Showing 1 - 50 of 116 Items

Date: 2019-05-01

Creator: Casey Breslow

Access: Open access

Modulation in neural systems is important for regulating physiology and behavior (Wright et al., 2010). Peptides, hormones, and amines are common neural modulators, acting on many neural systems across species. One group of neural networks that can be regulated are central pattern generators (CPGs), which generate rhythmic neural patterns, which drive behaviors (Marder and Bucher, 2001). Octopamine, and its precursor tyramine, are two amines that have been found to regulate (CPGs) across species (Cooke, 2002; Fussnecker et al., 2006). One role of octopamine in the decapod neurogenic heart is regulating the frequency and the duration of heart beats. However, the precise site of octopamine modulation within the cardiac system is not yet known (Kurumoto and Ebara, 1991). One possible site of action is the cardiac ganglion (CG), the CPG in decapod hearts. The transcripts for the enzymes required to synthesize octopamine from tyramine have been identified and localized in the CG (Christie et al., 2018). This would suggest that octopamine is produced in the CG, where it could have a direct action on those neurons, or it could be released peripherally. We have found individual variation in the response to octopamine and its precursor tyramine, and significant effects of frequency and contraction amplitude in the whole heart.

Date: 2006-07-21

Creator: Anna Selmecki, Anja Forche, Judith Berman

Access: Open access

Resistance to the limited number of available antifungal drugs is a serious problem in the treatment of Candida albicans. We found that aneuploidy in general and a specific segmental aneuploidy, consisting of an isochromosome composed of the two left arms of chromosome 5, were associated with azole resistance. The isochromosome forms around a single centromere flanked by an inverted repeat and was found as an independent chromosome or fused at the telomere to a full-length homolog of chromosome 5. Increases and decreases in drug resistance were strongly associated with gain and loss of this isochromosome, which bears genes expressing the enzyme in the ergosterol pathway targeted by azole drugs, efflux pumps, and a transcription factor that positively regulates a subset of efflux pump genes.

Date: 2019-01-01

Creator: Caroline Rice

Access: Open access

Previous studies show that active exploration of an environment contributes to spatial learning more than passive visual exposure (Chrastil & Warren, 2013; Chrastil & Warren, 2015). Active navigation and cognitive decision-making in a novel environment leads to increased spatial knowledge and memory of location compared to a passive exploration that removes the decision-making component. There is evidence of theta oscillations present in electroencephalography (EEG) recordings from the hippocampus and pre-frontal cortex (PFC). These low-frequency waves could reflect spatial navigation and memory performance, suggested by their involvement in communication between the formerly named brain regions. Through communication with the hippocampus, theta oscillations could be involved in the integration of new spatial information into memory. While undergoing EEG, subjects in this study either actively or passively explored a virtual maze, identified as the “Free” or “Guided” groups, respectively. After exploring, subjects’ spatial memory of the maze was tested through a task that required navigation from a starting object to a target object. Behavioral data show increased spatial memory for the Free group, indicated by significantly greater navigation to the correct target object in the memory task. EEG results indicate significantly greater theta oscillations in frontal regions for the Free group during the exploration phase. These results support those found in previous studies and could indicate a correlation between frontal theta oscillations during learning of novel environments and spatial memory.

• Restriction End Date: 2025-06-01

Date: 2022-01-01

Creator: Abigail Raymond

Access: Access restricted to the Bowdoin Community

• Embargo End Date: 2025-05-19

Date: 2022-01-01

Creator: Alissa Chen

Access: Embargoed

Date: 2020-01-01

Creator: Emily R Oleisky

Access: Access restricted to the Bowdoin Community

Date: 2012-02-01

Creator: Erika Nyhus, Tim Curran

Access: Open access

Dual process models suggest that recognition memory is supported by familiarity and recollection processes. Previous research administering amnesic drugs and measuring ERPs during recognition memory have provided evidence for separable neural correlates of familiarity and recollection. This study examined the effect of midazolam-induced amnesia on memory for details and the proposed ERP correlates of recognition. Midazolam or saline was administered while subjects studied oriented pictures of common objects. ERPs were recorded during a recognition test 1 day later. Subjects' discrimination of old and new pictures as well as orientation discrimination was worse when they were given midazolam instead of saline. As predicted, the parietal old/new effect was decreased with the administration of midazolam. However, weaker effects on FN400 old/new effects were also observed. These results provide converging pharmacological and electrophysiological evidence that midazolam primarily affects recollection as indexed by parietal ERP old/new effects and memory for orientation, while also exerting some weaker effects on familiarity as indexed by FN400 old/new effects. © 2011 Massachusetts Institute of Technology.

Date: 2010-09-21

Creator: Hannah R. Snyder, Natalie Hutchison, Erika Nyhus, Tim Curran, Marie T., Banich, Randall C. O'Reilly, Yuko Munakata

Access: Open access

Whether grocery shopping or choosing words to express a thought, selecting between options can be challenging, especially for people with anxiety. We investigate the neural mechanisms supporting selection during language processing and its breakdown in anxiety. Our neural network simulations demonstrate a critical role for competitive, inhibitory dynamics supported by GABAergic interneurons. As predicted by our model, we find that anxiety (associated with reduced neural inhibition) impairs selection among options and associated prefrontal cortical activity, even in a simple, nonaffective verb-generation task, and the GABA agonist midazolam (which increases neural inhibition) improves selection, whereas retrieval from semantic memory is unaffected when selection demands are low. Neural inhibition is key to choosing our words.

