Spring 2007 Seminar Series in Neuroscience

Dr. Linda Watkins, Distinguished Professor, Dept of Psychology, University of Colorado at Boulder

TITLE: “Curing chronic pain: New hope on the horizon?”

Abstract: It has been estimated that 1 in 4 adults will suffer from chronic pain. Over the past decade, there has been growing recognition that glia (astrocytes &/or microglia) are key players in the creation & maintenance of clinically relevant pain states. Here, hot, cold, & hard pressure pains are greatly amplified; warm, cool & light touch are now perceived as pain. Currently available drugs used to treat such pain fail to adequately treat the pain. We believe that the reason these drugs fail is that they target neuronal, rather than glial, activation. Development of novel strategies to selectively target glial activation &/or the neuroexcitatory products they release holds great promise for clinical pain control.
Very recently, it has also been recognized that glia become activated in response to common opioid analgesic (pain suppressive) drugs, such as morphine & methadone. Importantly, this glial activation in response to opioid drugs compromises the acute analgesic efficacy of these clinically relevant drugs. Indeed, glia become more & more activated in response to repeated opioids, contributing to the progressive loss of analgesic efficacy (i.e. opioid tolerance) & progressive dependence on ongoing opioid availability without which withdrawal occurs. So, not only do glia potentiate pain, they also hinder the effectiveness of opioids intended to suppress pain. Taken together, current data strongly implicate glia in pathological pain, opioid tolerance, & opioid dependence/withdrawal. This suggests that novel clinically relevant therapies that target glial activation &/or their neuroexcitatory products may greatly improve clinical pain control & aid addicts in escaping their dependency on opioids. As a drug that targets glia has now entered clinical trials for pain, & will likely soon enter clinical trials for enhancing the efficacy of morphine, there may be new hope on the horizon for controlling human chronic pain.

Dr. Tiffany Ito, Professor, Department of Psychology, University of Colorado at Boulder

TITLE: “The Social Neuroscience of Stereotyping and Prejudice”

Abstract: Knowing that someone is of a particular race or gender can automatically activate a host of beliefs (e.g., that he or she may be aggressive) and feelings (e.g., dislike) which in turn influenced how we treat them. A variety of behavioral methods have been used to examine this issue, but with the continued development of neuroscience methods and theories, we now also have the opportunity to approach these questions from a more explicitly neuroscientific perspective. We have used neuroimaging methods (e.g., event-related brain potentials and fMRI) to study the early perceptual and later behavioral implications of race and gender information. We find that race and gender cues have relatively fast and obligatory effects on attention, influencing early perceptual processes across a range of tasks, helping us to understand the relatively pervasive effects that social category information often has on behavior. We have also begun to examine how early attentional differences in the processing of social category information relates to the subsequent activation of stereotypes and prejudice. Finally, we have used neuroimaging methods to examine possible mechanisms through which stereotyping and prejudice can be controlled or inhibited. Together, the results highlight the complex, multi-faceted nature of social perception, and also provide insights into mechanisms of change related to stereotyping and prejudice.

Dr. Amy Palmer, Professor, Department of Chemistry and Biochemistry, University of Colorado at Boulder

TITLE: “Calcium biosensors illuminate cellular perturbations in Alzheimer's disease models”

Abstract: Both sporadic and inherited cases of Alzheimer’s disease include perturbation of one of the most important and fundamental cellular signals, namely Ca2+ homeostasis. Calcium signaling controls critical processes such as cell growth and survival, proliferation, and differentiation. It is therefore not surprising that perturbations in calcium signaling can have profound consequences for a cell. While the connection between calcium and Alzheimer’s disease is well documented, the details of how altered calcium contributes to Alzheimer’s disease pathology have not been elucidated. The clinical mutations that give rise to the inherited (familial) form of Alzheimer’s disease have proven extremely useful in helping the research and medical communities better understand the cellular changes that accompany disease progression. Given the complexity of Alzheimer’s disease, it is striking that 63 % of the mutations identified cluster in the protein presenilin. The primary question we seek to address is how these mutated proteins give rise to the multitude of symptoms associated with Alzheimer’s disease, and in particular how they contribute to Ca2+ dyshomeostasis. Our approach is to use fluorescence microscopy and Ca2+ sensors to characterize Ca2+ signals in defined cellular locations in cultured cells expressing either wild type (wt) or mutant presenilin. To accomplish this, we have designed a family of genetically encoded calcium sensors (called cameleons) that can quantitatively monitor calcium dynamics in distinct subcellular locations such as the ER, mitochondria, and plasma membrane.

Dr. Michael Fanselow, Professor, Department of Psychology, UCLA, Los Angeles, CA

TITLE: “Competition and Compensation in the Circuitry Mediating Contextual Fear”

Abstract: Environmental threats, such as the risk of predation, likely represent the most urgent costs to survival of a species. Evolution has little tolerance for failure when it comes to defense. To cope with such risks, mammals evolved a potent fear motivated defensive behavioral system with certain unique learning abilities. For example, the system is capable of one-trial learning that shows no forgetting over the lifespan of the animal. Thus after receiving a single aversive experience (shock) in a particular place, rats will display defensive freezing when returned to the shock context regardless of how long ago this experience occurred. Current models of contextual fear learning are based on the idea that there is an essential neural circuit that accomplishes this remarkable ability. There is considerable support for this notion of a highly specialized and dedicated circuit that includes the hippocampus, which encodes a representation of the place or context, and the basolateral amygdala (BLA), which encodes the emotional significance of the aversive event. This model predicts that damage to this circuit should abolish acquisition and expression of contextual fear learning. While this is generally true for post-training lesions (expression) the results for pretraining (acquisition) are less consistent. It appears that when the hippocampus or BLA are compromised other structures can assume their function. However, these alternative neural routes only become important when the primary pathway is compromised, they are less efficient than the primary pathways, and learning with these alternative pathways loses many of the highly adaptive features of normal fear learning.