NeuroFutures2019 Conference Program
(See here for more information on speakers)
(Click here to download a copy of the poster summaries)
Thursday July 11th.
3-5pm. NeuroFutures Workshop.
Location: OHSU Knight Cancer Research Building 2720 SW Moody Ave. Portland, OR 97201
7pm. Public Lecture: Child’s Play: Brain Science to Promote Optimal Development in Early Childhood. Phil Fisher, PhD.
Location: Oregon Museum of Science & Industry (OMSI). 1945 SE Water Ave, Portland, OR 97214
(This is a free event but please register here)
8pm. Post-Lecture Reception (Registered NeuroFuture2019 Conference attendees only)
Location: Mt Hood Brewing Company, 401 SE Caruthers St. Portland, OR 97214
Friday July 12th
(OHSU Knight Cancer Research Building; 2nd Floor Auditorium)
7:30 Breakfast
8:15 Welcome
Session 1: Aging & Senescence. (Moderator: Steven Kohama, OHSU/ONPRC)
8:20 Joe Quinn (OHSU): Precision medicine for neurodegenerative disease?
8:50 Jason Cai (Yale): Fulfilling the Potential of SV2A PET in Early AD detection through the Development of New Tracers.
Synapse loss is one of the earliest hallmarks of Alzheimer’s disease. SV2A PET has shown promise as a biomarker for the synapse loss in MCI/AD patients. To allow for multicenter clinical trials to validate this imaging approach for early AD detection, we are developing new SV2A PET tracers with longer half-lives.
9:10 Vivek Unni (OHSU): Alpha-synuclein and neurodegeneration in Lewy body disorders: Opening a new (cranial) window onto an old problem.
Alpha-synuclein aggregation occurs in many important neurodegenerative conditions, including Parkinson’s Disease, Dementia with Lewy Bodies and some forms of Alzheimer’s Disease, however, the role that this aggregation plays in the disease process is still poorly understood. Our lab has pioneered in vivo imaging techniques in mouse using multiphoton microscopy to study the process of alpha-synuclein aggregation and its functional consequences in living brain.
9:30 Jason Snyder (UBC): Neurogenesis and cellular heterogeneity in the dentate gyrus.
The relevance of adult neurogenesis for humans is unclear since few neurons are born in old age, even in rodents. However, heterogeneous properties of neurons born at different stages of life may make important contributions to hippocampal functions in memory and mood.
9:50 Henryk Urbanski (OHSU/ONPRC): Neuroendocrine Rhythms in Reproduction and Aging
10:10 Coffee break
Session 2: Neurodevelopment. (Moderator: Philip Copenhaver, OHSU)
10:30 Colin Studholme (UW): How human brains begin to differ before birth: MRI studies of normal fetal brain development.
Early in pregnancy all human brains are similar in size and shape, but by the end of pregnancy they are already highly individualized with unique patterns of regional brain size, shape and folding. These regional anatomical differences have potentially been created by the interaction of many factors accumulated over the pregnancy including maternal and fetal hormones, genes, maternal diet and the environment. Computational MR imaging and image analysis techniques have begun to allow larger scale, high yield, high resolution imaging studies of the brain even in the presence of significant fetal head motion. In this talk we will look at measures regional brain growth trajectories and how they relate to basic biological variables, to begin to quantify and explain some of the normal variability seen emerging during pregnancy.
11:00 Kevin Wright (OHSU): Dystroglycan is a multifunctional scaffold for CNS development.
Dystroglycan is a highly glycosylated transmembrane protein, and defects in its glycosylation lead to dystroglycanopathy, a form of congenital muscular dystrophy that is frequently accompanied by a wide range of neurodevelopmental defects. Our lab has used conditional deletion of dystroglycan and mouse models of dystroglycanopathy to investigate how dystroglycan regulates neuronal migration, axon guidance, and synapse formation. We find that dystroglycan functions in the CNS as an extracellular scaffold that binds multiple Laminin G-domain containing proteins to regulate basement membrane integrity, secreted axon guidance cue localization, and axon guidance receptor function.