Date: 2022-11-15

Creator: Elizabeth R. Chrastil, Caroline Rice, Mathias Goncalves, Kylie N. Moore, Syanah C. Wynn, Chantal E. Stern, Erika Nyhus

Access: Open access

Active navigation seems to yield better spatial knowledge than passive navigation, but it is unclear how active decision-making influences learning and memory. Here, we examined the contributions of theta oscillations to memory-related exploration while testing theories about how they contribute to active learning. Using electroencephalography (EEG), we tested individuals on a maze-learning task in which they made discrete decisions about where to explore at each choice point in the maze. Half the participants were free to make active decisions at each choice point, and the other half passively explored by selecting a marked choice (matched to active exploration) at each intersection. Critically, all decisions were made when stationary, decoupling the active decision-making process from movement and speed factors, which is another prominent potential role for theta oscillations. Participants were then tested on their knowledge of the maze by traveling from object A to object B within the maze. Results show an advantage for active decision-making during learning and indicate that the active group had greater theta power during choice points in exploration, particularly in midfrontal channels. These findings demonstrate that active exploration is associated with theta oscillations during human spatial navigation, and that these oscillations are not exclusively related to movement or speed. Results demonstrating increased theta oscillations in prefrontal regions suggest communication with the hippocampus and integration of new information into memory. We also found evidence for alpha oscillations during active navigation, suggesting a role for attention as well. This study finds support for a general mnemonic role for theta oscillations during navigational learning. © 2022

Date: 2014-01-01

Creator: Anja Forche

Access: Open access

Pathogenic fungi encounter many different host environments to which they must adapt rapidly to ensure growth and survival. They also must be able to cope with alterations in established niches during long-term persistence in the host. Many eukaryotic pathogens have evolved a highly plastic genome, and large-scale chromosomal changes including aneuploidy, and loss of heterozygosity (LOH) can arise under various in vitro and in vivo stresses. Both aneuploidy and LOH can arise quickly during a single cell cycle, and it is hypothesized that they provide a rapid, albeit imprecise, solution to adaptation to stress until better and more refined solutions can be acquired by the organism. While LOH, with the extreme case of haploidization in Candida albicans, can purge the genome from recessive lethal alleles and/or generate recombinant progeny with increased fitness, aneuploidy, in the absence or rarity of meiosis, can serve as a non-Mendelian mechanism for generating genomic variation. © Springer Science+Business Media 2014.

Date: 2020-05-01

Creator: Erika Nyhus, William A. Engel, Tomas Donatelli Pitfield, Isabella M.W. Vakkur

Access: Open access

Although there has been recent interest in how mindfulness meditation can affect episodic memory as well as brain structure and function, no study has examined the behavioral and neural effects of mindfulness meditation on episodic memory. Here we present a protocol that combines mindfulness meditation training, an episodic memory task, and EEG to examine how mindfulness meditation changes behavioral performance and the neural correlates of episodic memory. Subjects in a mindfulness meditation experimental group were compared to a waitlist control group. Subjects in the mindfulness meditation experimental group spent four weeks training and practicing mindfulness meditation. Mindfulness was measured before and after training using the Five Facet Mindfulness Questionnaire (FFMQ). Episodic memory was measured before and after training using a source recognition task. During the retrieval phase of the source recognition task, EEG was recorded. The results showed that mindfulness, source recognition behavioral performance, and EEG theta power in right frontal and left parietal channels increased following mindfulness meditation training. In addition, increases in mindfulness correlated with increases in theta power in right frontal channels. Therefore, results obtained from combining mindfulness meditation training, an episodic memory task, and EEG reveal the behavioral and neural effects of mindfulness meditation on episodic memory.

Date: 2019-09-04

Creator: Erika Nyhus, William Andrew Engel, Tomas Donatelli Pitfield, Isabella Marie Wang Vakkur

Access: Open access

Mindfulness meditation has been shown to improve episodic memory and increase theta oscillations which are known to play a role in episodic memory retrieval. The present study examined the effect of mindfulness meditation on episodic memory retrieval and theta oscillations. Using a longitudinal design, subjects in the mindfulness meditation experimental group who underwent 4 weeks of mindfulness meditation training and practice were compared to a waitlist control group. During the pre-training and post-training experimental sessions, subjects completed the Five Facet Mindfulness Questionnaire (FFMQ) and studied adjectives and either imagined a scene (Place Task) or judged its pleasantness (Pleasant Task). During the recognition test, subjects decided which task was performed with each word (“Old Place Task” or “Old Pleasant Task”) or “New.” FFMQ scores and source discrimination were greater post-training than pre-training in the mindfulness meditation experimental group. Electroencephalography (EEG) results revealed that for the mindfulness meditation experimental group theta power was greater post-training than pre-training in right frontal and left parietal channels and changes in FFMQ scores correlated with changes in theta oscillations in right frontal channels (n = 20). The present results suggest that mindfulness meditation increases source memory retrieval and theta oscillations in a fronto-parietal network.

Date: 2004-06-01

Creator: Anja Forche, P. T. Magee, B. B. Magee, Georgiana May

Access: Open access

Single-nucleotide polymorphisms (SNPs) are essential tools for studying a variety of organismal properties and processes, such as recombination, chromosomal dynamics, and genome rearrangement. This paper describes the development of a genome-wide SNP map for Candida albicans to study mitotic recombination and chromosome loss. C. albicans is a diploid yeast which propagates primarily by clonal mitotic division. It is the leading fungal pathogen that causes infections in humans, ranging from mild superficial lesions in healthy individuals to severe, life-threatening diseases in patients with suppressed immune systems. The SNP map contains 150 marker sequences comprising 561 SNPs and 9 insertions-deletions. Of the 561 SNPs, 437 were transition events while 126 were transversion events, yielding a transition-to-transversion ratio of 3:1, as expected for a neutral accumulation of mutations. The average SNP frequency for our data set was 1 SNP per 83 bp. The map has one marker placed every 111 kb, on average, across the 16-Mb genome. For marker sequences located partially or completely within coding regions, most contained one or more nonsynonymous substitutions. Using the SNP markers, we identified a loss of heterozygosity over large chromosomal fragments in strains of C. albicans that are frequently used for gene manipulation experiments. The SNP map will be useful for understanding the role of heterozygosity and genome rearrangement in the response of C. albicans to host environments.

