High-hostiles exhibit exaggerated physiological responses to stressors as seen by increased cardiovascular reactivity (BP & HR) (Rhodes, Harrison, & Demaree, 2002; Demaree & Harrison, 1997). This exaggerated physiological response style is associated with cardiovascular disease and premature death (Everson et al., 1997). This experiment hypothesized that diminished regulatory control would also be evident in the Acoustic Startle Response (ASR). In this experiment, high- and low-hostile undergraduate men (N = 40) were exposed to a series of startle probes before and after a cold pressor (CP). Startle responses were measured using electromyography (EMG) recorded over the orbicularis occuli. Cardiovascular measures of blood pressure and heart rate were also taken. A 2 X 2 mixed factorial ANOVA was performed with Group (high and low hostile) as the fixed factor, Condition (pre and post CP) as the repeated measure, and peak magnitude EMG (mV) of startle responses as the dependent variable. For startle responses, significant main effects for Group and Condition indicated that high hostiles had larger startle responses than low hostiles and startle responses decreased after the cold pressor (CP). A significant Group X Condition interaction effect was found. Post-hoc analyses revealed no significant group differences before the CP. After the CP, high-hostiles had significantly higher startle responses than-low hostiles. High-hostiles' startle responses did not change significantly after the CP, whereas low-hostiles' startle response magnitude decreased significantly after the CP. Low-hostiles HR increased significantly after the cold pressor and both groups SBP decreased significantly after the cold pressor. / Master of Science

Parvalbumin (PV) and cholecystokinin (CCK) proteins are found in the basolateral amygdala nuclei, particularly in gamma-aminobutyric acid (GABA) interneurons. PV+ neurons were localized to the basolateral amygdala and they expressed the GABA neuron marker glutamic acid decarboxylase (GAD). Here, we used Cre recombinase mouse lines to induce expression of mutant muscarinic inhibitory (hM4D) and excitatory (hM3D) receptors on PV+ or CCK+ neurons. Activation of the mutant receptors with clozapine-n-oxide (CNO) was used to measure how amygdala neural changes affect the acoustic startle reflex (ASR). Excitation of amygdala PV+ neurons potentiated the ASR. Activation of basolateral amygdalar CCK+ neurons potentiated the ASR and caused seizures, possibly by activating glutamate CCK+ neurons. The CCK+ subset of GAD neurons were targeted with a new triple transgenic mouse line (Dlx5-flpe/CCK-Cre/FrePe) to show that most CCK+ neurons were GAD negative. These findings are compared with optogenetic approaches to target specific neuronal populations.

Parvalbumin (PV) and cholecystokinin (CCK) proteins are found in the basolateral amygdala nuclei, particularly in gamma-aminobutyric acid (GABA) interneurons. PV+ neurons were localized to the basolateral amygdala and they expressed the GABA neuron marker glutamic acid decarboxylase (GAD). Here, we used Cre recombinase mouse lines to induce expression of mutant muscarinic inhibitory (hM4D) and excitatory (hM3D) receptors on PV+ or CCK+ neurons. Activation of the mutant receptors with clozapine-n-oxide (CNO) was used to measure how amygdala neural changes affect the acoustic startle reflex (ASR). Excitation of amygdala PV+ neurons potentiated the ASR. Activation of basolateral amygdalar CCK+ neurons potentiated the ASR and caused seizures, possibly by activating glutamate CCK+ neurons. The CCK+ subset of GAD neurons were targeted with a new triple transgenic mouse line (Dlx5-flpe/CCK-Cre/FrePe) to show that most CCK+ neurons were GAD negative. These findings are compared with optogenetic approaches to target specific neuronal populations.

This study examined the effects of genetic background on the acoustic startle response (ASR) and its modulation by prepulse inhibition (PPI) by comparing nine inbred strains of mice. The ASR, a jerk-like motor reflex, is elicited by bursts of noise or tones with sound pressure levels of 80-90 dB and greater. PPI is a type of modulation of the ASR, requires no training, and results in observable response in both mice and humans. Data were obtained from nine inbred mouse strains, sixteen per strain, which were shipped at approximately 3-5 weeks old from The Jackson Laboratory. In general, ASRs were generally smaller when the startle stimulus was less intense. PPI was relatively weak for the 4 kHz prepulse, and stronger with prepulses of 12 kHz and 20 kHz. However, means varied widely across strains for both ASR and PPI, suggesting a strong influence of genetic background on these behaviors. In addition to genetic influences, peripheral hearing loss and central auditory processing factors must be taken into consideration.

