We hypothesize that neuroestrogens selectively influence auditory coding in excitatory compared to inhibitory neurons in the NCM. Understanding how neuroestrogens impact auditory processing could illuminate fundamental sensory perception and neural circuit mechanisms.

7, Chocolate as Breakfast Speeds Up Locomotion Re-entrainment but Induces Internal Misalignment with Liver Post Jet Lag 

Zhen Nie

Neuroscience, Smith College

Working and traveling against the natural sleep-wake cycle can cause desynchrony between endogenous circadian rhythms and the outside environment, which leads to multiple negative health outcomes. Escobar et al. (2020) discovered that chocolate for breakfast with ad libitum feeding following a 6-hour shift can accelerate re-entrainment of behavior in rats. Measures of internal desynchrony (SCN c-Fos expression, glucose and triglyceride, body temperature rhythms) were also impacted. In this study, we measured activity and liver DBP-Luc rhythms of mice treated with and without chocolate breakfast before and after a 6-hour shift using an in vivo bioluminescence monitoring system (n = 8). We replicated that chocolate could advance locomotor activity re-entrainment and extend this to mice. The effect on behavioral re-entrainment (2-3 days) was greater than the more minor effect on liver re-entrainment. We conclude that mice benefit with faster behavioral adjustment, but they continue to show internal desynchrony following chocolate for breakfast.  

8, Exploring GPR12's Role in Regulating Amyloid Precursor Protein: Implications for Alzheimer's Disease

Nunez Santos, Mariela; Alphas, Stella; Silvera, Emma; Caputo, Abby; Marentes Dominguez, Montserrat; Owino, Sharon 

Neuroscience, Smith College

Alzheimer's disease (AD) is the most common form of early onset dementia, characterized by the pathological accumulation of neurofibrillary tangles and amyloid beta plaques, resulting in memory loss, behavioral changes, and cognitive impairments. In AD, G protein-coupled receptors (GPCRs) are associated with multiple stages of amyloid precursor protein (APP) proteolysis, neuroinflammation, and tau pathobiology. One of these key GPCRs is GPR3, which modulates 𝛾-secretase, leading to an increase of Aβ production. Interestingly, GPR3 shares high sequence identity with two other GPCRs known as GPR6 and GPR12. Given the sequence similarity and brain expression pattern of GPR3 and GPR12, we aimed to investigate whether GPR12 also modulates APP. In this study, we demonstrate that APP protein levels increase in the presence of GPR12 under overexpressed conditions in HEK293T and human microglia cell-line (HMC3). Additionally, we observe that GPR12 co-localizes with neurons and microglia in human AD brain samples. These findings suggest that GPR12 may play a role in regulation of APP, adding a new dimension to our understanding of AD pathogenesis.

9, Ecological Niche Holds Greater Evolutionary Weight than Phylogeny in the Experience-Dependent Development of Mammalian Visual Cortex

Aburto, P; Sudana, K; Pallas, S

Biology, UMass-Amherst

The maturation of mammalian sensory cortical networks has generally been ascribed to experience-dependent plasticity: the shaping of neural circuits through sensory inputs during critical periods. In the visual system, dark rearing (DR) disrupts the normal development of neuronal representations of visual space, known as receptive elds (RF), in the primary visual cortex (V1). However, our work suggests that nocturnal or crepuscular mammals develop mature RF properties without visual experience. Hamsters, a crepuscular species, exhibit rened V1 RFs by adolescence even if kept in the dark, but their RFs enlarge in adulthood, implicating a dependence on light for RF development but not for mature RF maintenance (Balmer & Pallas, 2015). This project characterizes V1 RF development in two more species: crepuscular ferrets and nocturnal mice. We hypothesized that ecological niche, rather than phylogenetic relations, determines the need for light exposure in development of RF properties. Nocturnal mice are thus predicted to be independent of light throughout life, but crepuscular ferrets, like hamsters, would build but not maintain their RFs if light-deprived, despite being more genetically distant. Our preliminary data support the hypothesis; ferret RF development and dependence on visual experience is similar to that of hamsters, whereas our data from nocturnal mice suggest that both renement and maintenance of RFs can occur without visual experience. Our prelimary data support the hypothesis and thus reveal that visual cortical development research on mice is less applicable to humans than research on crepuscular (and perhaps diurnal) mammals. Investigating these differences will help future researchers utilize more appropriate animal models for studying human visual development and disorders.

