Ⅱ. Summary of Special Lectures
Albert and Ellen Grass Lecture – Receptor, Neurons, and Circuits: The Biology of
Mammalian Taste by Dr. Charles Zuker
Ⅲ. Summary of Nanosymposium
B) Neural Excitability, Synapses, and Glia: Cellular Mechanisms
C) Disorders of Nervous System
D) Sensory and Motor Systems
E) Integrative Systems: Neuroendocrinology, Neuroimmunology, and Homeostatic Challenge
Ⅳ. Association of Korean Neuroscientists: Annual Meeting and Social
Ⅴ. Closing Remarks
View of downtown Chicago (Left); A flyer that held in front of the McCormick Place (Right).
The 45th Annual Neuroscience meeting was taken place in Chicago, IL. More than 29,000 people attended this year’s meeting. The meeting was divided into 8 themes (A) Development, (B) Neural Excitability, Synapses, and Glia: Cellular Mechanisms, (C) Disorders of Nervous System, (D) Sensory and Motor Systems, (E) Integrative Systems: Neuroendocrinology, Neuroimmunology, and Hoemostatic Challenge, (F) Cognition and Behavior, (G) Novel Methods and technology Development, and (H) History, Teaching, Public Awareness, and Societal Impacts in Neuroscience, in which I’ll be focusing the first 5 themes in this review.
Each theme was accompanied by at least one special lecture, symposiums, mini-symposiums, nano-symposiums, and poster sessions. Each day, there were at least 3 special lectures, two poster sessions held in the morning (8 a.m. – 12 p.m.) and in the afternoon (1 p.m. – 5 p.m.), followed by satellite meetings/socials in the evening. Overall, one had to curate itineraries really well to get the most out of the annual meeting.
Lecture on “Development and Reprogramming of Neuronal Diversity in the Central Nervous System” by Dr. Paolo Arlotta from Harvard University.
Ⅱ. Special Lecture:
Receptor, Neuron, and Circuits: The Biology of Mammalian Taste by Dr. Charles Zuker
Dr. Zuker’s lab from Columbia University studies mammalian taste neurons that interact with specific receptors that are responsible for detecting and responding to sweet, bitter, umami, salty and sour stimuli. These stimuli lead to a circuit involving the amygdala, hypothalamus, entorthinal cortex and other brain structures. Each taste is sensed by a unique set of neurons and these are arranged discretely in “gustotopic map.” Dr. Zuker’s lab demonstrates that, by manipulation specific neurons or the corresponding receptors, one manipulate rodent’s perception of taste of something bitter as delightfully sweet. The bigger logic is not limited to how we perceive these tastes; moreover, his findings, “tasting coding,” is a model system to study how our brain signal outside stimuli and how those stimuli transforms sensory signals at the periphery into perception and change the behaviors.
Ⅲ. Summary of Symposium or Nanosymposim
Postnatal neurogenesis is a topic that actively studied for past 30 years. Neurogenesis, a process of generating new neurons, mainly observed in two regions of brain: sub-ventricle zone (SVZ) of olfactory bulb, and sub-granular zone (SGZ) of hippocampus (Ming and Song, 2011). Importantly, SGZ of hippocampus has demonstrated to play an important role in de-/formation of new memory and perception.
Dr. F. Gage group from Salk Institute, showed that c-myc couples proliferation to differentiation in adult neurogenesis. C-myc is part of Wnt pathway target and play important role in cell growth, proliferation, apoptosis and differentiation. They used retroviral expression of c-myc in the dentate gyrus (DG) of SGZ and observed increase in proliferation and subsequent inhibition of differentiation in dose-dependent manner.
Dr. C. Grassi group from University of Cattolica, investigated CREB-Sirt1-Hes1 circuitry in neural stem cell responses upon glucose availability. They observed that NSC cultured in high glucose level resulted in reduced proliferation and self-renewal capacity compared to NSC cultured in normal (physiological) level. They found that low glucose availability promoted CREB binding to the CRE surrounding chromatin and increased histone H3 acetylation and regulate Hes1 expression via Sirt1.
Dr. M. H. Jang group from Mayo Clinic, investigated the role of BubR1 (mitotic checkpoint protein) in brain aging. They observed that BubR1 is widely expressed in the hippocampus and the expression level reduces upon aging. BubR1 insufficiency impaired neural progenitor proliferation, maturation and dendrite development. These mice showed increased anxiety and impaired memory function.
B) Neural Excitability, Synapses, and Glia: Cellular Mechanisms
“Dysregulation of Mammalian Target of Rapamycin Signaling in Mouse Model of Autism”
Autism is a disorder characterized by anti-social, anti-communicative and repetitive behaviors. Although the exact cause and genetic implication is remains controversial, we now know that over-activation of mTOR signaling is a major player in impaired synaptic plasticity, neural networks and behaviors in autism spectrum disorder (Subramanian et al., 2015).
Dr. R. Zukin group at Albert Einstein, utilized Nse-Cre Pten conditional knockout mice which result in ablation of PTEN in granule cells of the dentate gyrus and pyramidal neurons but not CA1 lead to autism-like phenotype, including deficit in social and cognitive behavior. They observed two phosphatidylinositol 3-kinase- and protein synthesis-dependent forms of synaptic plasticity, theta burst-induced long-term potentiation and metabotropic glutamate receptor (mGluR)-dependent long-term depression are dysregulated; however, long-term potentiation and mGluR-dependent long-term depression are normal at CA3-CA1 pyramidal cell synapse.