A lack of empathy is considered to be a hallmark feature of psychopathy. However, remarkably little research has specifically examined the relationship between psychopathy and empathy, and what does exist relies solely on self-report measures, which is problematic given psychopaths' propensity for dishonesty. This research signifies an attempt to develop an objective measure of empathy, using psychophysiological indices of emotional experience as indicators of an empathic response. Specifically, corrugator and zygomatic facial muscle activity, event-related heart rate, and acoustic startle reflex responses were measured while participants viewed brief films of individuals experiencing happy and sad emotional events.Pilot investigations of the films suggest they are appropriate for eliciting happy and sad empathic emotion, and the pattern of responses by undergraduates with high and low trait levels of empathy indicates the validity of the approach, and the promise of utilizing psychophysiological indices of emotional responding to measure situational empathy in an objective manner. In particular, participants demonstrated patterns of psychophysiological responses to the empathy-inducing films which both matched their self-reported emotional experiences as well as the emotional valence of the stimuli. Moreover, several of the psychophysiological indices were able to discriminate high and low empathy individuals, whereby low empathy participants exhibited less facial expressiveness and less modulation of the acoustic startle reflex to the empathy-inducing stimuli than their high empathy counterparts.The paradigm was then extended to a sample of male undergraduates with high and low levels of psychopathic traits, as assessed by the Psychopathic Personality Inventory-Revised. Results suggest a significant negative relationship between self-reported psychopathy and self-reported dispositional empathy, with high levels of psychopathy associated with low levels of dispositional empathy, particularly with respect to affective empathy. However, despite differences in dispositional empathy, psychopathic and non-psychopathic undergraduates were not easily discriminated on subjective or objective measures of situational empathy, with the exception of an anomalous pattern of zygomatic EMG activity exhibited by the psychopathic participants. The implications of these findings are discussed with respect to the nature of the empathic capabilities of psychopaths, as well as considerations of the methodological limitations of the current study and directions for future research.

N-methyl-D-asparate (NMDA) receptors located within the basolateral complex of the amygdala are required for the consolidation and expression of Pavlovian conditioned fear. The events downstream of receptor activation that mediate these processes are not well defined. An intermediate step that may be of significance is the synthesis of the gas nitric oxide (NO). Nitric oxide is synthesised as a result of NMDA receptor activation and acts as an unconventional neurotransmitter freely diffusing across cell membranes interacting with its targets in a non-synaptic manner. The targets of NO include cellular components that play significant roles during the consolidation of conditioned fear and the neurotransmission associated with its expression. This implies that NO may be an important intermediary of NMDA receptor activation and both these processes. The current study sought to examine this possibility using fear potentiated startle to examine the expression of learned fear. Three experiments were conducted, fifty rats received intra-BSC microinfusions of the global nitric oxide synthase inhibitor L-NAME either prior to fear conditioning, fear testing, or examination of the shock sensitization of the acoustic startle affect. The results indicated that NO was indeed required for both the consolidation and expression of learned fear, whereas it was not required for shock enhanced startle responding. This study provides new information about the sub-cellular basis of conditioned fear, and highlights the pivotal role played by NO in processes associated with conditioned fear.

Millions of people suffer from tinnitus, a disorder for which there is currently no effective treatment or cure. My dissertation work provides insight into the neural correlates of this pervasive hearing disorder and examines how a newly emerging therapy, transcranial magnetic stimulation (TMS), affects the central auditory system in the generation of the tinnitus percept. This work has a multifold focus of: i) developing and modeling the function of a miniature magnetic coil that can be used for TMS in rodents, ii) establishing a reliable mouse model of tinnitus that can be used for assessing TMS treatment-induced changes, iii) measuring the behavioral alterations and neural changes induced by TMS throughout the auditory system in mice with tinnitus, and iv) to assay underling molecular changes in the auditory cortex (AC) related to TMS and tinnitus. Chapter 1 gives an overview of the current research on tinnitus and TMS. Chapter 2 establishes a reliable neural and behavioral assay of verifying tinnitus in a mouse model and provides further evidence that the underlying hyperactivity associated with tinnitus is initiated in the brainstem following reduced afferent input. The remainder of the dissertation examines the modulation of tinnitus in the auditory central nervous system using a miniature TMS coil. Chapter 3 of the dissertation details the creation and evaluation of a rodent-sized TMS coil, which could increase the overall effectiveness and applicability for human treatment. TMS is currently an FDA approved treatment of depression and has been shown to decrease tinnitus perception in human clinical trials, albeit with variable results. There have been few published studies of tinnitus modulation by TMS using animal models and therefore little is known about the molecular and neural bases of this potential tinnitus treatment. TMS is thought to be therapeutic because the magnetic flux generated from the electromagnetic coil induces an electric field in the brain, altering ion flow and subsequently neural function, as the excitation and inhibition of cortical networks become synchronized to the magnetic pulse. Chapter 4 demonstrates that TMS with our custom-designed miniature rodent coil can successfully reduce behavioral evidence of tinnitus in a mouse model, mainly through activating inhibitory networks in the AC. It also shows that presynaptic activity is altered in the upper layers of the AC responsible for intralaminar processing and sound perception. Finally, chapter 5 describes an in-depth proteomic analysis of over 3000 proteins from the AC, which shows that TMS and noise-induced tinnitus alter the expression of several key proteins and pathways that play a critical role in cortical excitatory and inhibitory activation. The results of this work are also important because they are the first animal model to demonstrate neural changes during TMS-treated tinnitus, creating a paradigm that can be used for optimizing parameters to improve clinical outcomes in human trials.

