2012-2013

 

Meta-affective processing and its relationship to serotonin and BDNF systems

Lauren A. Demers (Neuroscience-Honors)

Advisor: Nancy Koven

Emotional intelligence (eIQ), a normally-distributed, multi-faceted construct, describes one’s ability to monitor emotions in self and other, discriminate among feeling states, and regulate emotions. As low eIQ is often considered a risk factor for mood and anxiety disorders, there is clinical value in understanding the biological contributions of eIQ. Interestingly, while the neurochemistry of affective disorders, particularly with respect to brain-derived neurotrophic factor (BDNF) and serotonin (5-HT) systems, is well studied, the relationship between these two neurotransmitters and facets of emotion processing across the full continuum of eIQ levels is unknown. In this study, peripheral levels of BDNF and 5-HT, self-report (Toronto Alexithymia Scale, Mood Awareness Scale, Trait Meta-Mood Scale) and performance-based indices of emotional intelligence (Mayer-Salovey-Caruso Emotional Intelligence Test) and other aspects of affective processing (Questionnaire Measure of Emotional Empathy, Reading the Mind in the Eyes Test, Auditory Emotional Stroop Test)were measured in a non-clinical, young adult sample to test the hypothesis that high levels of BDNF and 5-HT are associated with high eIQ and superior affective processing skills. While BDNF was related to poor emotion management, higher serotonin levels were associated with superior self-report and performance-based emotional clarity and perceptive ability as well as better performance-based social management skills. Low levels of both BDNF and serotonin were related to a memory bias to recall or recognize negatively-valenced words. The results of this study suggest that serotonin plays a critical role in emotional clarity and perceptivity.

Brain-Derived Neurotrophic Factor in Relation to Executive Functioning and Aerobic Exercise

Larisa R. Collins (Neuroscience)

Advisor: Nancy Koven

Neurotrophins such as brain-derived neurotrophic factor (BDNF) are vital for nerve cell survival and adaptive plasticity. Evidence has shown that there are high BDNF levels in the prefrontal cortex (PFC), a key brain region for aspects of higher-order cognition. More recently, aerobic exercise has been shown to lead to greater executive functioning skills. It is unknown, however, whether BDNF mediates this relationship between exercise and cognition. In this study, 52 young adults completed a battery of executive function tests and performed a Step Test to assess aerobic fitness level. BDNF levels were quantified with an enzyme-linked immunosorbent assay (ELISA) from urine samples taken at time of testing. Individuals who exercise more per week had higher levels of BDNF. Participants with higher concentrations of BDNF performed better in the set-shifting and cognitive flexibility subtests. Although a mediation effect was not found, these results further corroborate a link between aerobic exercise and BDNF levels and further delineate how BDNF is associated with cognition in healthy humans. Perhaps, the genetics of BDNF influence BDNF peripheral expression, thus modulating cognitive flexibility.

Mapping a checkpoint for synaptic vesicle fusion in Caenorhabditis elegans

Samantha Forrest (Neuroscience)

Advisor: Glen G. Ernstrom

Neurons in the brain communicate by sending chemical messages to one another in the form of packets of neurotransmitter molecules, which are released at presynaptic terminals.  Neurotransmitters are stored in specialized sacs, known as synaptic vesicles, which dock at the membrane and release regulated packets, or quanta, of neurotransmitter. However, what regulates how much neurotransmitter is loaded into each vesicle is not fully understood.  It has been hypothesized that vesicles must fill with transmitter in order to fuse.  These vesicles are reliant on a proton electrochemical gradient to serve as the power source for filling the vesicle. The V-ATPase proton pump is responsible for creating this gradient and previous studies have shown that mutations of this pump in the model organism, the nematode Caenorhabditis elegans, block the fusion of vesicles. In this paper, I outline a strategy for testing how the V-ATPase may obstruct vesicles from fusing until they are properly filled and show the tool I have build to test a V-ATPase checkpoint mechanism for vesicle fusion.  By tagging C. elegans V-ATPase subunits with fluorescent proteins, these subunits’ locations can be tracked in vivo.  This tool can be used to test the physical obstruction checkpoint model, which suggests that the V-ATPase protein complex must disassemble in order to fuse.  If this model is correct, then the fluorescence of the disassembled V-ATPase will be more diffuse at the synapse and disassembly can be blocked by disrupting the normal neurotransmitter loading process.

Plasticity in the central control mechanism of the biphasic ventilatory response following developmental hyperoxia: effects of the P2X receptor antagonist PPADS

Corey B. Hill (Neuroscience)

Advisor: Ryan Bavis

The biphasic ventilatory response to acute hypoxia (HVR) has been shown to be a plastic system, responding significantly to developmental oxygen conditions.  Neonatal rats developed in relative hyperoxia express HVRs similar to more mature individuals, suggesting an accelerated development of the system.  Through a comparative analysis of HVR seen in P4 neonates raised in hyperoxia and P14 rats grown in normoxia, this research aims to elucidate the exact physiological changes induced by developmental hyperoxia.  Additionally, it is hoped that an analysis of the P2X inhibitor PPADS will solidify its role as a robust method for isolating CNS respiratory control by inhibition of carotid body activity.  These data will add to the growing understanding of developmental respiratory plasticity that has far reaching implications, especially in the realms of neonatal care for humans.

