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Associative learning genetic circuits

Annekathrin Widmann, Marc Artinger, Lukas Biesinger, Kathrin Boepple, Christina Peters, Jana Schlechter, Mareike Selcho, Andreas S Thum
Memory formation is a highly complex and dynamic process. It consists of different phases, which depend on various neuronal and molecular mechanisms. In adult Drosophila it was shown that memory formation after aversive Pavlovian conditioning includes-besides other forms-a labile short-term component that consolidates within hours to a longer-lasting memory. Accordingly, memory formation requires the timely controlled action of different neuronal circuits, neurotransmitters, neuromodulators and molecules that were initially identified by classical forward genetic approaches...
October 2016: PLoS Genetics
Wei-Hsiang Huang, Casey J Guenthner, Jin Xu, Tiffany Nguyen, Lindsay A Schwarz, Alex W Wilkinson, Or Gozani, Howard Y Chang, Mehrdad Shamloo, Liqun Luo
Haploinsufficiency of Retinoic Acid Induced 1 (RAI1) causes Smith-Magenis syndrome (SMS), which is associated with diverse neurodevelopmental and behavioral symptoms as well as obesity. RAI1 encodes a nuclear protein but little is known about its molecular function or the cell types responsible for SMS symptoms. Using genetically engineered mice, we found that Rai1 preferentially occupies DNA regions near active promoters and promotes the expression of a group of genes involved in circuit assembly and neuronal communication...
September 22, 2016: Neuron
Longwen Huang, Kevin Ung, Isabella Garcia, Kathleen B Quast, Keith Cordiner, Peter Saggau, Benjamin R Arenkiel
UNLABELLED: Elucidating patterns of functional synaptic connectivity and deciphering mechanisms of how plasticity influences such connectivity is essential toward understanding brain function. In the mouse olfactory bulb (OB), principal neurons (mitral/tufted cells) make reciprocal connections with local inhibitory interneurons, including granule cells (GCs) and external plexiform layer (EPL) interneurons. Our current understanding of the functional connectivity between these cell types, as well as their experience-dependent plasticity, remains incomplete...
August 24, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Isabelle A Spühler, Gaurasundar M Conley, Frank Scheffold, Simon G Sprecher
Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster...
2016: Frontiers in Cellular Neuroscience
Xiaoming Wang, Alexandra L Bey, Brittany M Katz, Alexandra Badea, Namsoo Kim, Lisa K David, Lara J Duffney, Sunil Kumar, Stephen D Mague, Samuel W Hulbert, Nisha Dutta, Volodya Hayrapetyan, Chunxiu Yu, Erin Gaidis, Shengli Zhao, Jin-Dong Ding, Qiong Xu, Leeyup Chung, Ramona M Rodriguiz, Fan Wang, Richard J Weinberg, William C Wetsel, Kafui Dzirasa, Henry Yin, Yong-Hui Jiang
Human neuroimaging studies suggest that aberrant neural connectivity underlies behavioural deficits in autism spectrum disorders (ASDs), but the molecular and neural circuit mechanisms underlying ASDs remain elusive. Here, we describe a complete knockout mouse model of the autism-associated Shank3 gene, with a deletion of exons 4-22 (Δe4-22). Both mGluR5-Homer scaffolds and mGluR5-mediated signalling are selectively altered in striatal neurons. These changes are associated with perturbed function at striatal synapses, abnormal brain morphology, aberrant structural connectivity and ASD-like behaviour...
2016: Nature Communications
Francesco Papaleo, Feng Yang, Clare Paterson, Sara Palumbo, Gregory V Carr, Yanhong Wang, Kirsten Floyd, Wenwei Huang, Craig J Thomas, Jingshan Chen, Daniel R Weinberger, Amanda J Law
UNLABELLED: Schizophrenia is a chronic, disabling neuropsychiatric disorder with complex genetic origins. The development of strategies for genome manipulation in rodents provides a platform for understanding the pathogenic role of genes and for testing novel therapeutic agents. Neuregulin 1 (NRG1), a critical developmental neurotrophin, is associated with schizophrenia. The NRG1 gene undergoes extensive alternative splicing and, to date, little is known about the neurobiology of a novel NRG1 isoform, NRG1-IV, which is increased in the brains of individuals with schizophrenia and associated with genetic risk variation...