Date: 2008-05-01

Creator: Anja Forche, Kevin Alby, Dana Schaefer, Alexander D. Johnson, Judith, Berman, Richard J. Bennett

Access: Open access

Candida albicans has an elaborate, yet efficient, mating system that promotes conjugation between diploid a and α strains. The product of mating is a tetraploid a/α cell that must undergo a reductional division to return to the diploid state. Despite the presence of several "meiosis-specific" genes in the C. albicans genome, a meiotic program has not been observed. Instead, tetraploid products of mating can be induced to undergo efficient, random chromosome loss, often producing strains that are diploid, or close to diploid, in ploidy. Using SNP and comparative genome hybridization arrays we have now analyzed the genotypes of products from the C. albicans parasexual cycle. We show that the parasexual cycle generates progeny strains with shuffled combinations of the eight C. albicans chromosomes. In addition, several isolates had undergone extensive genetic recombination between homologous chromosomes, including multiple gene conversion events. Progeny strains exhibited altered colony morphologies on laboratory media, demonstrating that the parasexual cycle generates phenotypic variants of C. albicans. In several fungi, including Saccharomyces cerevisiae and Schizosaccharomyces pombe, the conserved Spo11 protein is integral to meiotic recombination, where it is required for the formation of DNA double-strand breaks. We show that deletion of SPO11 prevented genetic recombination between homologous chromosomes during the C. albicans parasexual cycle. These findings suggest that at least one meiosis-specific gene has been re-programmed to mediate genetic recombination during the alternative parasexual life cycle of C. albicans. We discuss, in light of the long association of C. albicans with warm-blooded animals, the potential advantages of a parasexual cycle over a conventional sexual cycle. © 2008 Forche et al.

Date: 2008-03-28

Creator: Francisco Barceló, José A. Periáñez, Erika Nyhus

Access: Open access

This study aimed to clarify the neural substrates of behavioral switch and restart costs in intermittently instructed task-switching paradigms. Event-related potentials (ERPs) were recorded while participants were intermittently cued to switch or repeat their categorization rule (Switch task), or else they performed two perceptually identical control conditions (NoGo and Oddball). The three tasks involved different task-sets with distinct stimulus-response associations in each, but identical visual stimulation, consisting of frequent colored shapes (p = 0.9) and randomly interspersed infrequent black shapes (p = 0.1; '+' and 'x' symbols). Behavioral restart costs were observed in the first target responses following all black shapes in the Switch and NoGo tasks - but not in the Oddball task - and corresponded with enhanced fronto-centrally distributed early cue-locked P3 activity (peak latency 325-375 ms post-cue onset at the vertex). In turn, behavioral switch costs were associated with larger late cue-locked P3 amplitudes in the Switch task only (peak latency 400-450 ms post-cue onset at mid-parietal sites). Together with our information theoretical estimations, ERP results suggested that restart and switch costs indexed two neural mechanisms related to the preparatory resolution of uncertainty: (1) the intermittent re-activation of task-set information, and (2) the updating of stimulus-response mappings within an active task set, as indexed by early and late cue-locked P3 activations, respectively. In contrast, target-locked P3 activations reflected a functionally distinct mechanism related to the implementation of task-set information. We conclude that task-switching costs consist of both switch-specific and switch-unspecific processes during the preparation and execution stages of task performance. © 2008 Barceló, Periáñez and Nyhus.

• Restriction End Date: 2025-06-01

Date: 2022-01-01

Creator: Warsameh Bulhan

Access: Access restricted to the Bowdoin Community

Date: 2023-01-01

Creator: Kenneth Garcia

Access: Open access

Neuromodulation allows for the flexibility of neural circuit dynamics and the outputs they produce. Studies of the stomatogastric nervous system (STNS) have expanded our knowledge on the actions of neuromodulators, small molecules that most often activate G-protein coupled receptors and reconfigure circuit activity and composition. In these systems, modulation has been found to occur at every level, from sensory-motor coupling to neuromuscular transmission (Harris-Warrick and Marder 1991). Neuromodulators have complex effects on motor output; they can alter the firing of individual neurons while also modulating muscle properties, neuromuscular transmission, and sensory neuron response to muscle activity (Fort et al. 2004). We investigated this further by recording the motor output produced by the gastric mill rhythm of the lobster STNS under neuromodulator conditions. How is this neuromuscular system as a whole modulated to produce motor flexibility? We hypothesized that these neuromodulators act on individual receptors of component neurons of central pattern generator (CPG)-effector system themselves and at the periphery, coordinately altering muscle contraction by altering all levels of the crustacean neuromuscular system. Application of NRNFLRFamide, RPCH, oxotremorine, and proctolin to the gastric mill 4 (gm4) muscles of the Cancer crab showed that neuromodulators that have been found to have variable, yet significant effects on the activity of the neurons of the STNS directly alter the activity of the gm4 muscles as well, suggesting that coordination of peripheral actions and direct neuronal modulation regulates patterned motor output.

• Restriction End Date: 2028-06-01

Date: 2023-01-01

Creator: Jada Scotland

Access: Access restricted to the Bowdoin Community

Date: 2023-01-01

Creator: Rowland Luo

Access: Open access

The study of neuronal development could provide foundational information on neurogenesis and neuroplasticity. The small size and relatively simple nervous system of Orthoptera make them ideal models for neurodevelopmental studies. The peripheral nervous system development is an intricate and precise process that each sensory neurons are able to reach their central nervous system partners in a relatively short amount of time. Although the peripheral nervous system in limb buds and their genetic regulations are well understood in grasshopper embryos, few studies have explored the developing nervous system in a cricket model. Therefore, the first goal of the current experiment is to characterize the normal peripheral nervous system development in cricket embryos. Previous studies in Drosophila have suggested Toll6 and Toll7 receptors could serve as important targets for the neurotrophic-like factors Spaetzle2 and 5. Malfunctioning neurotrophic pathways could lead to abnormal nervous system development. Therefore, the second goal of the current study is to explore the roles of Toll7 in the development of the cricket peripheral nervous system. Immunohistochemical staining using anti-horseradish peroxidase (Anti-HRP) was used to illustrate crickets' embryonic developing peripheral nervous system in the limb buds from developmental stage 7.0 to 11.0. Cricket eggs were injected with Toll7 double stranded RNA (dsRNA) and rhodamine dye to suppress the Toll7 mRNA level. The control eggs were injected with GFP dsRNA and rhodamine dye. The peripheral nervous system development in cricket embryos is largely homologous to that observed in grasshopper embryos. All later-emerged sensory neurons followed the pathway established by the first pioneer neuron Ti1. Ti1 made stereotypical turns following the steering signals on epithelial and guidepost cell surfaces and eventually fasciculate with lateral motor axons from the central nervous system. When examining the peripheral nervous system development with Toll7 knockdown, a decrease in limb bud volume was observed at stage 7.7 and stage 8.0, suggesting Toll7’s potential roles in aiding cell-cell intercalation processes in Orthoptera embryos. Furthermore, a delay in Ti1 pioneer neuron development was observed with Toll7 knockdown at early developmental stages, providing evidence for Toll-Spaetzle pathway’s neurotrophic-like functions. The results of the current experiment provide the first description of the peripheral nervous system development in the cricket limb buds and further evidence of Toll-Spaetzle pathway’s neurotrophic properties.