Dominant and subordinate male odors elicit different patterns of synaptic and intrinsic plasticity in accessory olfactory bulb mitral cells of female mice

Samantha Marie Landino (Neuroscience-Honors)

Advisor : Jason Castro

The accessory olfactory bulb (AOB) is a sensory brain region critical for detecting and discriminating between socially relevant chemical signals from conspecifics. Additionally, the AOB is a well-established locus of social memory, with long-lasting, well-localized, and stimulus-specific physiological changes capable of decreasing AOB output upon reactivation by a specific odor. I investigated whether such plastic changes in the AOB are selectively induced by the odors of dominant, but not subordinate individuals, to characterize a hypothesized, but unidentified memory for signals conveying social rank. I established social hierarchies in male mice using the tube test to identify dominant and subordinate individuals. Female mice were reared for nine days on bedding from the cages of dominant or subordinate males. Following rearing, in vitro whole-cell recordings from female AOB slices were used to determine how dominant vs. subordinate male odors alter intrinsic and synaptic properties of AOB principal neurons (mitral cells). I found that exposure to both dominant and subordinate male odors is sufficient to induce long-term changes in synaptic properties, namely recurrent inhibition. Additionally, dominant odor exposure tended to decrease neuronal excitability while subordinate odors increased excitability. Together, these results indicate that pre- exposure to dominant male pheromones tends to diminish mitral cell firing, which is known to constitute a particular form of memory, while subordinate pheromones may increase the responsiveness of mitral cells, suggesting that the AOB may selectively prioritize odors from dominant individuals.

Peripheral Levels of Oxytocin and Affective Processing in Relation to Schizotypy

Laura Max (Neuroscience-Honors)

Advisor: Nancy Koven

Schizotypy is conceptualized as the subclinical presentation of schizophrenic psychopathology, and involves affective, cognitive, and perceptual disturbances, as well as impaired social cognition. The neuropeptide oxytocin, which facilitates emotion recognition, bonding, trust, and attachment, is thought to play a role in the etiology of schizophrenia and evidence suggests that reduced levels of oxytocin contribute to the disease. However, it has not been determined if oxytocin abnormalities are detectible in schizotypy. The present study sought to examine the degree of correlation between peripheral levels of oxytocin and self-report indices of schizoptypy in a sample of young adults. Additionally, the influence of oxytocin on the relationship between schizotypy and social cognition was assessed. Tests of social cognition included the Mayer-Salovey-Caruso Emotional Intelligence Test as well as a novel task that assessed emotion recognition derived from the Penn Emotion Recognition Task. Peripheral oxytocin levels were examined with enzyme-linked immunosorbent assay from saliva samples obtained per participant. Correlation and regression analysis indicated that oxytocin levels were positively associated with socioaffective difficulties, and that this relationship was moderated by emotional experiencing abilities as measured by the MSCEIT. This unexpected finding indicates that high levels of oxytocin may contribute to social cognitive impairments in a subset of individuals.

UNC-46 is a synaptic vesicle protein required for GABA neurotransmission in Caenorhabditis elegans

 Amrit Sridhar (Neuroscience)

Advisor: Glen Ernstrom

Neurotransmitters are chemicals made by neurons that relay electrical signals in one neuron to another nearby electrically excitable cell. By molecular mechanisms that are not fully understood, neurotransmitters are secreted in packets: neurotransmitters are loaded into small membraneous sacs called synaptic vesicles, and electrical excitation triggers vesicle fusion to the plasma membrane that unloads synaptic vesicle contents onto nearby cells. Two genes have been identified by genetic analysis in the nematode Caenorhabditis elegans that are involved in loading synaptic vesicles with the neurotransmitter gamma amino butyric acid (GABA). One gene, unc-47, encodes the founding member of vesicular GABA transporters (VGATs). The other, unc-46, is a novel membrane protein whose function has not been resolved. There are two models for UNC-46: one model is that UNC-46 is a protein chaperone that directs VGATs to synaptic vesicles; the other is that UNC-46 is an auxiliary subunit of VGAT that aids VGAT function on synaptic vesicles. Here I show that UNC-46 primarily functions on synaptic vesicles. By tagging UNC-46 with a pH-sensitive green fluorescent protein, pHluorin, and tracking its fluorescence when either organelle pH is disrupted or when synaptic vesicle trafficking is disrupted, we were able to define UNC-46 expression primarily to synaptic vesicles. These results are consistent with UNC-46 functioning as an auxiliary subunit that aids vesicular GABA transport.