11:20 Elinor Sullivan (UO/ONPRC): Maternal Metabolic and Nutritional Influences on Offspring behavior Offspring Risk for Neuropsychiatric Disorders.
In a non human primate model, exposure to maternal obesity and poor nutrition influences brain development resulting in long-lasting changes in behavior including increased anxiety and impaired social behavior. These findings indicate that poor maternal nutrition initiates a fetal environment that may result in neural reprogramming and predisposes offspring to pediatric neurodevelopmental and metabolic disorders.
11:40 Bonnie Nagel (OHSU): Disentangling Neurobiological Risk from Consequences of Adolescent Alcohol Use.
Certain neurobiological features are associated with known risk factors for alcoholism, and also predict adolescent alcohol use. Alcohol use itself impacts the adolescent brain. Using prospective, longitudinal studies we are disentangling these risk features from the consequences of use.
12:00 Lightning Talks
12:20 Lunch
1:15 POSTER SESSION 1
Session 3: Cells and circuits. (Moderator: Larry Sherman, OHSU/ONPRC)
2:45 Alan Koretsky (NINDS/NIH): Localization of Laminar Sites of Cortical Plasticity by MRI
Functional MRI techniques have found widespread use to measure brain neural circuits that are used for a large number of behaviors. When circuit activity changes due to plasticity, it remains a challenge to identify sites of synaptic changes responsible for the circuit level changes measured. Of particular interest are the cases of long range cortical rearrangements that have been detected in the human brain after injury. Rodent models that mimic some of these cortical rearrangements have been developed and are being used to determine the synaptic basis for the plasticity detected. We have developed a model of adult cortical plasticity due to peripheral sensory nerve damage that is being used to develop MRI tools that can pinpoint sites of synaptic changes. A combination of functional MRI and laminar specific neural track tracing using manganese enhanced MRI (MEMRI) predicted where changes in synaptic strength may be occurring. Slice electrophysiology has been used to confirm and study the mechanisms underlying the plasticity observed. Prospects for translating MEMRI to humans will be discussed.
3:15 Yun Wang (AIBS): Whole-brain reconstruction and classification of single spiny claustral neurons and L6b_PCs of Gnb4 Tg mice.
The claustrum is a thin, irregular, sheet-like neuronal structure hidden beneath the inner surface of neocortex, which both receives input from and projects back to almost all regions of cortex. Although the specific long-range inputs and outputs of the claustrum have been described in detail for the mouse, the morphologies and projections of individual claustrum neurons are not yet known. I will describe our work to describe and classify claustrum neuron types based on their morphologies using computation-assisted morphological reconstructions to obtain the full extent of dendrites and axons of 100 single neurons in the claustrum and layer 6b across multiple cortical regions. Spiny claustrum neurons (CLA cells) were preliminarily classified into 2 types, with 2 subtypes each, characterized by ipisilateral projections in one, and ipsi- and contra-lateral projections in the other subtype. The morphological features of fully reconstructed spiny claustrum neurons support the hypothesis that these neurons take in information from across cortex and widely disperse this information across cortex, somewhat reminiscent of neuromodulatory systems. The morphological features of fully reconstructed single neurons suggest that axonal and dendritic morphologies, especially the long axonal projections, vary according to soma locations, indicative of a topographic organizational principle in the neuronal networks in claustrum and neocortex.
3:35 Emily Sylwestrak (UO): Habenula neuron populations encoding expectancy and outcome.
3:55 Rebecca Hodge (AIBS): Cell type diversity in human cerebral cortex.
Elucidating the cellular architecture of the human cerebral cortex is central to understanding our cognitive abilities and susceptibility to disease. We established robust methods for cell type classification in human brain using single nucleus RNA-sequencing and performed comparisons of cortical cell types that reveal conserved and divergent features of human and mouse cerebral cortex.
4:25 Fred Rieke (UW): Retinal coding of natural inputs.