Date: 2025-01-01

Creator: Margaret Broaddus

Access: Open access

ABSTRACT CHAPTER I: All nervous systems are influenced by circulating hormones, which can modulate neural circuits to produce different outputs from the same set of neurons. Invertebrate models, particularly crustaceans, serve as excellent models for studying neuromodulation because they contain neural circuits that continue to generate fictive activity when dissected out of the animal. The stomatogastric nervous system (STNS) of the Jonah Crab (Cancer borealis) has long been used to study neuromodulation due to its well-characterized circuits. Even in such a compact neural network, little is known about how these circuits are modulated, and this remains a question in all animals, particularly in humans. Here we investigated the modulation of the pyloric circuit by applying bulk hemolymph to the dissected STNS preparation. The hemolymph contains all of the circulating modulators, some of which have known effects on the pyloric rhythm (though many are still unknown). Interestingly, when hemolymph is applied to the isolated STNS, the pyloric rhythm is suppressed. This is surprising given that in vivo the STNS is continually exposed to hemolymph (the STG is situated within an artery, and thus, exposed to circulating hemolymph) and the pyloric rhythm is constitutively active. Therefore, I hypothesized that there are synaptically released neurotransmitters that excite the pyloric rhythm. To test this hypothesis, we applied three different excitatory modulators – proctolin, serotonin, and oxotremorine – separately in the presence of hemolymph. I found that proctolin and oxotremorine restore the pyloric rhythm in the presence of hemolymph. However, serotonin did not consistently overcome the inhibition of hemolymph. ABSTRACT CHAPTER II: A plethora of work has begun to identify how endogenous neural and hormonal modulators interact to influence the pyloric network. Here we examined the modulation of the stomatogastric nervous system (STNS) via two excitatory endogenous modulators CabTRP Ia and corazonin. CabTRP Ia and corazonin both excite the pyloric rhythm, but in distinct ways. Preliminary data by Nusbaum and Christie from 2003 suggested that an initial corazonin application gated a stronger response to subsequent CabTRP Ia when compared the inverse application of these neuromodulators. We sought to validate this gating phenomenon, but found no significant difference between the effects of the first and second applications of CabTRP Ia. Given that these animals are wild caught and surviving in a changing oceanic environment, it is possible that this modulatory effect in the Jonah Crab has changed over the last few decades due to environmentally driven shifts in receptor expression and channel conductances.

Date: 2025-01-01

Creator: Aeri Ko

Access: Access restricted to the Bowdoin Community

Date: 2010-07-01

Creator: Anna Selmecki, Anja Forche, Judith Berman

Access: Open access

The genomic plasticity of Candida albicans, a commensal and common opportunistic fungal pathogen, continues to reveal unexpected surprises. Once thought to be asexual, we now know that the organism can generate genetic diversity through several mechanisms, including mating between cells of the opposite or of the same mating type and by a parasexual reduction in chromosome number that can be accompanied by recombination events (2, 12, 14, 53, 77, 115). In addition, dramatic genome changes can appear quite rapidly in mitotic cells propagated in vitro as well as in vivo. The detection of aneuploidy in other fungal pathogens isolated directly from patients (145) and from environmental samples (71) suggests that variations in chromosome organization and copy number are a common mechanism used by pathogenic fungi to rapidly generate diversity in response to stressful growth conditions, including, but not limited to, antifungal drug exposure. Since cancer cells often become polyploid and/or aneuploid, some of the lessons learned from studies of genome plasticity in C. albicans may provide important insights into how these processes occur in higher-eukaryotic cells exposed to stresses such as anticancer drugs. © 2010, American Society for Microbiology.

Date: 2018-02-01

Creator: Erika Nyhus

Access: Open access

Evidence from fMRI has consistently located a widespread network of frontal, parietal, and temporal lobe regions during episodic retrieval. However, the temporal limitations of the fMRI methodology have made it difficult to assess the transient network dynamics by which these distributed regions coordinate activity. Recent evidence suggests that beta oscillations (17-20 Hz) are important for top-down control for memory suppression. However, the spatial limitations of the EEG methodology make it difficult to assess the relationship between these oscillatory signals and the distributed networks identified with fMRI. This study used simultaneous EEG/fMRI to identify networks related to beta oscillations during episodic retrieval. Participants studied adjectives and either imagined a scene (Place Task) or judged its pleasantness (Pleasant Task). During the recognition test, participants decided which task was performed with each word (“Old Place Task” or “Old Pleasant Task”) or “New.” EEG results revealed that posterior beta power was greater for new than old words. fMRI results revealed activity in a frontal, parietal network that was greater for old than new words, consistent with prior studies. Although overall beta power increases correlated with decreased activity within a predominantly parietal network, within the right dorsolateral and ventrolateral pFC, beta power correlated with BOLD activity more under conditions requiring more cognitive control and EEG/fMRI effects in the right frontal cortex correlated with BOLD activity in a frontoparietal network. Therefore, using simultaneous EEG and fMRI, the present results suggest that beta oscillations are related to postretrieval control operations in the right frontal cortex and act within a broader postretrieval control network. © 2017 Massachusetts Institute of Technology.