10, UMass Amherst Genomics Core Facility: Capabilities and Resources

Ravi Ranjan

Director, Genomics Core Facility 

The Genomics Facility provides a suite of services to address high-throughput next-generation sequencing (NGS), including solutions for sample processing such as nucleic-acid isolation, nucleic-acid quantitative and qualitative analysis, NGS library preparation, quantitative-PCR analysis, etc.

The Genomics Facility is a fee-for-service lab and provides a sample processing and library preparation such as whole genome sequencing, shotgun metagenomics, metatranscriptomics, targeted amplicon sequencing, RNA-Seq, ChIP-Seq, Exome Sequencing, 10x Single Cell Genomics, etc., to address genomics project needs. The facility accepts samples and performs requested analysis. We offer training to users to conduct experimentation for use on a fee for service basis to both internal and external researchers, academic or industry.

The Genomics Facility is equipped with - Illumina MiSeq NGS systems, 10x Genomics Chromium Controller System, Nexcelom Cellometer K2 Cell Counter, Diagenode Bioruptor Pico, Agilent 2100 Bioanalyzer, SageScience BluePippin, BioRad CFX96 Touch Real-Time PCR system, Qubit Fluorometer, Gel Electrophoresis, FastPrep 24-G Homogenizer, Savant Speed-Vac, and other ancillary lab equipment. We also facilitate high throughput NGS projects using production scale sequencers. We also facilitate molecular cloning and molecular biology projects. 

11, The Effect of Aging on Emotional Memory Encoding and Consolidation over Sleep and Wake

Rodheim, K, Jones, B, Spencer, R

Neuroscience and Behavior, UMass Amherst

Introduction: Sleep is essential for the consolidation of emotional memories. Young adults exhibit a bias towards consolidation of negative memories over sleep while older adults exhibit a bias towards consolidation of positive memories over sleep. As this parallels known biases in emotional memory encoding, it is unclear whether biases found after sleep are simply carried over from biases prior to sleep or if sleep amplifies emotional memory biases. Thus, the present study assessed emotional memory before and after intervals of sleep and wake to determine whether sleep biases the selectivity of emotional memory.

Methods: Healthy younger (N=52, 18-30 years; YA) and older adults (N=38, 50-80 years; OA) completed two conditions: a positive and negative emotional memory task. Emotional images were viewed followed by an immediate recognition assessment before overnight sleep (Sleep group; YA=29, OA=19) or before a day of wakefulness (Wake group; YA=23, OA=19). Delayed recognition was assessed approximately 12-hrs later. For the Sleep group, polysomnography was recorded. To assess differences in memory change (delayed minus immediate recognition) between condition (negative vs. positive), group (Sleep vs. Wake) and age (YA vs. OA), ANOVAs were conducted.

Results: There was a significant interaction between the effects of condition (positive vs. negative) and group (sleep vs. wake) (p=0.03) such that sleep (relative to wake) benefitted negative but not positive memories regardless of age. Investigating age groups separately, both younger (p=0.06) and older (p=0.06) adults tended to display this interaction. We next considered change in negative memory bias (negative – positive performance) between immediate and delayed recognition. There was a near-significant main effect of group (p=0.06), indicating that negative bias increased in the sleep compared to wake group.

Conclusion: These findings suggest sleep may impart a negative memory bias. This is consistent with our prior work in young adults but unexpected in older adults. This may suggest that, like young adults, healthy older adults preferentially consolidate negative over positive emotional memories during a night of sleep. Therefore, sleep-dependent emotional memory consolidation may be preserved even as sleep and memory decline with aging. Future analysis will examine associations between sleep architecture and emotional memory performance.