Signaling in neural circuits relies on a diverse collection of cellular and synaptic mechanisms. Experimental work often tries to manage this complexity by using stimuli designed to isolate individual mechanisms. But responses to natural stimuli—the stimuli that sensory circuits evolved with—are poorly explained by responses to such simplifying stimuli. This failure—a substantial limitation to our mechanistic understanding of sensory function—likely arises because the complex spatial and temporal structure of natural stimuli reveals contributions of unknown circuit mechanisms or causes known mechanisms to interact in unexpected ways. Key aspects of natural stimuli include strong spatial and temporal correlations, asymmetric distributions of positive and negative contrasts, and large variations in luminance and contrast across space and time. Reliably encoding such stimuli depends on cellular and circuit mechanisms that create selectivity for particular stimulus characteristics over others and match neuronal gain to the range of prevailing inputs. I will describe recent work aimed at identifying the nonlinear mechanisms that are most strongly engaged by natural stimuli, how coactive mechanisms interact, and how they contribute to the coding in the retinal output.
6pm Neurofutures Reception. Patio of the OHSU Knight Cancer Research Building
Saturday July 13th
7:30 Breakfast
Session 4: Building blocks of neural systems. (Moderator: Bill Rooney, OHSU)
8:20 Andreas Linninger (Univ. Illinois, Chicago): The digital cerebral microscope: Using in-silico brain replica to quantify cortical blood flow and oxygen exchange.
The talk will highlight blood flow and oxygen exchange simulations in the human and the mouse cortex at an unprecedented scale using neuroimage data as well as digital replica generated with vascular synthesis algorithms. Computation analysis of blood flow coupled with oxygen kinetics serves as a digital microscope for exploring functional mechanisms of the cerebral microcirculation and to investigate subvoxel hemodynamic and metabolic phenomena.
8:50 Itamar Kahn (Technion): Whole-brain Functional Imaging of Behaving Mice: From Sensation to Goal-Directed Action.
Functional MRI is used pervasively in human brain research, enabling characterization of distributed brain activity underlying complex perceptual and cognitive processes. However, it has been limited in utility in rodents. I will present whole-brain functional imaging of head-fixed mice performing go/no-go odor discrimination, detailing the brain regions subserving this behavior from the naïve state to task proficiency including learning of rule reversal.
9:10 Josh Siegle (AIBS): An open, standardized database of spiking activity across the mouse visual system.
As part of our ongoing effort to understand the function of cortical circuits, the Allen Institute has recently extended our "Brain Observatory” paradigm to the domain of electrophysiology. In October 2019, we plan to release data from dozens of experiments in which we use Neuropixels probes to simultaneously record spike trains from up to 9 visual areas in awake mice.
9:30 Eric Shea-Brown (UW): What makes high-dimensional networks produce low-dimensional activity?
There is an avalanche of new data on the brain’s activity, revealing the collective dynamics of vast numbers of neurons. In principle, these collective dynamics can be of almost arbitrarily high dimension, with many independent degrees of freedom — and this may reflect powerful capacities for general computing or information. In practice, neural datasets reveal a range of outcomes, including collective dynamics of much lower dimension — and this may reflect other desiderata for neural codes. For what networks does each case occur? Our contribution to the answer is a new framework that links tractable statistical properties of network connectivity with the dimension of the activity that they produce. In tandem, we study how features of connectivity and dynamics that impact dimension arise as networks learn to perform basic tasks. I’ll describe where we have succeeded, where we have failed, and the many avenues that remain.
9:50 Santiago Jaramillo (UO): Neural pathways for adaptive sound-driven behavior.
I will describe studies in mice addressing the role of auditory thalamic, cortical, and striatal circuits in behaviors that require rapid adaptation in the interpretation of sounds.
Session 5: Multiscale neural representation of sensory and memory information. (Moderator: Sheri Mizumori, UW).
10:30 Mark D’Esposito (UC/Berkeley): The Modular Brain.
The brain is widely assumed to be a modular system. In this talk, I will discuss a series of empirical findings from fMRI studies that begin to elucidate the neural architecture of modular processing by showing that brain modules execute discrete processes and connector hubs are likely integrating and sending information across modules in support of goal-directed cognition. I will also discuss how a better understanding of this type of large scale organization of the brain may lead to new approaches in the diagnosis, treatment and rehabilitation of cognitive) disorders.
