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Frontiers in Behavioral Neuroscience 2022Learning to identify and predict threats is a basic skill that allows animals to avoid harm. Studies in invertebrates like , and have revealed that the basic mechanisms... (Review)
Review
Learning to identify and predict threats is a basic skill that allows animals to avoid harm. Studies in invertebrates like , and have revealed that the basic mechanisms of learning and memory are conserved. We will summarize these studies and highlight the common pathways and mechanisms in invertebrate fear-associated behavioral changes. Fear conditioning studies utilizing electric shock in and have demonstrated that serotonin or dopamine are typically involved in relaying aversive stimuli, leading to changes in intracellular calcium levels and increased presynaptic neurotransmitter release and short-term changes in behavior. Long-term changes in behavior typically require multiple, spaced trials, and involve changes in gene expression. studies have demonstrated these basic aversive learning principles as well; however, fear conditioning has yet to be explicitly demonstrated in this model due to stimulus choice. Because predator-prey relationships can be used to study learned fear in a naturalistic context, this review also summarizes what is known about predator-induced behaviors in these three organisms, and their potential applications for future investigations into fear conditioning.
PubMed: 36439964
DOI: 10.3389/fnbeh.2022.1008818 -
The Journal of Experimental Biology Jun 2018Sleep is nearly ubiquitous throughout the animal kingdom, yet little is known about how ecological factors or perturbations to the environment shape the duration and... (Review)
Review
Sleep is nearly ubiquitous throughout the animal kingdom, yet little is known about how ecological factors or perturbations to the environment shape the duration and timing of sleep. In diverse animal taxa, poor sleep negatively impacts development, cognitive abilities and longevity. In addition to mammals, sleep has been characterized in genetic model organisms, ranging from the nematode worm to zebrafish, and, more recently, in emergent models with simplified nervous systems such as and jellyfish. In addition, evolutionary models ranging from fruit flies to cavefish have leveraged natural genetic variation to investigate the relationship between ecology and sleep. Here, we describe the contributions of classical and emergent genetic model systems to investigate mechanisms underlying sleep regulation. These studies highlight fundamental interactions between sleep and sensory processing, as well as a remarkable plasticity of sleep in response to environmental changes. Understanding how sleep varies throughout the animal kingdom will provide critical insight into fundamental functions and conserved genetic mechanisms underlying sleep regulation. Furthermore, identification of naturally occurring genetic variation regulating sleep may provide novel drug targets and approaches to treat sleep-related diseases.
Topics: Biological Evolution; Models, Animal; Sleep
PubMed: 29895581
DOI: 10.1242/jeb.159533 -
Cold Spring Harbor Perspectives in... Dec 2019When protein/peptides aggregate, they usually form the amyloid state consisting of cross β-sheet structure built by repetitively stacked β-strands forming long... (Review)
Review
When protein/peptides aggregate, they usually form the amyloid state consisting of cross β-sheet structure built by repetitively stacked β-strands forming long fibrils. Amyloids are usually associated with disease including Alzheimer's. However, amyloid has many useful features. It efficiently transforms protein from the soluble to the insoluble state in an essentially two-state process, while its repetitive structure provides high stability and a robust prion-like replication mechanism. Accordingly, amyloid is used by nature in multifaceted and ingenious ways of life, ranging from bacteria and fungi to mammals. These include (1) Structure: Templating for small chemical molecules (Pmel17), biofilm formation in bacteria (curli), assisting aerial hyphae formation in streptomycetes (chaplins) or monolayer formation at a surface (hydrophobins). (2) Reservoirs: A storage state for peptide/proteins to protect them from their surroundings or vice versa (storage of peptide hormones in mammalian secretory granules or major basic protein in eosinophils). (3) Information carriers: The fungal immune system (HET-s prion in , yeast prions) or long-term memory (e.g., mnemons in yeast, cytoplasmic polyadenylation element-binding protein in aplysia). Aggregation is also used to (4) "suppress" the function of the soluble protein (e.g., Cdc19 in yeast stress granules), or (5) "signaling" through formation of oligomers (e.g., HET-s prion, necroptosis-related proteins RIP1/RIP3). This review summarizes current knowledge on functional amyloids with a focus on the amyloid systems curli in bacteria, HET-s prion in , and peptide hormone storage in mammals together with an attempt to highlight differences between functional and disease-associated amyloids.
