Molecular and Cellular Neuroscience Program Brain and Cognitive Sciences

Similarly, understanding the local brainstem networks that underlie the generation and regulation of breathing is a necessary step to understanding the mechanisms of SIDS (Sudden Infant Death Syndrome). Finally, we are interested in KlAnnLabNyu.org the identification of the role of unipolar brush cells, a recently discovered cell type of the cerebellar cortex, in cerebellar microcircuits. In the mid to late 1970s, George Stefano first approached me with the suggestion that we start a new scientific journal. The initial suggestion was that the subject matter be limited to invertebrate neurobiology. George and his group were involved in finding opiate receptors in the invertebrate nervous system. At the time, my major research was study of neurotransmitter and peptide receptors on Aplysia neurons.

Neuronal gene expression

Current projects are investigating altered synaptic signaling in mouse models of obsessive compulsive disorder, schizophrenia and fragile X syndrome. Johns Hopkins researchers collaborate extensively with researchers from multiple disciplines to bring together expertise in the areas of molecular biology, genetics, biochemistry, cell biology, anatomy, cellular electrophysiology, and imaging. Utilizing cellular and molecular tools, research into the development and function of the nervous system addresses fundamental questions that relate to high-level neuronal function. By looking at diverse biological mechanisms such as sensation, biological rhythms, emotion, and memory and cognition as well as genetic and acquired diseases, researchers have made discoveries with wide-ranging implications. Early studies into the neuromodulatory information encoded by midbrain dopamine neurons suggested that a key function of dopamine is to transmit reward prediction error signals – a measure of whether events were better or worse than expected based on previous experience. However, not all midbrain dopamine neurons appear to encode similar information in their activity patterns.

Ionotropic receptors

In the absence of synaptic partners, each specialization has the intrinsic capacity to assemble morphological rudimentary structures. Which side initiates synaptic cross-talk in vivo depends on the neuronal types and specific synapses. Cell-surface proteins, such as neurexin and neuroligins, and secreted proteins, such as laminins, have long been studied for their roles in specifying synaptic connectivity. Four reviews in this series cover recent advance in understanding the molecular complexity of synaptogenetsis and synapse maintenance, and present complementary insights on the same molecule in distinct neuronal circuits and from different model organisms.

Sakers and Eroglu focus on the neuroligin protein family, which are ligands for neurexins and were previously thought to be only produced from neurons and reside in postsynaptic compartment. However, a series of recent papers have demonstrated that astrocytes produce neuroligin 2 and that the glial produced neuroligins not only regulate synaptogenesis and synapse transmission but also contribute to disease pathogenesis and glioma. Lastly, Connor et al. provide a comprehensive review on how the vertebrate-specific immunoglobulin superfamily proteins known as MDGAs interact with neuroligins to suppress synapse development. MDGAs are tethered to the membrane through a GPI anchor, and MDGA–neuroligin interactions occlude neuroligin–neurexin binding. As accumulating evidence links mutations in these molecules to various neurodevelopmental and neuropsychiatric disorders, these reviews are timely and point to many questions for future investigation.

The fourth topic area is post-traumatic stress disorder and the role played by neurons in the locus ceruleus in its manifestations. The last topic area is chronic pain states and the impact these have on the circuitry of the ventral striatum. Our laboratory conducts multiple-single neuron recording experiments using chronically implantable microdrives in rabbits as they perform eye blink conditioning, an associative memory task. We take advantage of an integrated approach combining several techniques such as paired recordings from anatomically identified neurons, optogenetic, immunohistochemistry, light and electron microscopy applied to wild-type and transgenic animals. We use these techniques to test hypotheses about the neurophysiological properties and the functional role of neurons from brain regions that are involved in associative memory such as the prefrontal cortex, hippocampus, thalamus, and the basal ganglia. Neurobiological research 40 years from now will probably be very different from what it is now, as new methods are developed and new questions asked that are beyond our ability to tackle today.

Yishi Jin is a Distinguished Professor in Neurobiology Section, Division of Biological Sciences and Department of Cellular and Molecular Medicine, the School of Medicine, at the University of California, San Diego. She is the inaugural holder of the Junior Seau Foundation Endowed Chair in Traumatic Brain Injury. She received her BS with honors in Cell Biology at Peking University and her PhD in Molecular Biology at University of California, Berkeley. She carried out postdoctoral work at Massachusetts Institute of Technology. Dr Jin’s lab has pioneered the use of in vivo labeling of synaptic components and employed the powerful genetic analysis in C. Elegans to elucidate conserved molecular pathways regulating synapse formation.

Simulated comparisons of slow and rapid event-related task-based functional connectivity. Poster presented at Society for Biological Psychiatry; San Francisco, CA. Activity flows over task-evoked networks shape cognitive task activations across task switches. Poster presented at Cognitive Neuroscience Society, San Francisco, CA.

MRNAs encoding a number of transmembrane proteins, including ion channels, are found within the presynaptic transcriptome and protein translation machinery is present in mature axons. Biever et al. review recent evidence supporting presynaptic translation and intra-axonal synthesis of transmembrane proteins. The complexity of localized translational control lies in the dynamic interaction between regulatory elements embedded in the transcript and a rich toolbox of transacting factors, including translational machinery components, RNA binding proteins and miRNAs. Heterogenity of ribosomes may underlie compartmental-specific local translation. Improvements in imaging technology has enabled tracking of mRNPs, which are made of higher-order assemblies of RNAs and proteins with unprecedented temporal resolution Das et al. review both visualization and bioinformatic methodologies for analyzing neuronal mRNPs. For example, an algorithm based on Bayesian model selection and Hidden single-molecule detection Markov Modeling helps to characterize the transient transition states of individual mRNA transporting granules, and captures the real-time dynamics of protein synthesis in living neurons.

There are so many diverse opportunities to engage in neuroscience research at MIT that the options can be somewhat overwhelming. She completed her postdoctoral work at the University of Michigan, where she developed a modular biomaterial system for gene, drug, and stem cell delivery to promote repair after spinal cord injury. In 2020, Dumont was awarded the inaugural Junior Frost Fellow Award in chemistry for her targeted drug delivery strategies following nerve injury. We use an interdisciplinary approach in this research, using a combination of behavioral, biomechanical, and neurophysiological techniques. Our current research examines the neural control of internal joint variables, evaluating the hypothesis that the nervous system actively regulates the stresses and strains within joints in order to minimize injury. We want to understand how neural circuits across many brain areas interact to support decision making.

Of the many types of neurotransmitter used in the brain, dopamine has a privileged role, particularly in the striatum. The machineries responsible for controlling dopamine secretion is reviewed by Liu and Kaeser. The conversion of the secreted chemical signal back into an electrical one is carried out in dendrites. The initial detection of a given neurotransmitter on the postsynaptic dendrite is usually handled by ionotropic receptors, assembled into complexes that determine the precise localization and turnover of these ion channels. Tomita reviews what is currently understood regarding GABA receptor assemblies and how this impacts function.

Although our understanding of the biochemical under-pinnings of synapse function has made significant strides, detailed mechanistic understanding of the biochemical machinery remains at the frontier of molecular neuroscience. As chemical synaptic transmission is usually triggered by an abrupt change in local membrane potential, the details of how different ion channels sculpt the action potential as it travels down the axon is an exciting new area reviewed by Alpazar et al. Unc13, a protein discovered in the original and most powerful genetic screen in C. Elegans, is crucial for all known forms of chemical synaptic transmission. Dittman reviews the many mysteries that have emerged in understanding exactly how this protein controls the exocytic protein machinery.