1,720,970 research outputs found
Motor Memory Consolidation Depends on the Post-Learning Activity of Ventral Tegmental Area Dopaminergic Neurons
No full textMotor memory consolidation is ubiquitous in our daily lives, yet the underlying mechanisms remain largely elusive. It is well-established that sleep benefits memory consolidation, including motor memories. While the activity of dopaminergic neurons in the ventral tegmental area (VTADA) has been implicated in motor learning, its role in motor memory consolidation during sleep has not been clearly determined. My thesis research aims to bridge this knowledge gap. Initially, I developed a modified balance-beam task for mice to assess motor learning. I found that mice demonstrate overall improvement in motor performance across training days, with the most significant improvement occurring between the first and second days. To determine the necessity of VTADA signaling during sleep for motor memory consolidation, I chemogenetically inhibited VTADA neurons during the sleep phase following the first training day in hM4Di-expressing mice (n = 10 mice of both sexes). I found that the inhibition significantly reduced the rate of improvement in experimental mice compared to control mCherry-expressing mice (n = 9 mice). To discern whether this suppression of performance was due to impaired consolidation or stemmed from a reduced motivation to complete the task or diminished motor performance, I inhibited VTADA neurons in 'expert' mice (n = 12 mice). Notably, once motor skills were fully acquired, inhibiting VTADA neurons had no impact on motor performance. My findings strongly suggest that VTADA neurons play a crucial role in the processes of motor memory consolidation during sleep. My research is set to significantly advance the current understanding of motor memory consolidation, with the potential to inform clinical strategies aimed at improving motor function in various disabilities.Honors (Bachelor's)PsychologyUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/193948/1/eche.pd
The Gating and Maintenance of Sleep and Wake: New Circuits and Insights
No full textThis eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac
The Gating and Maintenance of Sleep and Wake: New Circuits and Insights
No full textThis eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac
Understanding Behavioral and Physiological Outcomes of Variation in Maternal Care and Glucocorticoids
Get PDFBehavior is one of the most immediate and effective ways to respond to and cope with environmental and social stressors. Our behavioral response to stressors is proposed to be intimately linked to our hormonal stress response in a bidirectional relationship. Understanding the relationship between these two stress responses in adults and their ontogeny in juveniles helps us understand how animals will respond to rapidly changing environmental pressures and provide more context for understanding the role of individual variation in behavior in natural selection. To investigate this question, I collected hormonal and behavioral data from a wild population of North American red squirrels (Tamiasciurus hudsonicus) in Yukon Territory, Canada. Red squirrels in this region have proven to be amenable to large scale experimental hormone manipulations and offspring growth, hormones, and behavior can be tracked for the entire life of hundreds of individuals each year. Using long-term data on behavior and fecal cortisol, I found no relationship between the hormonal and behavioral stress response as was measured. To better understand the ontogeny of this lack of relationship between the stress responses, I examined the role of the maternal early life environment. Maternal behavior and physiology influence the development of phenotypes, many of which are closely related to fitness. However, maternal behavior is often difficult to observe and measure in wild animals, particularly small mammals. To tackle this problem, I measured maternal motivation by recording the time until mothers return to their pups following researchers removing and returning the pups in the nest, or a “simulated predator intrusion”. I found wide variation in the behavioral response of mothers to this nest intrusion. Some mothers were very vocal and aggressively attempt to protect their pups, other moms hung out in a nearby tree and eat quietly waited for us to return their pups. I found a mother’s maternal style, as measured by latency to return to pups following the intrusion, was repeatable within individuals and played a role in increasing the survival and growth rate of offspring. To further explore the impact of the maternal environment on offspring, I tested hypotheses about the impact of maternal glucocorticoid levels on offspring behavior and physiology by conducting a manipulation with mothers across three years to experimentally elevate circulating glucocorticoids in pregnant or lactating mothers. In offspring from these mothers, I found the behavioral traits of activity and aggression in these juveniles were linked to their hormonal stress reactivity, unlike the adults. Through these studies, I expanded on our understanding of the relationship between behavior and physiology, with a particular focus on maternal effects, in a wild small mammal. I added to the growing body of evidence showing a lack of relationship between behavioral and physiological stress responses in wild animals, suggesting the need to develop a more generalizable model of the relationship between the glucocorticoids and animal personality. Furthermore, I leveraged our ability to closely track reproduction in red squirrels to empirically assess the fitness consequences of individual variation in maternal behavior and conduct a unique field experiment to branch across developmental biology, behavioral ecology, and behavioral endocrinology.PhDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/155083/1/westse_1.pd
Neurophysiological and behavioral synchronization in group-living and sleeping mice