Topics: Amyloid; Bacteria; Fungi; Structure-Activity Relationship
PubMed: 31088827
DOI: 10.1101/cshperspect.a033860 -
Cold Spring Harbor Perspectives in... Feb 2015The simplicity and tractability of the neural circuits mediating behaviors in invertebrates have facilitated the cellular/molecular dissection of neural mechanisms... (Review)
Review
The simplicity and tractability of the neural circuits mediating behaviors in invertebrates have facilitated the cellular/molecular dissection of neural mechanisms underlying learning. The review has a particular focus on the general principles that have emerged from analyses of an example of nonassociative learning, sensitization in the marine mollusk Aplysia. Learning and memory rely on multiple mechanisms of plasticity at multiple sites of the neuronal circuits, with the relative contribution to memory of the different sites varying as a function of the extent of training and time after training. The same intracellular signaling cascades that induce short-term modifications in synaptic transmission can also be used to induce long-term changes. Although short-term memory relies on covalent modifications of preexisting proteins, long-term memory also requires regulated gene transcription and translation. Maintenance of long-term cellular memory involves both intracellular and extracellular feedback loops, which sustain the regulation of gene expression and the modification of targeted molecules.
Topics: Animals; Invertebrates; Learning
PubMed: 25722464
DOI: 10.1101/cshperspect.a021675 -
JACC. Cardiovascular Interventions Dec 2021
Topics: Heart Ventricles; Humans; Shock, Cardiogenic; Treatment Outcome
PubMed: 34949395
DOI: 10.1016/j.jcin.2021.10.012 -
Trends in Neurosciences Mar 2023Chronic pain caused by injury or disease of the nervous system (neuropathic pain) has been linked to persistent electrical hyperactivity of the sensory neurons... (Review)
Review
Chronic pain caused by injury or disease of the nervous system (neuropathic pain) has been linked to persistent electrical hyperactivity of the sensory neurons (nociceptors) specialized to detect damaging stimuli and/or inflammation. This pain and hyperactivity are considered maladaptive because both can persist long after injured tissues have healed and inflammation has resolved. While the assumption of maladaptiveness is appropriate in many diseases, accumulating evidence from diverse species, including humans, challenges the assumption that neuropathic pain and persistent nociceptor hyperactivity are always maladaptive. We review studies indicating that persistent nociceptor hyperactivity has undergone evolutionary selection in widespread, albeit selected, animal groups as a physiological response that can increase survival long after bodily injury, using both highly conserved and divergent underlying mechanisms.
Topics: Humans; Animals; Nociceptors; Sensory Receptor Cells; Neuralgia; Adaptation, Physiological
PubMed: 36610893
DOI: 10.1016/j.tins.2022.12.007 -
Cold Spring Harbor Perspectives in... Apr 2015This work reviews research on neural mechanisms of two types of associative learning in the marine mollusk Aplysia, classical conditioning of the gill- and... (Review)
Review
This work reviews research on neural mechanisms of two types of associative learning in the marine mollusk Aplysia, classical conditioning of the gill- and siphon-withdrawal reflex and operant conditioning of feeding behavior. Basic classical conditioning is caused in part by activity-dependent facilitation at sensory neuron-motor neuron (SN-MN) synapses and involves a hybrid combination of activity-dependent presynaptic facilitation and Hebbian potentiation, which are coordinated by trans-synaptic signaling. Classical conditioning also shows several higher-order features, which might be explained by the known circuit connections in Aplysia. Operant conditioning is caused in part by a different type of mechanism, an intrinsic increase in excitability of an identified neuron in the central pattern generator (CPG) for feeding. However, for both classical and operant conditioning, adenylyl cyclase is a molecular site of convergence of the two signals that are associated. Learning in other invertebrate preparations also involves many of the same mechanisms, which may contribute to learning in vertebrates as well.
