Intracellular calcium encodes spatial and temporal information in neurons. I will discuss my lab’s work on the mechanisms of cellular calcium signaling through the nicotinic acetylcholine receptor in growing axons. This research aims to provide an understanding of principles that underlie connectivity in the nervous system.]]>
Other things being equal, people will accept less reward in the near term instead of more in the long run. This behavior is called discounting the future (or simply discounting) and is a cornerstone of both practical finance (interest rates!) and theoretical models in economics. It is known that the only consistent way for an individual to discount the future is exponentially at constant rate. To do anything else induces changes in behavior part way through the time period over which discounting is occurring, leading to inconsistent behavior. However, a wide variety of behavioral experiments clearly demonstrate that people are not exponential discounters, but rather discount the near term more than the long run, which may lead to inconsistent behavior over time. In this talk I will present a novel theory for such ‘hyperbolic’ discounting and demonstrate that, far from being exceptional, ‘anomalous’ discounting is a generic feature of human behavior. I will show how experimental data on discounting behavior can be represented mathematically using the theory. The formalism can be given ‘multiple selves,’ ‘competing substructures,’ and risk-based interpretations, and is capable of rationalizing old adages like ‘A bird in the hand is worth two in the bush.’ The mathematical formalism leads naturally to social questions, concerning how groups or whole societies discount collectively. I will show that fMRI, laboratory, survey, and natural experiment data concerning how people value the future can be rationalized in terms of the new theory, and will conclude by applying it to a broad range of real-world problems including climate change and the term structure of interest rates.]]>
The basal ganglia is a collection of brain areas involved in normal learning and motor behavior as well as diseases such as Parkinson’s disease, and addiction. The striatum of the basal ganglia is a major site of learning and memory for goal directed actions and habit formation. Spiny projection neurons of the striatum integrate cortical, thalamic, and dopaminergic input to learn critical associations.
The tendency to relapse after withdrawal from addiction is partly due to the strong habits learned from the overly strong dopamine stimulation caused by drug use. In contrast, the death of dopamine neurons projecting to the striatum is the cause of Parkinson’s disease. Thus, understanding the role of dopamine in normal motor learning will also elucidate mechanisms underlying Parkinson’s and drug relapse. One mechanism used by striatal spiny projection neurons for learning and memory storage is synaptic plasticity.
I will discuss computational and experimental investigations on how dopamine and different patterns of synaptic input control the direction of synaptic plasticity, the signaling molecules involved in discriminating spatial and temporal patterns, and the extent of spatial specificity of synaptic plasticity.]]>
Historically, the field of Computer Science has developed from the fields of mathematics and engineering. While the influence of these fields continues to be quite strong, there is an increasing interest in developing new computational techniques based on inspiration from nature. Examples include artificial neural networks, evolutionary algorithms, and ant colony optimization. In this lecture I describe some of the more popular nature-inspired techniques, illustrate their behavior through examples, and discuss some important problem areas to which they are being applied.]]>
Although most neuroscientists have yet to embrace a culture of data sharing, the decade-long success story of NeuroMorpho.Org demonstrates how publicly available repositories may benefit data producers and end-users alike. NeuroMorpho.Org is a centrally curated repository of digital reconstructions of axonal and dendritic morphology hosting freely accessible light- and electron-microscopy tracing data contributed by >200 laboratories worldwide from 450+ peer-reviewed publications. This database continuously grew from 1000 neurons released in v1.0 in 2006 to over 50,000 in v.7.0 (September 2016), spanning 35 species, 40+ brain regions, and ~150 cell types. More than 5 million neuronal reconstructions (approximately 30 km of traced axons and dendrites) have been downloaded to date over hundreds of thousands of unique visits from 153 countries. For perspective, producing an equivalent amount of data would take a skilled neuroscientist over 700 centuries of labor. In addition to the documented scientific impact in terms of novel published discoveries based on data in the repository, NeuroMorpho.Org has been showcased in textbooks and Massively Open Online Courses, the China Applied Math Olympiads, multimedia outreach including Neuroscience for Kids, Scientific American online, and popular blogs, and a dedicated testimony to the White House Bioethics commission. Nonetheless, in this era of Big Data and open source initiatives blooming all over the world, neuroscience trails far behind. A troubling majority of authors reporting neuronal reconstructions in peer-reviewed articles flatly declines to share their data upon request. Thus, most collected data remain unavailable to the broader research community, causing a substantial loss of time, money, and missed scientific opportunities.]]>
The Physiological and Behavioral Neuroscience in Juveniles (PBNJ) laboratory focuses on relating changes in brain function to changes in cognitive ability during the postnatal period. We are a highly interdisciplinary laboratory tampering with genes, fiddling about with proteins and cells, poking and prodding at the physiological level, and assessing behavior in rodent models. We also train little wormy critters to jump through hoops and piece together little DNA snippets to make better optical physiological tools. All of this plays during matinees and nightly here at the Krasnow Institute. No tickets are necessary to observe, just wide eyes and an open mind.]]>
Parahippocampal connections with posterior parietal cortex and the thalamus are well documented for the rodent and primate brains, but there are many open questions about the functions of these circuits. In the rodent brain, the postrhinal cortex, posterior parietal cortex , and the lateral posterior nucleus of the thalamus (LPO) are robustly interconnected. Similar patterns of connectivity are evident in the primate parahippocampal cortex (postrhinal homolog), posterior parietal cortex, and the pulvinar (LPO homolog). We used neuroanatomical tracing in combination with electrophysiology and optogenetic manipulations in behaving rats to address the function of the posterior parietal cortex in this circuit. I will present evidence that both the posterior parietal cortex and the LPO are important for translating visual information into appropriate behavioral actions. I will also show functional differentiation in the rat posterior parietal cortex such that dorsal and caudal subdivisions contribute differently to stimulus driven attention. These findings have implications for the role of the posterior parietal cortex in memory and other cognitive functions.]]>
Non-invasive specific control of brain activity requires the observation of generic brain dynamics, the identification of brain states, the selection of appropriate stimuli, and the actuation of stimuli. In collaboration with a number of researchers at Mason we have made significant headway on all of these fronts and are working towards closed-loop neuronal control systems for the treatment of neuropathologies such as epileptic seizures.]]>
Understanding how genetic variation manifests itself as phenotype is major unanswered question in biology. We explore this issue in the context of heart disease. A certain class of cardiac arrhythmia results from defects in intracellular calcium dynamics. Of these many can be attributed to genetic mutations in proteins in calcium cycling. Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT1-5) has variants depending upon the calcium cycling protein involved. In this disease patients are seeming normal, however unexpected they can suffer a fatal arrhythmia during or immediately following exercise or stress. We specifically used multiscale computational models to study CPVT1 and CPVT2 which result from defects in the ryanodine receptor type 2 (RyR2) and calsequestrin (CASQ), respectively. These mutations increase the open probability of the RyR2 under resting conditions and to a much greater during β-adrenergic stimulation. The proposed mechanism for this type of arrhythmia is that the combination of increased sarcoplasmic reticulum (SR) Ca2+ load and increased RyR2 open probability during β-adrenergic stimulation can lead to large spontaneous Ca2+ release events resulting in arrhythmia. However, this raises a paradox. One expects considerations of changes in Ca2+ pump-leak balance across the SR due to the CPVT and the consequent changes in Ca2+ pump-leak balance across the sarcolemmal membrane to be largely self-correcting. Our multiscale computational model explores these mutations and offers explanations behind the mechanism of arrhythmia in CPVT1-2.
Talk starts at 4:00 PM (Krasnow Building, Room 229)]]>