N-methyl-D-asparate (NMDA) receptors located within the basolateral complex of the amygdala are required for the consolidation and expression of Pavlovian conditioned fear. The events downstream of receptor activation that mediate these processes are not well defined. An intermediate step that may be of significance is the synthesis of the gas nitric oxide (NO). Nitric oxide is synthesised as a result of NMDA receptor activation and acts as an unconventional neurotransmitter freely diffusing across cell membranes interacting with its targets in a non-synaptic manner. The targets of NO include cellular components that play significant roles during the consolidation of conditioned fear and the neurotransmission associated with its expression. This implies that NO may be an important intermediary of NMDA receptor activation and both these processes. The current study sought to examine this possibility using fear potentiated startle to examine the expression of learned fear. Three experiments were conducted, fifty rats received intra-BSC microinfusions of the global nitric oxide synthase inhibitor L-NAME either prior to fear conditioning, fear testing, or examination of the shock sensitization of the acoustic startle affect. The results indicated that NO was indeed required for both the consolidation and expression of learned fear, whereas it was not required for shock enhanced startle responding. This study provides new information about the sub-cellular basis of conditioned fear, and highlights the pivotal role played by NO in processes associated with conditioned fear.

Toxoplasma gondii infection is common in humans and is a significant risk factor for developing the disease schizophrenia. Genetic risk factors are likely required for the disease of schizophrenia to develop. Nurr1 – heterozygous (+/-) mice and wild-type (+/+) mice were evaluated using immune activation of astrocytes within the prefrontal cortex, dopamine levels within the striatum, and measuring the acoustic startle response reaction time by using prepulse inhibition (PPI). T. gondii infected heterozygous (+/-) mice exhibited increased GFAP expression within the prefrontal cortex. Dopamine levels within the striatum were measured and T. gondii infected wild-type (+/+) mice exhibited increased dopamine levels. The acoustic startle response reaction time was measured using PPI and T. gondii infected mice exhibited slower reaction times when compared to controls. These data demonstrate that the Nurr1 (+/-) genotype predisposes mice to T. gondii-induced alterations in behaviors that involve dopamine neurotransmission and are associated with symptoms of schizophrenia.

Title from PDF of title page. / Document formatted into pages; contains 18 pages. / Thesis (Au.D.)--University of South Florida, 2003. / Includes bibliographical references. / Text (Electronic thesis) in PDF format. / ABSTRACT: This study examined the effects of genetic background on the acoustic startle response (ASR) and its modulation by prepulse inhibition (PPI) by comparing nine inbred strains of mice. The ASR, a jerk-like motor reflex, is elicited by bursts of noise or tones with sound pressure levels of 80-90 dB and greater. PPI is a type of modulation of the ASR, requires no training, and results in observable response in both mice and humans. Data were obtained from nine inbred mouse strains, sixteen per strain, which were shipped at approximately 3-5 weeks old from The Jackson Laboratory. In general, ASRs were generally smaller when the startle stimulus was less intense. PPI was relatively weak for the 4 kHz prepulse, and stronger with prepulses of 12 kHz and 20 kHz. However, means varied widely across strains for both ASR and PPI, suggesting a strong influence of genetic background on these behaviors. / ABSTRACT: In addition to genetic influences, peripheral hearing loss and central auditory processing factors must be taken into consideration. / System requirements: World Wide Web browser and PDF reader. / Mode of access: World Wide Web.