Date: 2022-06-01

Creator: Syanah C. Wynn, Erika Nyhus, Ole Jensen

Access: Open access

To successfully encode information into long-term memory, we need top-down control to focus our attention on target stimuli. This attentional focus is achieved by the modulation of sensory neuronal excitability through alpha power. Failure to modulate alpha power and to inhibit distracting information has been reported in older adults during attention and working memory tasks. Given that alpha power during encoding can predict subsequent memory performance, aberrant oscillatory modulations might play a role in age-related memory deficits. However, it is unknown whether there are age-related differences in memory performance or alpha modulation when encoding targets with distraction. Here we show that both older and younger adults are able to encode targets paired with distractors and that the level of alpha power modulation during encoding predicted recognition success. Even though older adults showed signs of higher distractibility, this did not harm their episodic memory for target information. Also, we demonstrate that older adults only modulated alpha power during high distraction, both by enhancing target processing and inhibiting distractor processing. These results indicate that both younger and older adults are able to employ the same inhibitory control mechanisms successfully, but that older adults fail to call upon these when distraction is minimal. The findings of this study give us more insight into the mechanisms involved in memory encoding across the lifespan. © 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Date: 2019-01-01

Creator: Louis Mendez

Access: Open access

Central pattern generators (CPGs) are neural networks that generate rhythmic motor patterns to allow organisms to perform stereotypical tasks, such as breathing, scratching, flying, and walking. The American lobster, Homarus americanus, is a simple model system whose CPGs are functionally analogous to those in vertebrate models and model complex rhythmic behaviors. CPGs in many Crustacea, including the American lobster, have been studied because of their ability to maintain biological function after isolation in physiologically relevant conditions. The cardiac ganglion (CG) is a CPG consisting of five larger motor neurons and four smaller pacemaker neurons that innervate the cardiac neuromuscular system and generate electrical bursts that drive patterned behaviors. Neuromodulators, such as neuropeptides, are known to modulate neural output in the CPGs of the American lobster. Currently, neuromodulators affecting the cardiac ganglia are thought to be mainly expressed and secreted outside of the cardiac ganglia, acting as extrinsic neuromodulators. However, there is current evidence to support the idea that neuromodulators can be intrinsically expressed within the cardiac ganglion of the American lobster. Preliminary studies using transcriptomic techniques on genomic and transcriptomic information indicate that neuropeptides are likely expressed within the cardiac ganglion. However, little research has been done to determine whether these neuropeptides are expressed in the cardiac ganglion of the American lobster. Therefore, the purpose of this study is to combine bioinformatics and mass spectrometric techniques to determine whether select neuropeptides are present in the cardiac ganglion within the cardiac neuromuscular system of the American lobster, Homarus americanus. Our data mining techniques using protein query sequences obtained from previously annotated brain and eyestalk transcriptomes resulted in the identification of 22 putative neuropeptides preprohormones from 17 neuropeptide families and 20 putative neuropeptide receptors from 17 neuropeptide receptor families in the CG transcriptome. Additionally, 9 putative neuropeptide receptors from 7 neuropeptide receptor families were detected in the cardiac muscle transcriptome. Of the 17 neuropeptide families detected, receptors for 9 of these neuropeptide families were detected in the CG transcriptome. Receptors for 6 of the neuropeptide families were also present in the cardiac muscle transcriptome. Interestingly, receptors for 6 of neuropeptide families detected were not found in either the CG or cardiac muscle transcriptomes, and receptors for 4 neuropeptide families that weren’t detected in the CG transcriptome were found in the cardiac muscle transcriptome. Therefore, our research suggests that neuropeptides are able to modulate CPG activity extrinsically, either though hormonal or local delivery, or intrinsically. Additionally, neuropeptides were extracted from the stomatogastric ganglion and the commissural ganglion using a scaled-down neuropeptide extraction protocol to estimate the number of tissues required to obtain sufficiently strong mass spectrometry signals. Pooled samples with two commissural ganglia and single samples of a commissural ganglion and a stomatogastric ganglion displayed little signal and an increase in larger peptides and impurities relative to single-tissue samples. Therefore, further optimization of the scaled-down neuropeptide extraction protocol must be done prior to analysis of a cardiac ganglion in the American lobster.

Date: 2020-01-01

Creator: Felicia F. Wang

Access: Access restricted to the Bowdoin Community

Date: 2020-01-01

Creator: William Allen

Access: Open access

Central pattern generators (CPGs) are neural circuits whose component neurons possess intrinsic properties and synaptic connections that allow them to generate rhythmic motor outputs in the absence of descending inputs. The cardiac ganglion (CG) is a nine-cell CPG located in the American lobster, Homarus americanus. Stretch of the myocardium feeds back to the CG through mechano-sensitive dendrites and is thought to play a role in maintaining regularity in the beating pattern of the heart. The novel peptide AMGSEFLamide has been observed to induce irregular beating patterns when applied at high concentrations. This study investigated the interaction between stretch-related feedback and AMGSEFLamide modulation in generating irregular beating patterns in the whole heart of Homarus americanus. It was hypothesized that greater longitudinal stretch of the heart would result in greater regularity in the instantaneous beat frequency, based on previous findings that stretch-sensitive dendrites play a role in the regulation of the heartbeat. Furthermore, it was predicted that the elimination of stretch feedback via deafferentation of the heart would augment the irregularity induced by AMGSEFLamide. Data showed significantly increased irregularity in beating in response to 10-6 M AMGSEFLamide application. Longitudinal stretch did not reliably alter baseline variability in frequency, nor did it influence the modulatory effect of AMGSEFLamide. Deafferentation did not significantly alter baseline irregularity. Deafferented preparations did exhibit a trend of responding to AMGSEFLamide with a greater percent increase in irregularity compared to when afferents were intact, suggesting a potential role of stretch-stabilization in response to modulatory perturbations in the Homarus heart.

