Neuromodulatory Effects of Delta Opioid Receptors on Accessory Olfactory Bulb Processing

 Abigail Jane Alexander (Neuroscience-Honors)

Advisor: Jason Castro

The opioids are a diverse set of neurotransmitters that potently modulate synaptic processing as a function of behavioral state. While most studies of opioids have investigated their synaptic actions in the context of analgesia and addiction, few have examined their role in sensory processing. This potential role is especially compelling in the olfactory system, where it was recently identified that there is a robust and unexpected expression of opioid receptors. This suggests that even the earliest steps of sensory olfactory processing may be powerfully modulated by opioidergic inputs. To investigate the synaptic actions of opioids in olfactory processing, I obtained whole cell recordings from mitral cells of the accessory olfactory bulb (AOB) – a brain region critical for detecting and discriminating non-volatile ligands derived from conspecifics. Previous research suggested that opioidergic agonists would decrease recurrent inhibitory activity. Contrary to these findings, I observed a marked effect of DADLE (a delta-opioid receptor agonist) on recurrent excitatory activity when inhibitory input was blocked. Analysis of the intrinsic and passive properties of the mitral cells demonstrated that this increase in recurrent excitation was the result of a synaptic change and not due to a global alteration in cellular excitability or passive properties. Furthermore, examination of spontaneous activity demonstrated a dramatic increase in the frequency of excitatory postsynaptic potentials with DADLE application. Taken together, these results demonstrate that opioids powerfully modulate recurrent excitation in the AOB through a presynaptic mechanism. These findings represent, to the best of my knowledge, a novel mechanism for opioidergic modulation.

Long-term exposure to male status specific odors elicits mitral cell synaptic plasticity in the accessory olfactory bulb of female mice

 Daniel Alexander Birkhead (Neuroscience)

Advisor: Jason Castro

The accessory olfactory bulb (AOB) is a sensory brain area that processes semichemicals derived from kin and conspecifics. Notably, responses of AOB neurons are sensitive to relative social rank, and rearing of females in the odor of dominant vs. subordinate males leads to persistent bidirectional changes in the excitability and recurrent synaptic activity of AOB principal neurons. Here, we sought to identify the precise physiological mechanisms responsible for these changes. We prepared in-vitro slices from the AOBs of females reared in either dominant, subordinate, or control odors, and obtained patch clamp recordings from AOB mitral cells. We pharmacologically isolated recurrent excitatory and inhibitory components of mitral cell activity, and are investigating how the proportions of excitation and inhibition are altered by stimuli conveying social rank.

Comparing the Effects of Helisoma and Mammalian Gonadotropin Releasing Hormone on the Feeding Central Pattern Generator in Helisoma trivolvis

Heather Fisher (Neuroscience)

 Advisor: Nancy Kleckner

The goal of this study was to compare neuromodulation in Helisoma buccal neurons by two forms of the Gonadotropin-releasing hormone (GnRH): the lutenizing hormone-releasing hormone (LHRH) from mammals and a Helisoma GnRH (hGnRH).  Neuromodulatory of effects of LHRH (8.5 mM), hGnRH (10 µM), and hGnRH (1 µM) were determined by measuring changes in membrane potential in B5, B19, and B27 motor neurons from Helisoma trivolvis buccal ganglia using standard intracellular recording techniques.  In B5, inhibitory effects were seen upon neuromodulation with LHRH and 10 µM hGnRH, but excitatory effects were seen with1 µM hGnRH neuromodulation.  GnRH effects in B19 predominantly depended on whether or not B19 was in a dopamine-induced feeding rhythm.  Neuromodulation with all GnRH solutions inhibited B27.  The results suggest that GnRH may not induce a phase 1-2 firing pattern characteristic of substrate cleaning before egg laying, but may have inhibitory effects on feeding.  Results also suggest GnRH may have time dependent effects on G-protein coupled receptors and may have concentration effects due to different binding affinities to different populations of GnRH receptors.

Neuromodulators of the Feeding Behavior Network in Helisoma trivolvis: Mapping of Immunoreactivity in the CNS and Digestive System

 Destany L. Franklin (Neuroscience)