Topics: Animals; Invertebrates; Learning
PubMed: 25877219
DOI: 10.1101/cshperspect.a021709 -
Cold Spring Harbor Perspectives in... Jan 2017Prions are proteins that can adopt self-perpetuating conformations and are traditionally regarded as etiological agents of infectious neurodegenerative diseases in... (Review)
Review
Prions are proteins that can adopt self-perpetuating conformations and are traditionally regarded as etiological agents of infectious neurodegenerative diseases in humans, such as Creutzfeldt-Jakob disease, kuru, and transmissible encephalopathies. More recently, a growing consensus has emerged that prion-like, self-templating mechanisms also underlie a variety of neurodegenerative disorders, including amyotrophic lateral sclerosis, Alzheimer's disease, and Huntington's disease. Perhaps most surprising, not all prion-like aggregates are associated with pathological changes. There are now several examples of prion-like proteins in mammals that serve positive biological functions in their aggregated state. In this review, we discuss functional prions in the nervous system, with particular emphasis on the cytoplasmic polyadenylation element-binding protein (CPEB) and the role of its prion-like aggregates in synaptic plasticity and memory. We also mention a more recent example of a functional prion-like protein in the brain, TIA-1, and its role during stress. These studies of functional prion-like proteins have provided a number of generalizable insights on how prion-based protein switches may operate to serve physiological functions in higher eukaryotes.
Topics: Animals; Aplysia; Brain; Drosophila; Humans; Memory; Models, Animal; Prions; Serotonin; Synapses; Transcription Factors; mRNA Cleavage and Polyadenylation Factors
PubMed: 28049644
DOI: 10.1101/cshperspect.a023671 -
Neuropharmacology Nov 2021Glutamate (Glu) is the primary excitatory transmitter in the mammalian brain. But, we know little about the evolutionary history of this adaptation, including the... (Review)
Review
Glutamate (Glu) is the primary excitatory transmitter in the mammalian brain. But, we know little about the evolutionary history of this adaptation, including the selection of l-glutamate as a signaling molecule in the first place. Here, we used comparative metabolomics and genomic data to reconstruct the genealogy of glutamatergic signaling. The origin of Glu-mediated communications might be traced to primordial nitrogen and carbon metabolic pathways. The versatile chemistry of L-Glu placed this molecule at the crossroad of cellular biochemistry as one of the most abundant metabolites. From there, innovations multiplied. Many stress factors or injuries could increase extracellular glutamate concentration, which led to the development of modular molecular systems for its rapid sensing in bacteria and archaea. More than 20 evolutionarily distinct families of ionotropic glutamate receptors (iGluRs) have been identified in eukaryotes. The domain compositions of iGluRs correlate with the origins of multicellularity in eukaryotes. Although L-Glu was recruited as a neuro-muscular transmitter in the early-branching metazoans, it was predominantly a non-neuronal messenger, with a possibility that glutamatergic synapses evolved more than once. Furthermore, the molecular secretory complexity of glutamatergic synapses in invertebrates (e.g., Aplysia) can exceed their vertebrate counterparts. Comparative genomics also revealed 15+ subfamilies of iGluRs across Metazoa. However, most of this ancestral diversity had been lost in the vertebrate lineage, preserving AMPA, Kainate, Delta, and NMDA receptors. The widespread expansion of glutamate synapses in the cortical areas might be associated with the enhanced metabolic demands of the complex brain and compartmentalization of Glu signaling within modular neuronal ensembles.
Topics: Animals; Biological Evolution; Glutamic Acid; Receptors, Glutamate; Signal Transduction; Synapses
PubMed: 34343611
DOI: 10.1016/j.neuropharm.2021.108740 -
Handbook of Clinical Neurology 2019Chronic pain is a frequent condition that affects an estimated 20% of people worldwide, accounting for 15%-20% of doctors' appointments (Treede et al., 2015). It lacks... (Review)
Review
Chronic pain is a frequent condition that affects an estimated 20% of people worldwide, accounting for 15%-20% of doctors' appointments (Treede et al., 2015). It lacks the acute warning function of physiologic nociception, and instead involves the activation of multiple neurophysiologic mechanisms in the somatosensory system, a complex neuronal network under the control of powerful autoregulatory loops and able to undergo rapid neuroplastic alteration (Verdu et al., 2008). There is a growing body of research suggesting that some such pathways are shared by major psychologic disorders such as depression and anxiety, opening new avenues in co-treatment strategies. In particular, besides anticonvulsants, which are today used as analgesics, other psychopharmaceuticals, such as the tricyclic antidepressants, are displaying efficacy in the treatment of neuropathic and nociceptive chronic pain. The state of the art regarding the mechanisms of nociception and the pharmacology of both the neurotransmitters involved and the wide range of psychoactive compounds that may be useful in the treatment of chronic pain are discussed.
Topics: Analgesics; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Chronic Pain; Humans; Psychopharmacology
PubMed: 31727220
DOI: 10.1016/B978-0-444-64012-3.00019-8