Date: 2020-01-01

Creator: Jacob Salman Kazmi

Access: Open access

Neuromodulation may be a substrate for the evolution of behavioral diversity. The extent to which a central pattern generator is modulated could serve as a mechanism that enables variability in motor output dependent on an organism’s need for behavioral flexibility. The pyloric circuit, a central pattern generator in the crustacean stomatogastric nervous system (STNS), stimulates contractions of foregut muscles in digestion. Since neuromodulation enables variation in the movements of pyloric muscles, more diverse feeding patterns should be correlated with a higher degree of STNS neuromodulation. Previous data have shown that Cancer borealis, an opportunistic feeder, is sensitive to a wider array of neuromodulators than Pugettia producta, a specialist feeder. The observed difference in modulatory capacity may be coincidental since these species are separated by phylogeny. We predict that the difference in modulatory capacity is a product of a differential need for variety in foregut muscle movements. This study examined two members of the same superfamily as P. producta, the opportunistically feeding snow crab (Chionoecetes opilio) and portly spider crab (Libinia emarginata). Using extracellular recording methods, the responses of isolated STNS preparations to various neuromodulators were measured. Initial qualitative results indicate that the STNS of C. opilio is sensitive to all of these neuromodulators. Additionally, previous data on the neuromodulatory capacity of L. emarginata was supported through similar electrophysiological analysis of the isolated STNS. As a first step in determining the mechanism of differential sensitivity between species, tissue-specific transcriptomes were generated and mined for neuromodulators.

Date: 2020-01-01

Creator: Marie Marjorie Bergsund

Access: Access restricted to the Bowdoin Community

Date: 2023-01-01

Creator: Khushali N Patel

Access: Access restricted to the Bowdoin Community

Date: 2023-01-01

Creator: Lucia Marie O'Sullivan

Access: Access restricted to the Bowdoin Community

Date: 2025-01-01

Creator: Samantha McLemore

Access: Access restricted to the Bowdoin Community

Date: 2024-01-01

Creator: Zackery D. Reynolds

Access: Access restricted to the Bowdoin Community

Date: 2016-05-01

Creator: Michael M Kang

Access: Access restricted to the Bowdoin Community

Date: 2014-12-01

Creator: Anja Wartenberg, Jörg Linde, Ronny Martin, Maria Schreiner, Fabian, Horn, Ilse D. Jacobsen, Sabrina Jenull, Thomas Wolf, Karl Kuchler, Reinhard Guthke, Oliver Kurzai, Anja Forche, Christophe d'Enfert, Sascha Brunke, Bernhard Hube

Access: Open access

Following antifungal treatment, Candida albicans, and other human pathogenic fungi can undergo microevolution, which leads to the emergence of drug resistance. However, the capacity for microevolutionary adaptation of fungi goes beyond the development of resistance against antifungals. Here we used an experimental microevolution approach to show that one of the central pathogenicity mechanisms of C. albicans, the yeast-to-hyphae transition, can be subject to experimental evolution. The C. albicans cph1Δ/efg1Δ mutant is nonfilamentous, as central signaling pathways linking environmental cues to hyphal formation are disrupted. We subjected this mutant to constant selection pressure in the hostile environment of the macrophage phagosome. In a comparatively short time-frame, the mutant evolved the ability to escape macrophages by filamentation. In addition, the evolved mutant exhibited hyper-virulence in a murine infection model and an altered cell wall composition compared to the cph1Δ/efg1Δ strain. Moreover, the transcriptional regulation of hyphae-associated, and other pathogenicity-related genes became re-responsive to environmental cues in the evolved strain. We went on to identify the causative missense mutation via whole genome- and transcriptome-sequencing: a single nucleotide exchange took place within SSN3 that encodes a component of the Cdk8 module of the Mediator complex, which links transcription factors with the general transcription machinery. This mutation was responsible for the reconnection of the hyphal growth program with environmental signals in the evolved strain and was sufficient to bypass Efg1/Cph1-dependent filamentation. These data demonstrate that even central transcriptional networks can be remodeled very quickly under appropriate selection pressure.

• Restriction End Date: 2025-06-01

Date: 2020-01-01

Creator: Rhianna J Patel

Access: Access restricted to the Bowdoin Community

Date: 2024-01-01

Creator: Karin van Hassel

Access: Open access

The cardiac ganglion (CG) is a central pattern generator, a neural network that, when activated, produces patterned motor outputs such as breathing and walking. The CG induces the heart contractions of the American lobster, Homarus americanus, making the lobster heart neurogenic. In the American lobster, the CG is made up of nine neurons: four premotor pacemaker neurons that send signals to five motor neurons, causing bursts of action potentials from the motor neurons. These bursts cause cardiac muscle contractions that vary in strength based on the burst duration, frequency, and pattern. The activity of the CG is modulated by feedback pathways and neuromodulators, allowing for flexibility in the CG’s motor output and appropriate responses to changes in the animal’s environment. Two feedback pathways modulate the CG motor output, the excitatory cardiac muscle stretch and inhibitory nitric oxide feedback pathways. Despite our knowledge of the modulation of the CG by feedback pathways and neuromodulators separately, little is known about how neuromodulators influence the sensory feedback response to cardiac muscle stretch. I found one neuromodulator to modulate each phase of the stretch response differently, one neuromodulator to generally not affect the stretch response, and three neuromodulators to suppress the stretch response. These results suggest neuromodulators can act to produce flexibility in a CPG’s motor output, allowing the system to respond appropriately to changes in an organism’s environment, and allow for variation in CPG responses to different stimuli.

Date: 2023-01-01

Creator: Jackie Seddon

Access: Open access

Neuromodulation, the process of altering the electrical outputs of a neuron or neural circuit, allows an organism to control its physiological processes to meet the needs of both its internal and external environments. Previous work shows that the pyloric pattern of the kelp crab (Pugettia producta) stomatogastric nervous system (STNS) neurons responded to fewer neuromodulators than the Jonah crab (Cancer borealis). Since the kelp crab diet primarily eats kelp, it is possible that the movements of the foregut that control digestion may require less flexibility in functional output compared to an opportunistic feeder. To determine whether a reduced flexibility is correlated with diet, this study compared the modulatory responses in Pugettia to two other species of majoid crabs: Chionoecetes opilio and Libinia emarginata, which are both opportunistic feeders. Pooled data for this study found that Libinia and Chionoecetes responded to all twelve modulators tested. When considering the effect of modulators on stomatogastric ganglion (STG) motor outputs, we must consider whether these modulators also alter the excitatory junction potentials (EJPs) at the neuromuscular junction (NMJ), and whether there are differences in responses across species. To test this, the dorsal gastric nerve (dgn) was stimulated while recording intracellularly from the muscle fibers of the associated gm4 muscles. The NMJ of the gm4 in Cancer borealis did not appear to be broadly modulated, as only RPCH and CabTRP showed increases in amplitude, and RPCH decreased facilitation at 5 Hz.