Advisor: Nancy Kleckner

The tripartite feeding behavior of the Helisoma trivolvis pond snail is controlled by a neural network called a central pattern generator (CPG) that produces rhythmic patterned behaviors. The feeding CPG is located in the buccal ganglia of the central nervous system (CNS) within Helisoma. The three phases of the plastic system, S1, S2, and S3 correspond to protraction, retraction, and hyperretraction of a toothed radula. The CPG alternates between the three phases to produce feeding or reproduction behaviors. GnRH, APGWamide, and SCPb are three peptides that have been identified as neuromodulators that influence feeding or reproduction in various vertebrate and invertebrate species. The purpose of this study was to use immunocytochemistry to localize GnRH, APGWamide, and SCPb in the CNS and parts of the digestive system to determine their roles in the feeding CPG. A rabbit anti-human GnRH antibody was immunoreactive in the visceral, cerebral, right parietal and pedal ganglia, salivary glands, and esophagus, but an rabbit anti-Aplysia GnRH was only localized in a bilateral neuron in the buccal ganglia and a single cell body in the visceral with an axon projecting through the right parietal and right pleural ganglia. APGW was immunoreactive in left parietal, visceral and the cerebral ganglia. SCPb was localized to several clusters of neurons across all eleven ganglia. The characterization of the peptides in the CNS and gut of Helisoma here and elsewhere suggests GnRH and APGWamide may facilitate state switching from reproduction to feeding behaviors while SCPb directly modulates the feeding CPG by influencing mechanoreceptors

Glutamate receptors in the feeding rhythm of the pond snail, Helisoma trivolvis

Caleb Glassman (Neuroscience)

Advisor: Nancy Kleckner

The triphasic feeding rhythm of Helisoma trivolvis is produced by a central pattern generator (CPG) in which excitatory and inhibitory connections between interneurons and motor neurons produce a cyclic motor output. The feeding rhythm is patterned by phase 2 inhibition. Phase 2 produces excitation of the phase 2 motor neuron, B27, and inhibition of all other modules of the CPG. Pharmacological evidence suggest that the excitatory effect of phase 2 glutamate on B27 is mediated by AMPA like ionotropic glutamate receptors (iGluRs), whereas its inhibitory effects on the S3 motor neuron B19 occur through metabotropic glutamate receptors (mGluRs) acting on G-protein coupled inward rectifying potassium channels (GIRKs). This study sought to characterize glutamate receptors involved in the Helisoma feeding rhythm using selective mGluR agonists and reverse transcriptase polymerase chain reaction (PCR) amplification of an ionotropic glutamate receptor transcript in identified cells. The mGluR2 agonist, DCG-IV, had no effect on action potential or burst frequency in B19 or B27. The mGluR1/2/5 agonist (1S,3R) ACPD had no effect on action potential frequency in B19 or B27 but resulted in a significant reduction in burst frequency as measured by B19 hyperpolarization. These results suggest the presence of mGluRs on phase 1 or 2 interneurons involved in the generation of the feeding rhythm. PCR amplification identified the presence of Hel-GluR1, an AMPA like iGluR cloned from Helisoma, in the buccal ganglia neurons B19 and B27 but not B5. The presence of Hel-GluR1 on both B19 and B27 may suggest that Hel-GluR1 on B19 receive glutamatergic input from a source other than the S2 interneuron, B2.

Analysis of Cognitive Mediators in the Relationship between Oxytocin and Affective Processing

Carly Hinkle (Neuroscience)

Advisor: Nancy Koven

Social cognition is a broad domain composed of many facets, including emotion recognition, integration of social cues, attention, reading of facial expressions, trust, bonding, and attachment. The neuropeptide oxytocin seems to be a key mediator of social functioning, both in clinical and non-clinical settings. While oxytocin has shown promise as a potential therapy for those with impaired social cognition, it has not yet been determined if too much oxytocin is harmful. It is speculated that, within certain individual difference groups, oxytocin may make emotional stimuli even more salient, prompting hypersensitivity and ultimately withdrawal from social situations. The present study aimed to clarify this conjecture by examining the degree of correlation between peripheral oxytocin levels and affective processing skills in a sample of young adults and, further, to determine if two different executive functions mediate this relationship. Tests of affective processing included the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), the Emotional Stroop Test, and the Reading the Mind in the Eyes Task, while tests of cognitive function included a selective attention test and a novelty detection task. Self-report scales were used to provide additional information about affective individual differences in the sample. Peripheral oxytocin was measured with enzyme-linked immunosorbent assays from saliva samples. Correlation analysis found that oxytocin levels correlated negatively with sensory sensitivity and attention to emotion and that sensory sensitivity itself was correlated with several aspects of affective processing.

An Investigation of the Trends of Neural Noise and its Potential Role in the Impairment of Attentional Brain Circuitry

Emmaleigh T. Loyer (Neuroscience)

Advisor: Jesse Bengson

Several of the causal factors contributing to Attention Deficit Disorder (ADHD) remain unknown, leaving many struggling with the neurodevelopmental disorder. Past electroencephalographic (EEG) studies have suggested that a functional disconnect within attentional brain networks may underlie the generation of abnormal behavior exhibited by individuals with ADHD. In this study, a novel computational data analysis technique was utilized to evaluate the EEG activity recorded from subjects with and without attention deficits in an experiment conducted by Mazaheri et al. in 2010. The slope, 1/f, relating frequency to power, was calculated for all participants as they performed a cross-modal attention task. Contrary to the initial hypothesis, a flatter slope was found at all electrodes sites for participants in the typically developing group. It is suspected that the greater brain variability observed in typically developing children allows them to dynamically adjust to stimuli presented in the cross-modal attention task. It is further hypothesized that the lack of variation found in the brain signal of ADHD subjects may be due to a delay in brain maturation.