No full textSocial interactions profoundly influence animal development, physiology, and behavior. Yet, how sleep-a central behavioral and neurophysiological process-is modulated by social interactions is poorly understood. Here, we characterized sleep behavior and neurophysiology in freely moving and co-living mice under different social conditions. We utilized wireless neurophysiological devices to simultaneously record multiple individuals within a group for 24 h, alongside video acquisition. We first demonstrated that mice seek physical contact before sleep initiation and sleep while in close proximity to each other (hereafter, "huddling"). To determine whether huddling during sleep is a motivated behavior, we devised a novel behavioral apparatus allowing mice to choose whether to sleep in close proximity to a conspecific or in solitude, under different environmental conditions. We also applied a deep-learning-based approach to classify huddling behavior. We demonstrate that mice are willing to forgo their preferred sleep location, even under thermoneutral conditions, to gain access to social contact during sleep. This strongly suggests that the motivation for prolonged physical contact-which we term somatolonging-drives huddling behavior. We then characterized sleep architecture under different social conditions and uncovered a social-dependent modulation of sleep. We also revealed coordination in multiple neurophysiological features among co-sleeping individuals, including in the timing of falling asleep and waking up and non-rapid eye movement sleep (NREMS) intensity. Notably, the timing of rapid eye movement sleep (REMS) was synchronized among co-sleeping male siblings but not co-sleeping female or unfamiliar mice. Our findings provide novel insights into the motivation for physical contact and the extent of social-dependent plasticity in sleep.Fil: Sotelo, María Inés. Universidad de Buenos Aires. Facultad de Psicología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of Michigan; Estados UnidosFil: Markunas, Chelsea. University of Michigan; Estados UnidosFil: Kudlak, Tyler. University of Michigan; Estados UnidosFil: Kohtz, Chani. University of Michigan; Estados UnidosFil: Vyssotski, Alexei L.. Universitat Zurich; SuizaFil: Rothschild, Gideon. University of Michigan; Estados UnidosFil: Eban Rothschild, Ada. University of Michigan; Estados Unido
Sex-Specific Roles for Melanin-Concentrating Hormone Neurons Linking the Neuroendocrine Reproductive Axis and Sleep
No full textMy dissertation research has centered around three aspects of reproductive physiology and the role of MCH neurons therein: lactation, the regulation of pubertal timing and fertility, and the effect of gonadal steroids on sleep architecture. Underlying and uniting these distinct elements is a focus on the transcriptional heterogeneity of MCH cells.
Chapter 1 will provide background on MCH and its role in sleep, metabolism, and reproductive physiology. In Chapters 2-5, I focus on the fast neurotransmitter content of MCH cells: most fundamentally, what is the neurochemical identity of different populations of MCH neurons? What are the effects of isolating and disrupting fast neurotransmitter co-release from MCH neurons? Finally, can a consideration of the effects not just of the MCH peptide itself, but coreleased neurotransmitters, help to disambiguate some of the seemingly disparate functions of these neurons within the neuroendocrine reproductive axis? In Chapter 6, I consider additional key transcripts beyond the machinery of classical neurotransmission to define subsets of the MCH neuron population and probe their ability to affect the relationship between the sex steroid milieu and sleep. Finally, in Chapter 7, I will integrate the findings of the former chapters and situate them in the broader context of the MCH field, discuss the strengths and weaknesses of my studies, and outline future directions for this work.PhDNeuroscienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/176466/1/bgbeekly_1.pd
Limbic Generators of Incentive Motivation and Aversive Motivation
Get PDFStriatal-level structures such as the nucleus accumbens (NAc) and central amygdala (CeA) are capable of generating intense incentive and aversive motivated behaviors (Baumgartner et al. 2020; Warlow et al. 2020). NAc may have two modes for motivation, as inhibition and excitation of NAc can both produce motivated behaviors. For example, NAc medial shell inhibition through AMPA receptor antagonist (DNQX) microinjections can produce both intense eating and defensive behaviors (Baumgartner et al., 2020). Chapter 2 of this dissertation investigates the inhibition hypothesis of accumbens motivation generation by testing whether local pairing of optogenetic excitation can disrupt ‘desire’ and ‘dread’ behaviors generated by DNQX microinjections.
Incentive and aversive motivation generated by NAc and other limbic structures are flexible and able to respond to external stressors. Chapter 3 therefore investigates a previously untested neuronal population in NAc that expresses corticotropin-releasing factor (CRF), a stress-related peptide heavily implicated in aversive motivation and distressing drug-withdrawal states in CeA and bed nucleus of stria terminalis (BNST). Like NAc, the CeA is also capable of producing intense positive and negative motivated behaviors and we investigate the flexibility of incentive or aversive motivation in CRF neurons using new Crh-Cre+ rats to optogenetically stimulate NAc, CeA, or BNST CRF-containing neurons. This work finds that excitation of CRF-expressing neurons is capable of biasing and amplifying motivation for sucrose rewards in both NAc shell and lateral CeA (Baumgartner et al. 2021). Conversely, it also demonstrates that optogenetic excitation of pallidal-like bed nucleus of stria terminalis (BNST) CRF-containing neurons produces only negative affect and aversive motivation, filling the traditional role that CRF has been hypothesized to play in aversive withdrawal and affect (Koob 2013).