April 27, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Xiaojie Liu, Yao Chen, Jiaqing Tong, Ashley M Reynolds, Sarah C Proudfoot, Jinshun Qi, Peter Penzes, Youming Lu, Qing-Song Liu
UNLABELLED: Exchange protein directly activated by cAMP (Epac) and protein kinase A (PKA) are intracellular receptors for cAMP. Although PKA and its downstream effectors have been studied extensively in the context of drug addiction, whether and how Epac regulates cellular and behavioral effects of drugs of abuse remain essentially unknown. Epac is known to regulate AMPA receptor (AMPAR) trafficking. Previous studies have shown that a single cocaine exposure in vivo leads to an increase in GluA2-lacking AMPARs in dopamine neurons of the ventral tegmental area (VTA)...
April 27, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Lauren A M Lebois, Jonathan D Wolff, Kerry J Ressler
Neuroimaging genetic studies that associate genetic and epigenetic variation with neural activity or structure provide an opportunity to link genes to psychiatric disorders, often before psychopathology is discernable in behavior. Here we review neuroimaging genetics studies with participants who have Posttraumatic Stress Disorder (PTSD). Results show that genes related to the physiological stress response (e.g., glucocorticoid receptor and activity, neuroendocrine release), learning and memory (e.g., plasticity), mood, and pain perception are tied to neural intermediate phenotypes associated with PTSD...
April 21, 2016: Experimental Neurology
Philip Lieberman
Language primarily evolved as a vocal medium that transmits the attributes of human culture and the necessities of daily communication. Human language has a long, complex evolutionary history. Language also serves as an instrument of thought since it has become evident that in the course of this process neural circuits that initially evolved to regulate motor control, motor responses to external events, and ultimately talking were recycled to serve tasks such as working memory, cognitive flexibility linguistic tasks such as comprehending distinctions in meaning conveyed by syntax...
June 20, 2016: Journal of Anthropological Sciences, Rivista di Antropologia: JASS
Jeffrey P Rasmussen, Alvaro Sagasti
Damage to the central nervous system (CNS) of fish can often be repaired to restore function, but in mammals recovery from CNS injuries usually fails due to a lack of axon regeneration. The relatively growth-permissive environment of the fish CNS may reflect both the absence of axon inhibitors found in the mammalian CNS and the presence of pro-regenerative environmental factors. Despite their different capacities for axon regeneration, many of the physiological processes, intrinsic molecular pathways, and cellular behaviors that control an axon's ability to regrow are conserved between fish and mammals...
February 29, 2016: Experimental Neurology
Marc V Fuccillo
Autism spectrum disorders (ASD) are characterized by two seemingly unrelated symptom domains-deficits in social interactions and restrictive, repetitive patterns of behavioral output. Whether the diverse nature of ASD symptomatology represents distributed dysfunction of brain networks or abnormalities within specific neural circuits is unclear. Striatal dysfunction is postulated to underlie the repetitive motor behaviors seen in ASD, and neurological and brain-imaging studies have supported this assumption...
2016: Frontiers in Neuroscience
Ling-Bo Li, Haoyun Lei, Rachel N Arey, Pengpeng Li, Jianfeng Liu, Coleen T Murphy, X Z Shawn Xu, Kang Shen
Aging is the greatest risk factor for a number of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Furthermore, normal aging is associated with a decline in sensory, motor, and cognitive functions. Emerging evidence suggests that synapse alterations, rather than neuronal cell death, are the causes of neuronal dysfunctions in normal aging and in early stages of neurodegenerative diseases. However, little is known about the mechanisms underlying age-related synaptic decline. Here, we uncover a surprising role of the anterograde molecular motor UNC-104/KIF1A as a key regulator of neural circuit deterioration in aging C...
March 7, 2016: Current Biology: CB
J David Sweatt
This brief review summarizes sixty years of conceptual advances that have demonstrated a role for active changes in neuronal connectivity as a controller of behavior and behavioral change. Seminal studies in the first phase of the six-decade span of this review firmly established the cellular basis of behavior - a concept that we take for granted now, but which was an open question at the time. Hebbian plasticity, including LTP and LTD, was then discovered as being important for local circuit refinement in the context of memory formation and behavioral change and stabilization in the mammalian central nervous system...
February 14, 2016: Journal of Neurochemistry
Gemma Flore, Giuseppina Di Ruberto, Joséphine Parisot, Sara Sannino, Fabio Russo, Elizabeth A Illingworth, Michèle Studer, Elvira De Leonibus
The hippocampus (HP), a medial cortical structure, is subdivided into a distinct dorsal (septal) and ventral (temporal) portion, which is separated by an intermediate region lying on a longitudinal curvature. While the dorsal portion is more dedicated to spatial navigation and memory, the most ventral part processes emotional information. Genetic factors expressed in gradient during development seem to control the size and correct positioning of the HP along its longitudinal axis; however, their roles in regulating differential growth and in supporting its anatomical and functional dissociation remain unexplored...