• Embargo End Date: 2026-05-18

Date: 2023-01-01

Creator: Violet Louise Rizzieri

Access: Embargoed

Date: 2024-01-01

Creator: Nuanxi (Sissi) Feng

Access: Access restricted to the Bowdoin Community

Date: 2016-05-01

Creator: Tess Lameyer

Access: Access restricted to the Bowdoin Community

Date: 2025-01-01

Creator: Emma F.B. Gibbens

Access: Access restricted to the Bowdoin Community

Date: 2013-10-01

Creator: Brendan Eliot Depue, Nick Ketz, Matthew V. Mollison, Erika Nyhus, Marie T. Banich, Tim Curran

Access: Open access

Although investigations of memory and the dynamics of ERP components and neural oscillations as assessed through EEG have been well utilized, little research into the volitional nature of suppression over memory retrieval have used these methods. Oscillation analyses conducted on the Think/No-Think (TNT) task and volitional suppression of retrieval are of interest to broaden our knowledge of neural oscillations associated not only during successful memory retrieval but also when retrieval is unwanted or suppressed. In the current study, we measured EEG during a TNT task and performed ERP and EEG spectral power band analyses. ERP results replicated other researchers' observations of increases in 500-800 msec parietal effects for items where retrieval was instructed to be elaborated compared with being suppressed. Furthermore, EEG analyses indicated increased alpha (8-12 Hz) and theta (3-8 Hz) oscillations across parietal electrodes for items that were instructed to be suppressed versus those to be elaborated. Additionally, during the second half of the experiment (after repeated attempts at control), increases in theta oscillations were found across both frontal and parietal electrodes for items that were instructed to be suppressed and that were ultimately forgotten versus those ultimately remembered. Increased alpha power for items that were instructed to be suppressed versus elaborated may indicate reductions of retrieval attempts or lack of retrieval success. Increased theta power for items that were instructed to be suppressed versus elaborated may indicate increased or prolonged cognitive control to monitor retrieval events. © 2013 Massachusetts Institute of Technology.

Date: 2019-05-01

Creator: Katharine Torrey

Access: Open access

The peptide vasotocin (VT) and its mammalian homologue, vasopressin (VP), produce effects on social behavior that are highly species- and context-specific. We recently sequenced two genes for V1a-like receptors (VTR) in the goldfish brain, one that encodes for a fully-functioning canonical receptor and one that encodes for a non-functional truncated receptor. The current study is an investigation of whether social context may alter expression of these receptor types and thus, potentially, behavioral responses to VT. We used western blotting and immunohistochemistry with custom anti-VTR antibodies to characterize the distribution of VTR throughout the forebrain and the hindbrain. Western blot results showed bands close to the predicted sizes for truncated and canonical VTR constructs, suggesting that both genes are translated into protein in the brain, but the presence of additional bands suggested potential nonspecific binding. Immunohistochemistry data revealed VTR signal throughout the brain in regions associated with social behavior. We additionally examined whether visual and olfactory context alters behavioral responsiveness to VT, potentially by altering the expression of one or both receptors. Behavioral tests suggested that VT inhibits approach to males, but its effect on response to females in reproductive contexts is still undetermined, likely due to interference from a stress response during testing. Further characterization of VTR throughout the brain will clarify how social context might alter VT signaling through context-dependent modulation of its receptors. Additionally, future work should examine the behavioral consequences of such modulation by further studying whether VT’s effect on social approach behavior depends on context.

Date: 2011-01-01

Creator: A. Forche, D. Abbey, T. Pisithkul, M. A. Weinzierl, T., Ringstrom, D. Bruck, K. Petersen, J. Berman

Access: Open access

Genetic diversity is often generated during adaptation to stress, and in eukaryotes some of this diversity is thought to arise via recombination and reassortment of alleles during meiosis. Candida albicans, the most prevalent pathogen of humans, has no known meiotic cycle, and yet it is a heterozygous diploid that undergoes mitotic recombination during somatic growth. It has been shown that clinical isolates as well as strains passaged once through a mammalian host undergo increased levels of recombination. Here, we tested the hypothesis that stress conditions increase rates of mitotic recombination in C. albicans, which is measured as loss of heterozygosity (LOH) at specific loci. We show that LOH rates are elevated during in vitro exposure to oxidative stress, heat stress, and antifungal drugs. In addition, an increase in stress severity correlated well with increased LOH rates. LOH events can arise through local recombination, through homozygosis of longer tracts of chromosome arms, or by whole-chromosome homozygosis. Chromosome arm homozygosis was most prevalent in cultures grown under conventional lab conditions. Importantly, exposure to different stress conditions affected the levels of different types of LOH events, with oxidative stress causing increased recombination, while fluconazole and high temperature caused increases in events involving whole chromosomes. Thus, C. albicans generates increased amounts and different types of genetic diversity in response to a range of stress conditions, a process that we term "stress-induced LOH" that arises either by elevating rates of recombination and/or by increasing rates of chromosome missegregation. IMPORTANCE Stress-induced mutagenesis fuels the evolution of bacterial pathogens and is mainly driven by genetic changes via mitotic recombination. Little is known about this process in other organisms. Candida albicans, an opportunistic fungal pathogen, causes infections that require adaptation to different host environmental niches. We measured the rates of LOH and the types of LOH events that appeared in the absence and in the presence of physiologically relevant stresses and found that stress causes a significant increase in the rates of LOH and that this increase is proportional to the degree of stress. Furthermore, the types of LOH events that arose differed in a stress-dependent manner, indicating that eukaryotic cells generate increased genetic diversity in response to a range of stress conditions. We propose that this "stress-induced LOH" facilitates the rapid adaptation of C. albicans, which does not undergo meiosis, to changing environments within the host. © 2011 Forche et al.