Following the demonstrated positive role of NAc and CeA CRF-containing neurons for sucrose rewards, Chapter 4 of this dissertation examines whether this influence on incentive motivation also applies to drug rewards. CRF in CeA and BNST is posited to underlie aversive withdrawal states, causing negative distress that leads to addictive relapse through attempts at hedonic self-medication to relieve this state (Koob 2013). Chapter 4 therefore tests whether optogenetic excitation of CRF neurons in NAc, CeA, and BNST are capable of biasing and amplifying motivation for self-administered intravenous cocaine infusions. Understanding whether CRF-mediated incentive motivation also can drive drug motivation is therefore integral. We find that NAc and CeA CRF-expressing neurons are indeed capable of biasing motivation for cocaine infusions, while rats given the option between BNST CRF-containing neuron-paired cocaine and cocaine alone show no drug escalation or preferences between cocaine options.
Altogether this dissertation demonstrates the limbic generation of intense motivation in structures such as NAc and CeA, and how both incentive and aversive motivation can be modulated by stress and brain CRF systems. The neural mechanisms underlying these different motivational valences provide important insight into cases where motivation can become pathological, such as in addiction, schizophrenia, and other psychological disorders.PhDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/167963/1/hmbaum_1.pd
Sleep as a Modifiable Determinant of Gender, Racial, and Intersectional Disparities in Cognitive Aging
No full textSleep problems, such as insomnia and sleep apnea, have been associated with increased risk for cognitive impairment and dementia in later life; however, considerable heterogeneity in the presentation of sleep problems has made it difficult to pinpoint the specific mechanisms underlying sleep—cognition associations. Moreover, convergent health disparities have been reported for sleep and cognitive health outcomes in later life, yet it is unknown whether sociodemographic disparities in sleep operate as mediators of sociodemographic disparities in cognitive aging. A deeper understanding of these associations is necessary to inform the development of tailored interventions aimed at reducing inequalities in cognitive aging.
This dissertation examined the associations between sleep and cognition among older adults and identified potential sociodemographic group differences in three separate studies. Study 1 examined the associations between distinct insomnia symptoms and subsequent cognitive performance across multiple domains in a longitudinal epidemiological sample, and additionally investigated whether insomnia—cognition associations are mediated through mental and physical health pathways and moderated by gender. Study 2 examined whether different patterns in the chronicity of difficulty initiating sleep are associated with subsequent cognitive functioning and decline in a nationally representative sample of older adults, and whether patterns of difficulty initiating sleep and associations between difficulty initiating sleep and cognition differ across four race-gender intersectional groups. Study 3 examined whether diagnosed sleep apnea and sleep apnea risk mediate racial disparities in cognition in a cross-sectional regional sample of Black and White older adults, and whether associations among race, sleep apnea, and cognition are conditional upon socioeconomic status.
Together, all three studies provide evidence for insomnia and sleep apnea as contributors to sociodemographic disparities in cognitive aging and suggest that these disparities may arise from both greater exposure to as well as differential impact of poor sleep health across gender, racial, and intersectional identities. The use of more comprehensive measures of sleep health across studies reveal that difficulty initiating sleep may be the insomnia phenotype most consequential for subsequent cognitive function, particularly when experienced intermittently, and that assessing sleep apnea diagnosis status does not accurately reflect disease presence in the community. Results also highlight the importance of intersectionality in health disparities, particularly with respect to the synergistic effects of racism and classism for health care access and health outcomes. Overall, findings from each of these studies offer several potential targets for interventions aimed at reducing inequalities in cognitive aging.PhDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/178155/1/afsaraz_1.pd
Dissociable Mesocorticolimbic Contributions to Pleasure and Motivation
No full textMesocorticolimbic systems are heavily implicated in the control of reward. Reward contains multiple components that include ‘liking’, ‘wanting’, and learning processes (Berridge, 2004; Berridge & Robinson, 2003; Morales & Berridge, 2020).Over many decades, most attention has been paid to understanding ‘wanting’ and learning components, and ‘liking’ has remained the least understood. However, recent progress in understanding brain generators of hedonic impact has been made through the identification of brain hedonic hotspots, or small subregions of mesocorticolimbic systems that causally amplify affective ‘liking’ expressions to pleasant tastes in nucleus accumbens medial shell (NAc), caudolateral ventral pallidum (VP), rostromedial orbitofrontal cortex (OFC), and caudal insula in response to a few neurochemical signals including orexin and mu-opioid receptor agonists (Castro et al., 2016; Castro & Berridge, 2014c, 2017; Ho & Berridge, 2013; Mahler et al., 2007; Peciña & Berridge, 2005; K. S. Smith & Berridge, 2005; Söderpalm & Berridge, 2000).