12, 3D EM reconstructions of neurons in the nudibranch, Berghia reveal novel ultrastructural features

Sant H, DeAmicis S, Dhiman K, Glover A, Drescher B, Wu Yuelong, Schalek R, Lichtman J, Katz P

Biology, UMass Amherst

Volume electron microscopy (vEM) exposes features of nervous systems that are inaccessible through other techniques. Here we segmented and reconstructed neurons from a vEM dataset obtained from the rhinophore ganglion (rhg) of the nudibranch mollusc, Berghia stephanieae. The rhg contains 9000 somata whose functions and axonal projections are not known. Half of the rhg including the connective to the cerebral ganglion (ceg) was serially sectioned at 33 nm thickness and imaged using SEM, generating a dataset of 2,175 sections with 4x4 nm lateral resolution. There were distinct neuropil regions including one receiving axonal projections from a peptidergic ceg neuron. We reconstructed several neurons, including one that had a soma in the rhg and an axon that projected into the connective. Its dendrites lacked vesicles but contacted many vesicle-filled presynaptic boutons. We also reconstructed an axon terminal arbor that branched profusely in the neuropil region occupied by the terminals of the peptidergic ceg neuron, which contained many vesicle-filled varicosities - likely sites of peptide release. We also found novel structures, namely independent vesicle-filled boutons that were free of axon attachments. Some, but not all of these independent boutons were surrounded by glial cells suggesting that they might be in the process of degradation. The features that we uncovered using vEM reconstruction could help generate hypotheses about the function of this enigmatic ganglion.

13, Voluntary alcohol Consumption and Cognition in Aged Female Mice

Schmitt, M; Flores-Bonilla, A; Hairston, J; Hardy, J; Alpizar, O; Naughton, E; Vazey, E; Richardson, H

NSB, UMass Amherst

Aging is associated with cognitive decline and a reduction of frontotemporal corticocortical white matter tracts. In 2022, 18.4% of those aged 60-64 and 9.7% of those 65+ reported binge drinking alcohol within the previous month. Heavy alcohol use in older populations may accelerate the loss of white matter and worsen cognitive functioning, impacting other diseases of aging including frontotemporal dementias. Oligodendrocytes (OLs) are the myelinating cells of the central nervous system, wrapping axons in the protein-lipid rich myelin sheath, speeding up signal transduction. To begin exploring the relationship between binge drinking, cognition, and OLs in older adults we tested cognitive and drinking behaviors in a double transgenic mouse reporter line that conditionally tags OL precursor cells (OPCs) with enhanced yellow fluorescent protein (eYFP) following tamoxifen administration. Seventeen-month-old Pdgfrα-CreERTM-eYFP mice (N=14) were tested for baseline cognitive functioning using the object location and novel object recognition tasks (OL/NOR). They were then injected with tamoxifen to induce Cre-recombination, followed by 10 weeks of voluntary ethanol (unsweetened 20%v/v) (n=7) or water (n=7) using a drinking in the dark (DID) model. Post-drinking OL/NOR testing was done one week following the last bout of drinking. We found that voluntary alcohol intake increased over the 10-week DID period, with individual average alcohol consumption ranging from 2.02ml/kg to 11.65ml/kg per session with a group average of 6.73 ± 3.31 ml/kg. The water group consumed from 7.74 ml/kg to 27.38 ml/kg per session with a group average of 18.53 ± 6.17 ml/kg. Baseline 24-hour NOR performance showed a robust correlation with average alcohol intake, with worse performing mice showing greater voluntary alcohol intake. Conversely, baseline levels of short-term location or recognition memory did not predict subsequent alcohol intake and those drinking levels did not relate to future cognitive performance on the OL/NOR tasks (post-alcohol). Immunohistochemical experiments using a combination of cellular markers are being used to determine if lower cognitive abilities and higher drinking are associated with delays in oligodendroglial differentiation and maturation. These studies will help shape future studies identifying predictors and consequences of late in life alcohol use.