Dr. E. Klann group at New York University, investigated the effect of altered hyper translational control resulting in exaggerated protein synthesis in autism. They observed that mice with genetically upregulated translation initiation factor 4E (EIF4E), which is reported to be associated with autism, result in exaggerated cap-dependent translation and aberrant behavior such as repetitive and perseverative behavior and social interaction deficit. These mice also showed synaptic pathophysiology in medial prefrontal cortex, striatum and hippocampus.
C) Disorders of Nervous System
“Alzheimer’s Disease-Experimental Therapeutics”
Based on reports from Alzheimer’s Association, nearly 44 millions people have Alzheimer’s related dementia worldwide. However, there are no treatment that prevent, cure, or delay the disease, underlining the need for novel therapeutics.
Dr. Francis group from Rowan-SOM showed a novel metabolic gene therapy-based strategy for the treatment of Alzheimer’s disease. They manifested abnormalities in the metabolism of the abundant amino acid derivative N-acetyl-L-aspartic acid (NAA) in 5xFAD mouse model of AD. They observed significant downregulation of genes that encode for NAA synthase in the hippocampus, thalamus, and cortex. They showed that viral vector-mediated expression of NAA-deacetylation in forebrain neurons of 5xFAD mice result in improved energetic status, reduced amyloid burden, and promote cell survival which also showed improvement in the long-term spatial memory function.
Dr. Madison group from University Wisconsin, Madison, showed metabotropic glutamate receptor 5 (mGluR5) is a potential therapeutic target for Alzheimer’s disease. Many mGluR5 antagonists such as fenobam and CTEP have been clinically proven to reduce pathogenesis of Parkinson’s diseases, epilepsy and fragile X syndrome. Previously they identified amyloid beta protein precursor mRNA (App) as a synaptic target via mGluR5 signaling. They found that these mGluR5 antagonists as a viable therapeutic strategy to reduce amyloid beta plague and rescue learning and memory deficit in the AD mouse model.
Dr. Bhaskar group from University of New Mexico investigated a novel virus-like particles (VLPs) based vaccine against tau pathology. They engineered VLP-immunogen by conjugating a pathologically relevant form of tau peptide onto Q-beta-BLP particle. They immunized intramuscularly, bi-weekly for 60weeks to rTg-4510, a mouse model of tau-pathology. They observed 5-fold increase of antibody titers against the specific pTau protein in the immunized mice but not in control (non-conjugated immunogen). The immunized mice also resulted in significant improvement in learning/memory based behavior tests, such as novel object recognition and the Morris water maze test.
D) Sensory and Motor Systems: Auditory System:
“Sensory Transduction and Hair Cell Differentiation”
In mammals, cochlear sensory hair cells, which are responsible for hearing, are postmitotic and cannot be replaced after loss (Atkinson et al., 2015). One of the method to regenerate the lost hair cell is through trans-differentiation of surrounding supporting cells to hair cells.
Dr. Defourny group from University of Liege showed that hair cell can be directly generated from supporting cells by inhibition of ephrin-B2 signaling. Using either ephrin-B2 conditional knockout mice, shRNA-mediated gene silencing or soluble inhibitors, they found that down-regulation of ephrin-B2 signaling at embryonic stages result in support cell translocation into hair cell layer and subsequent switch in cell identity into hair cell.
Dr. Holt group from Harvard medical school, investigated Tmc1 mutagenesis in a mouse inner ear hair cell. Transmembrane channel-like 1 and 2 (TMC1 and TMC2) has been associated with hair cell sensory transduction channel. When they transfected a vector containing cysteine substituted Tmc1 sequence into organotypic culture harvested from Tmc1/Tmc2 double-knockout mice, they found that mutant Tmc1 sequences restored mechanosensitivity and that acute application of cysteine modification reagent irreversibly these effects. The data support a direct role for TMC1 in sensory transduction in mammalian hair cells and cysteine may play an important role in mechanosensitivity.
E) Integrative Systems: Neuroendocrinology, Neuroimmunology, and Hoemostatic Challenge
“Circadian Entrainment Mechanisms and Consequences”
Circadian rhythms are ~24h oscillations, which are internally generated and function to anticipate the environmental changes associated with the solar day (Videnovic et al., 2014).
Dr. McMahon group from University of Alabama at Brimingham, investigated whether changes in hippocampal formation, such as gene expression, long-term potentiation, and learning and memory, are regulated by the circadian molecular clock. They observed that GSK3β exhibit 24h-rhythm in CA1 regions. They utilized pharmacological GSK3 inhibitor and observed reduction in LTP magnitude during the night, and facilitated spontaneous alternation performance (method to measure short-term memory) during the day. They concluded that GSK3 regulates the molecular clock and day/night differences in synaptic plasticity and memory.
Ⅳ. Association of Korean Neuroscientists (AKN): Annual Meeting and Social
AKN annual meeting was held at Congress Plaza Hotel on October 19, 2015. There were approximately 230 attendees. The annual meeting was accompanied by dinner then introductory special lectures by KBRI, KIST, and IBS. To my surprise, AKN was also giving out awards for Pre-doctoral, Post-doctoral and Junior Faculty Award. This year’s Junior Faculty Award was given to Dr. Hunsoo Shawn Je from Duke-NUS, Dr. Jungsu Kim from Mayo Clinic and Dr. Hanseok Ko from Johns Hopkins University.
AKN annual meeting held at Congress Plaza Hotel (Photo was taken from AKN website / summary report)
Ⅴ. Closing Remarks
As SfN is one of the biggest international neuroscience conference, it was such a great experience to be part of the conference and meet people to share each other’s research. It was also very pleasing to learn about AKN and their efforts to bring all Korean neuroscientists together and have a networking session. Next Neuroscience meeting (2016) will be held at San Diego, California.
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