Neurocinematics: An Empirical and Theoretical Investigation of Hollywood Mind Control and its Methodological Value to the Progression of Neuroscience

Jane Mayer (Neuroscience)

Advisor: William Seeley

Empirical studies have identified cognitive and affective processes as key, influential components of human perception; yet, an understanding of the complex relationships underlying perception in the context of everyday life has been impeded by methodological constraints. Recent research indicates that the utilization of movie stimuli provides a more naturalistic method for studying perceptual processing. Endowed with the ability to control the presentation of information, and thus develop and manipulate perceptually salient information, movie stimuli provide an accessible way to understand the interrelations between vision, attention, cognition and affect. This review focuses on the ecological value of movie stimuli in understanding the perceptual processing of spatiotemporal sensory information. To do this, the present paper i) acknowledges the differences between viewers’ visual perception within the context of everyday and within the context of movie viewing, ii) identifies the exogenous and endogenous influences that modulate viewers’ spatiotemporal perceptual processing of movies, and iii) uses contemporary findings on visual attention, event segmentation and affective visual processing within the context of everyday to create a viable theory on the ecological validity of using movie stimuli as a means to study cognition. Ultimately, this paper argues that movies—specifically, movies that adhere to heuristics of Hollywood continuity editing rules—are artifacts of ordinary visual perception; and as such, movies illuminate the theoretical possibility of constructing ecologically viable virtual realities within the context of a lab.

Are Emotion-Laden Words Identified More Easily Than Non-Emotional WordsWhen Seen in Continuous Flash Suppression?

Simone Prioli (Neuroscience)

Advisor: Todd Kahan

The visual processing system in the brain can be separated into the ventral or “what” pathway and the dorsal or “where/how” pathway. Researchers have used a technique known as Continuous Flash Suppression (CFS) in order to separate these pathways into two distinct regions. Under this tactic, the ventral stream is suppressed while the dorsal route is able to express activity and visually process a given stimulus. Further research on this topic has led to evidence showing that the dorsal stream has faster reaction times to negative human facial expressions than positive emotions (Yang et al., 2007). In addition, the capture of attention by negative stimuli may also occur for negative emotion-laden words. A study by Yang and Yeh (2010) found that negative words required a longer time to release from suppression than did neutral words.  The current experiment found that under CFS, participants took longer to detect negative words over positive and neutral words. However, in the control experiment, there was no significant difference in the time it took viewers to detect negative, positive, and neutral words. This supports that the discrepancy in reaction time is due to the CFS paradigm.

Investigation of an Opioid Antagonist on Rat Social Olfactory Memory

Curtis Gary Rheingold (Neuroscience)

Advisor: Jason Castro

Rat social interactions are mediated by pheromones—endogenous chemicals that convey unique information about each animal such as age, reproductive status, and social hierarchy. The accessory olfactory bulb (AOB) is the primary brain region involved in pheromonal processing. Several studies demonstrate that the AOB contains many types of opioid peptides and their receptors, but the role of opioidergic transmission in the AOB is not fully understood. Here I investigated the role of opioidergic neuromodulation in rat social olfactory memory. The opioid antagonist naloxone was directly injected into the AOB of male Wistar rats, and memory was assessed by the juvenile discrimination task. I found that naloxone administration is associated with diminished social recognition memory. These results suggest a role for endogenous opioids in mediating social olfactory memory formation, and further investigation is needed to better elucidate the mechanism by which opioids mediate social memory.

The Slope Relating Neural Frequency to Power and Attentional Control

Emily White (Neuroscience)

Advisor: Jesse J Bengson

The slope of the power spectrum of an electroencephalogram (EEG) reveals the presence of a 1/f1 relationship, as is often present in complex dynamic systems.  Although the deployment of attention has been shown to recruit large neuronal networks throughout the brain (Edelman, 2004), very little research has been conducted relating the spectral slope of the EEG to the deployment of attention. The present study uses an EEG data set recorded while subjects followed variants of a classic attentional cueing paradigm (Posner, 1980), to compare the slopes of the precue and postcue power spectra in the occipital lobe.  Compared to precue, the postcue spectral slope became significantly more negative in occipital regions contralateral to cue presentation. This is indicative of an increased amount of order in the visual cortex, or a lower possibility for information representation, with the deployment of anticipatory attention.