Thus far, hedonic hotspot sites within mesocorticolimbic regions have primarily been studied using drug microinjection techniques, such as through the use of mu-opioid, orexin, and endocannabinoid agonists. This leaves open the possibility that hedonic hotspot amplification of ‘liking’ reactions is a mere artifact of the pharmacological approaches used, rather than a true neurobiological mechanism that exerts hedonic control. In order to provide triangulating evidence that hedonic hotspots are true neurofunctional entities capable of controlling affective responses, I use optogenetic techniques as an alternative method of controlling neuronal activity within known hedonic hotspot sites in OFC and insula in Chapter 2. In Chapter 3 I investigate a region of mid cingulate cortex in rats that has never been previously tested for hedonic function. In Chapter 4, my efforts move subcortically to probe the necessity of the caudolateral ventral pallidum hedonic hotspot for normal ‘liking’. Finally, in Chapter 5 I investigate amygdala control of incentive motivation for intravenous opioids.
Altogether, this dissertation demonstrates that mesocorticolimbic systems in OFC, insula, cingulate cortex, ventral pallidum, and central amygdala are crucial sites for the control of ‘liking’ and/or ‘wanting’ for reward. Importantly however, ‘liking’ is restricted to small subregions of hedonic hotspots where optogenetic manipulations casually amplify hedonic impact for sweetness. Outside of these hotspots, optogenetic manipulations fail to increase ‘liking’ reactions, and sometimes even oppositely suppress affective reactions. In some cases, such in central amygdala, maladaptive ‘wanting’ can be generated for natural and drug rewards that is never matched in changes in ‘liking’. The neural mechanisms underlying these different motivational and hedonic processes provide important insights onto hedonic and motivational dysfunctions that may contribute to various affective and other psychological disorders.PhDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/194522/1/ileanamo_1.pd
Auditory Cortical Ensemble-Mechanisms Facilitating Auditory-Driven Behaviors and Perception
No full textSounds in our everyday environment play a crucial role in guiding our perception and behaviors. The ability to effectively process these sounds—perceive them, contextualize their meaning, and subsequently harness this information to adapt our behaviors—is an intricate yet fundamental process. Consider, for instance, the familiar experience of recognizing a friend's voice in a bustling crowd, or the moment when a sudden car horn prompts a swift response to ensure safety. These everyday scenarios underscore the significance of auditory perception, which is known to rely on the auditory cortex within the auditory system. The auditory cortex, a higher-level brain region in the auditory pathway, performs a multifaceted role in processing sounds, beyond the mere analysis of their acoustic features. It is essential for processing spectrotemporally rich sounds like human speech or animal vocalizations, which carry ethological relevance, and contributes to our ability to engage in sound-guided behavior and decision-making. However, how the auditory cortex brings together all the moving parts in our acoustic environment to facilitate a stable auditory perception across contextual variations and time, is still an enigma. This dissertation tackles this challenge by examining neural mechanisms in the auditory cortex at two distinct temporal scales, and its functioning under baseline conditions and in behavioral contexts, providing comprehensive insights into the functioning of the auditory cortex in real-world contexts.
The first study in this dissertation addresses the long-term stability of auditory cortical sound representations, comparing the processing of complex sounds like animal vocalizations, with that of simple sounds like pure tones. By recording the sound-evoked neural responses in the auditory cortex using two-photon calcium imaging, this study provides evidence for the distinction in longitudinal sound representations in the auditory cortex based on the acoustic structure and salience of the auditory inputs. The second study moves to investigate auditory cortical mechanisms in a behavioral context. In this study, I adapted the classical appetitive trace conditioning paradigm to train mice in predicting the time to reward, using a sound cue. By combining electrophysiology, chemogenetic and pharmacological interventions, this study establishes the causal and functional role of auditory cortex and its downstream connection to the posterior striatum in sound-triggered interval timekeeping, at a 1-second temporal resolution. Collectively, these studies offer insights about how neural representations in the auditory cortex can simultaneously encode for auditory and relevant non-auditory information like timing, which are necessary for shaping our consequent actions and behaviors. This work makes an essential contribution to the literature on the various auditory cortical mechanisms aiding in auditory perception but also underscores the importance of recognizing the auditory cortex as a region with broader functions beyond primary auditory processing.PhDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/193182/1/harinis_1.pd
- …