January 26, 2016: Cerebral Cortex
Jan Gründemann, Andreas Lüthi
Associative fear learning in the basolateral amygdala (BLA) is crucial for an animal's survival upon environmental threats. BLA neurons are defined on the basis of their projection target, genetic markers, and associated function. BLA principal neuron responses to threat signaling stimuli are potentiated upon associative fear learning, which is tightly controlled by defined interneuron subpopulations. In addition, BLA population activity correlates with behavioral states and threat or safety signals. BLA neuronal ensembles activated by different behavioral signals can be identified using immediate early gene markers...
December 2015: Current Opinion in Neurobiology
Andrew C Giles, Karla J Opperman, Catharine H Rankin, Brock Grill
The PAM/Highwire/RPM-1 (PHR) proteins are signaling hubs that function as important regulators of neural development. Loss of function in Caenorhabditis elegans rpm-1 and Drosophila Highwire results in failed axon termination, inappropriate axon targeting, and abnormal synapse formation. Despite broad expression in the nervous system and relatively dramatic defects in synapse formation and axon development, very mild abnormalities in behavior have been found in animals lacking PHR protein function. Therefore, we hypothesized that large defects in behavior might only be detected in scenarios in which evoked, prolonged circuit function is required, or in which behavioral plasticity occurs...
October 13, 2015: G3: Genes—Genomes—Genetics
Astrid Rohwedder, Mareike Selcho, Bérénice Chassot, Andreas S Thum
All organisms continuously have to adapt their behavior according to changes in the environment in order to survive. Experience-driven changes in behavior are usually mediated and maintained by modifications in signaling within defined brain circuits. Given the simplicity of the larval brain of Drosophila and its experimental accessibility on the genetic and behavioral level, we analyzed if Drosophila neuropeptide F (dNPF) neurons are involved in classical olfactory conditioning. dNPF is an ortholog of the mammalian neuropeptide Y, a highly conserved neuromodulator that stimulates food-seeking behavior...
December 15, 2015: Journal of Comparative Neurology
Tomer Langberg, Ryan Dashek, Bernard Mulvey, Kimberly A Miller, Susan Osting, Carl E Stafstrom, Thomas P Sutula
Kindling is a phenomenon of activity-dependent neural circuit plasticity induced by repeated seizures that results in progressive permanent increases in susceptibility to epilepsy. As the permanent structural and functional modifications induced by kindling include a diverse range of molecular, cellular, and functional alterations in neural circuits, it is of interest to determine if genetic background associated with seizure-induced plasticity might also influence plasticity in neural circuitry underlying other behaviors...
January 2016: Neurobiology of Disease
Maria Lobikin, Daniel Lobo, Douglas J Blackiston, Christopher J Martyniuk, Elizabeth Tkachenko, Michael Levin
Experimentally induced depolarization of resting membrane potential in "instructor cells" in Xenopus laevis embryos causes hyperpigmentation in an all-or-none fashion in some tadpoles due to excess proliferation and migration of melanocytes. We showed that this stochastic process involved serotonin signaling, adenosine 3',5'-monophosphate (cAMP), and the transcription factors cAMP response element-binding protein (CREB), Sox10, and Slug. Transcriptional microarray analysis of embryos taken at stage 15 (early neurula) and stage 45 (free-swimming tadpole) revealed changes in the abundance of 45 and 517 transcripts, respectively, between control embryos and embryos exposed to the instructor cell-depolarizing agent ivermectin...
October 6, 2015: Science Signaling
Wan-Chun Liu, Jessica Kohn, Sarah K Szwed, Eben Pariser, Sharon Sepe, Bhagwattie Haripal, Naoki Oshimori, Martin Marsala, Atsushi Miyanohara, Ramee Lee
Speech and vocal impairments characterize many neurological disorders. However, the neurogenetic mechanisms of these disorders are not well understood, and current animal models do not have the necessary circuitry to recapitulate vocal learning deficits. We developed germline transgenic songbirds, zebra finches (Taneiopygia guttata) expressing human mutant huntingtin (mHTT), a protein responsible for the progressive deterioration of motor and cognitive function in Huntington's disease (HD). Although generally healthy, the mutant songbirds had severe vocal disorders, including poor vocal imitation, stuttering, and progressive syntax and syllable degradation...
November 2015: Nature Neuroscience
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