14, Characterizing parental auditory responses to chick begging calls in biparental zebra finches (Taeniopygia guttata)

Smiley, Kristina O.; Remage-Healey, Luke 

Psychological and Brain Sciences, UMass Amherst

Parental care is a widespread phenomenon that is critical for offspring growth and survival. Sensory cues unique to dependent offspring elicit the necessary behavior from parents to care for young, but how these sounds are encoded by the brain to elicit behavioral responses is not well understood. Hormones play a crucial role in regulating parental behavior. While we know much about hormonal action in brain regions that promote parental care, we know little about how hormones affect the perception of sensory information from offspring. The hormone prolactin is essential for both maternal and paternal behavior in birds. Interestingly, prolactin receptors are also widely expressed in a higher-order region of secondary pallial cortex, the caudomedial nidopallium (NCM; analogous to the secondary auditory cortex in mammals), which is involved in the perception of complex auditory signals. Therefore, we hypothesize that prolactin elevations during parenting may support the ability to unpack and respond appropriately to offspring sensory stimuli. To begin testing this hypothesis, we characterized chick begging call structure (which stimulate chick-feeding behavior in parents) across the developmental period. In addition, we characterize parent’s auditory responses to these cues by quantifying IEG immunoreactivity responses to begging calls vs. control white noise or silence. Results from these studies will be presented and discussed. These studies will lay essential groundwork for future studies which use in-vivo electrophysiology to record parental responses during parent-offspring interactions, as well as intracranial manipulations of the prolactin receptor to test whether prolactin is involved in these key parental response behaviors.

15, Multisensory integration and multidirectional connectivity in the nervous system of a nudibranch mollusc

Tait, CC; Ramirez, MD; Katz, PS

Biology, UMass Amherst

The neuroanatomy of sensory processing shapes how an organism perceives and responds to the world. In arthropods and vertebrates, olfactory systems show convergence in their neuroanatomical organization. Primary sensory neurons project to specialized neuropils of the brain, then to other regions for higher-order processing. It is unknown if such similarities extend to molluscs. We here describe the structured neuropil regions in the brain of a nudibranch sea slug. We performed Neurobiotin tracing, immunohistochemistry, and in-situ hybridization chain reaction on the nudibranch, Berghia stephanieae. For olfaction, Berghia uses dorsal tentacles termed rhinophores. Thousands of aminergic and peptidergic primary sensory neurons project centrally through the rhinophore nerves. By filling these nerves with Neurobiotin dye, we found that sensory neuron projections follow stereotyped axonal tracts and terminate in specific locations. The presence of neurotransmitters in distinct fields across these neuropils is reminiscent of the insect mushroom body, a site for multimodal integration. Filling nerves associated with the eye and the chemotactile oral tentacle co-labeled subsets of these neuropil regions. Our results ultimately suggest that there are specific locations for bilateral, multisensory integration. Thus, as in other taxa, the nudibranch brain is a location for multisensory integration. However, we also found outgoing, efferent innervation of the rhinophores via individual peptidergic and serotonergic central neurons. A large photoreceptor in each eye projects into the rhinophores. We conclude that there is multidirectional sensory connectivity between the peripheral rhinophores and brain. This contrasts with olfactory organization in other taxa, likely with profound implications for sensory processing and behavior in nudibranchs.

16, Ionic (electric) cell-cell signaling during wound healing

Sunmin Yu

Polymer Science & Engineering, UMass Amherst

Cell extrusion is an essential process to repel mutated and damaged cells to gain tissue homeostasis in epithelial tissue. While the processes at the interface between an extruding cell and its neighbors, characterized by pulse-string and lamellipodial interactions, are well-understood, the mechanisms extending beyond the single-cell level—particularly in scenarios not governed by contact proximity—remain elusive. Here, we report that the epithelial system raises the tissue-scale grand movements to overcome the complexity of problems when the local damage becomes no longer single, but multiple and distant from each other using micro-patterned laser irradiation. The consequence is that multi-point damages merged become one spot caused by bulk elastic behaviors modulating its motion inward and outward collectively. We elucidated that those collective behaviors of the epithelial system were modulated by radial propagation of bioelectrical signals from a wound. We found the mechanosensitive calcium channels control the gradients of the bioelectric signal and frequency of the excitability, suggesting the cellular bioelectric signal is essential to drive the long-range collective extrusion of the epithelial systems.