11:00 Dasa Zeithamova Demircan (UO): Specific and generalized memories representing conceptual knowledge
Memory allows us to remember specific past events and accumulate information over time to form generalizable knowledge. Hippocampus has been long known to support memory specificity while generalization has been attributed to other memory systems. I will discuss findings showing that hippocampus also contributes to memory generalization to inform a range of memory-based decisions. Hippocampus represents events simultaneously at multiple levels of specificity through interactions with distinct cortical regions, making it possible for a single structure to form generalizable knowledge while also retaining specific details.
11:20 Beth Buffalo (UW): Reconciling the Spatial and Mnemonic Views of the Hippocampus
While it has long been recognized that medial temporal lobe structures are important for memory formation, studies in rodents have also identified exquisite spatial representations in these regions in the form of place cells in the hippocampus and grid cells in the entorhinal cortex. It has been unclear to what extent these spatial representations are present in the primate brain and how to reconcile these representations with the known mnemonic function of this region. I will discuss a series of experiments that have examined neural activity in the hippocampus and adjacent entorhinal cortex in monkeys performing behavioral tasks including spatial memory tasks in a virtual environment. These data demonstrate that spatial representations can be identified in the primate hippocampus, and that behavioral task structure has a significant influence on hippocampal activity, with neurons responding to all salient events within the task. Together, these data are consistent with the idea that activity in the hippocampus tracks ongoing experience in support of memory formation.
11:40 Mark Cembrowski (UBC): Deconstructing memory at a cell-type-specific resolution.
We provide a coherent molecular-, cellular-, circuit-, and behavioral-level demonstration that the mammalian hippocampus embeds structurally and functionally dissociable streams to subserve working memory
12:00 Lightning Talks
12:20 Lunch
1:15 POSTER SESSION 2
Session 6: Risk, emotion & substance abuse. (Moderator: Bita Moghaddam, OHSU)
2:45 Marina Wolf (OHSU): Vulnerability to craving and relapse during abstinence.
A major difficulty in treating drug addiction is that addicts remain vulnerable to craving and relapse for long periods of time after abstinence is achieved. I will discuss a rodent model of persistent drug craving during abstinence, with a focus on neuronal plasticity in the reward circuitry that maintains high levels of craving.
3:15 Sam Golden (UW): Aggression reward and relapse: behavioral, cellular and systems approaches.
Aggression is an ethologically complex behavior with equally complex underlying mechanisms. Here, I present data on one form of aggression, appetitive or rewarding aggression, and the behavioral, cellular and system-level mechanisms guiding this behavior. I will briefly highlight recent advances in computer vision and machine learning for automated scoring of aggressive behavior, the role of specific cell-types in controlling aggression reward, and close with preliminary data on the whole brain aggression reward functional connectome using light sheet fluorescent microscopy
3:35 Andrey Ryabinin (OHSU): Alcohol drinking in unconstrained socially-housed rodents.
Although social environment is well known to affect alcohol and drug self-administration, previous research was not able to truly monitor drug intake in socially-housed animals. I will describe our recent findings from studies using radiofrequency tracking of socially-housed mice and prairie voles as well as the consequences of these findings.
3:55 Vincent Costa (OHSU): A Comparison of amygdala and striatal contributions to reinforcement learning.
Traditional views of reinforcement learning emphasize the central role of the ventral striatum in integrating dopaminergic signals to facilitate learning, but only ascribe the amygdala a minor, modulatory role. I will discuss a series of experiments in non- human primates that overturn this view. These experiments combine computational modeling of choice behavior in multi-arm bandit tasks with excitotoxic lesions and neurophysiological recordings to discern the relative contributions of the amygdala and ventral striatum to reinforcement learning during reversal learning and explore-exploit tradeoffs. Overall, these data provide evidence that both conceptual and computational models of reinforcement learning should be revised to incorporate a more prominent role for the amygdala and its interaction with the ventral striatum.
4:15 Poster Awards
4:30 Closing remarks – US Congressman Earl Blumenauer
4:45 Adjourn
AIBS: Allen Institute for Brain Science
OHSU: Oregon Health & Science University
ONPRC: Oregon National Primate Research Center
UBC: University of British Columbia
UO: University of Oregon
UW: University of Washington/Seattle