Date: 2007-10-01

Creator: Alix Coste, Anna Selmecki, Anja Forche, Dorothée Diogo, Marie Elisabeth, Bougnoux, Christophe D'Enfert, Judith Berman, Dominique Sanglard

Access: Open access

TAC1 (for transcriptional activator of CDR genes) is critical for the upregulation of the ABC transporters CDR1 and CDR2, which mediate azole resistance in Candida albicans. While a wild-type TAC1 allele drives high expression of CDR1/2 in response to inducers, we showed previously that TAC1 can be hyperactive by a gain-of-function (GOF) point mutation responsible for constitutive high expression of CDR1/2. High azole resistance levels are achieved when C. albicans carries hyperactive alleles only as a consequence of loss of heterozygosity (LOH) at the TAC1 locus on chromosome 5 (Chr 5), which is linked to the mating-type-like (MTL) locus. Both are located on the Chr 5 left arm along with ERG11 (target of azoles). In this work, five groups of related isolates containing azole-susceptible and -resistant strains were analyzed for the TAC1 and ERG11 alleles and for Chr 5 alterations. While recovered ERG11 alleles contained known mutations, 17 new TAC1 alleles were isolated, including 7 hyperactive alleles with five separate new GOF mutations. Single-nucleotide- polymorphism analysis of Chr 5 revealed that azole-resistant strains acquired TAC1 hyperactive alleles and, in most cases, ERG11 mutant alleles by LOH events not systematically including the MTL locus. TAC1 LOH resulted from mitotic recombination of the left arm of Chr 5, gene conversion within the TAC1 locus, or the loss and reduplication of the entire Chr 5. In one case, two independent TAC1 hyperactive alleles were acquired. Comparative genome hybridization and karyotype analysis revealed the presence of isochromosome 5L [i(5L)] in two azole-resistant strains. i(5L) leads to increased copy numbers of azole resistance genes present on the left arm of Chr 5, among them TAC1 and ERG11. Our work shows that azole resistance was due not only to the presence of specific mutations in azole resistance genes (at least ERG11 and TAC1) but also to their increase in copy number by LOH and to the addition of extra Chr 5 copies. With the combination of these different modifications, sophisticated genotypes were obtained. The development of azole resistance in C. albicans is therefore a powerful instrument for generating genetic diversity. Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Date: 2019-05-01

Creator: Anja Forche, Norma V. Solis, Marc Swidergall, Robert Thomas, Alison, Guyer, Annette Beach, Gareth A. Cromie, Giang T. Le, Emily Lowell, Norman Pavelka, Judith Berman, Aimeé M. Dudley, Anna Selmecki, Scott G. Filler

Access: Open access

When the fungus Candida albicans proliferates in the oropharyngeal cavity during experimental oropharyngeal candidiasis (OPC), it undergoes large-scale genome changes at a much higher frequency than when it grows in vitro. Previously, we identified a specific whole chromosome amplification, trisomy of Chr6 (Chr6x3), that was highly overrepresented among strains recovered from the tongues of mice with OPC. To determine the functional significance of this trisomy, we assessed the virulence of two Chr6 trisomic strains and a Chr5 trisomic strain in the mouse model of OPC. We also analyzed the expression of virulence-associated traits in vitro. All three trisomic strains exhibited characteristics of a commensal during OPC in mice. They achieved the same oral fungal burden as the diploid progenitor strain but caused significantly less weight loss and elicited a significantly lower inflammatory host response. In vitro, all three trisomic strains had reduced capacity to adhere to and invade oral epithelial cells and increased susceptibility to neutrophil killing. Whole genome sequencing of pre- and post-infection isolates found that the trisomies were usually maintained. Most post-infection isolates also contained de novo point mutations, but these were not conserved. While in vitro growth assays did not reveal phenotypes specific to de novo point mutations, they did reveal novel phenotypes specific to each lineage. These data reveal that during OPC, clones that are trisomic for Chr5 or Chr6 are selected and they facilitate a commensal-like phenotype.

Date: 2020-01-01

Creator: Julianne Scholes

Access: Access restricted to the Bowdoin Community

Date: 2018-02-13

Creator: Robert S. Ross, Andrew Smolen, Tim Curran, Erika Nyhus

Access: Open access

A critical problem for developing personalized treatment plans for cognitive disruptions is the lack of understanding how individual differences influence cognition. Recognition memory is one cognitive ability that varies from person to person and that variation may be related to different genetic phenotypes. One gene that may impact recognition memory is the monoamine oxidase A gene (MAO-A), which influences the transcription rate of MAO-A. Examination of how MAO-A phenotypes impact behavioral and event-related potentials (ERPs) correlates of recognition memory may help explain individual differences in recognition memory performance. Therefore, the current study uses electroencephalography (EEG) in combination with genetic phenotyping of the MAO-A gene to determine how well-characterized ERP components of recognition memory, the early frontal old/new effect, left parietal old/new effect, late frontal old/new effect, and the late posterior negativity (LPN) are impacted by MAO-A phenotype during item and source memory. Our results show that individuals with the MAO-A phenotype leading to increased transcription have lower response sensitivity during both item and source memory. Additionally, during item memory the left parietal old/new effect is not present due to increased ERP amplitude for correct rejections. The results suggest that MAO-A phenotype changes EEG correlates of recognition memory and influences how well individuals differentiate between old and new items.

Date: 2009-08-04

Creator: Erika Nyhus, Tim Curran

Access: Open access

The present experiments examined how semantic vs. perceptual encoding and perceptual match affect the processes involved in recognition memory. Experiment 1 examined the effects of encoding task and perceptual match between study and test fonts on recognition discrimination for words. Font fan was used to determine the effect of distinctiveness on perceptual match. The semantic encoding task and perceptual match for distinctive items led to better recognition memory. Event-related brain potentials (ERPs) recorded from the human scalp during recognition memory experiments have revealed differences between old (studied) and new (not studied) items that are thought to reflect the activity of memory-related brain processes. In Experiment 2, the semantic encoding task and perceptual match for distinctive words led to better recognition memory by acting on both familiarity and recollection processes, as purportedly indexed by the FN400 and parietal old/new effects. Combined these results suggest that the semantic encoding task and perceptual match for distinctive items aid recognition memory by acting on both familiarity and recollection processes. © 2009 Elsevier B.V. All rights reserved.