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This study assessed the in vivo effects of various serotonin (5-HT) receptor modulators on 5-HT neurotransmission in the rat hippocampus. Vortioxetine, humanized-vortioxetine, and escitalopram blocked the 5-HT transporter, but similar to ipsapirone did not dampen the sensitivity of postsynaptic 5-HT1A receptors. Long-term administration of all treatments increased the tonic activation of postsynaptic 5-HT1A heteroreceptors, an effect common to all antidepressants. Vortioxetine decreased the function of the terminal 5-HT1B autoreceptor under high but not a low degree of activation, thus showing that its partial agonism led to increased 5-HT release and that long-term administration results in the desensitization of terminal 5-HT1B autoreceptors. Vortioxetine overcame the effects of 5-HT1B and 5-HT3 receptor agonists. This study was unable to determine the involvement of 5-HT7 receptor antagonism exerted by vortioxetine affects 5-HT neurotransmission. Therefore, vortioxetine would appear to exert different actions, via transporter and receptor activity, on the serotonergic system in the hippocampus, consistent with its unique pharmacological profile.

The brain is protected by the blood brain barrier (BBB); areas lacking the BBB are termed circumventricular organs (CVOs). The SFO, a CVO is capable of detecting and responding to satiety signals that regulate energy balance. Insulin, a satiety signal, plays a role in energy balance and its actions at the SFO are unknown. The goal was to determine if cultured SFO neurons are electrophysiologically sensitive to insulin. Of 27 neurons tested 33% neurons hyperpolarized (-8.7 ± 1.7 mV), 37% neurons depolarized (10.5 ±2.8 mV) and 30% neurons (8 out of 27) showed no change in membrane potential. Input resistance changes indicated the modulation of two ion channels. Pharmacological data suggests hyperpolarization arises from the opening of KATP channels and depolarization results from the opening of non-selective cationic channels. Thus insulin modulates the electrical activity of SFO neurons and supports that the SFO is a sensor for maintaining energy homeostasis.

<p>Any information represented in the brain, whether an individual is aware of it or not, holds the potential to affect behavior. The extent of visual perceptual processing that occurs in the absence of awareness is therefore a question of broad import and interest to the field of cognitive neuroscience. A useful approach for examining the extent and quality of visual processing that occurs in the absence of awareness is the dissociation paradigm. In this approach, experimenters track implicit measures of the visual process of interest across conditions of awareness modulated by visual presentation manipulations. Object-category discrimination by the visual system represents a relatively sophisticated level of representation that may or may not occur in the absence of awareness. Here, electrophysiological measures (scalp-recorded event-related potentials, or ERPs) of object-category discrimination by the brain (the face-specific N170 ERP component and the longer-latency face-specific negativity) were tracked across conditions of visual awareness as manipulated by multiple presentation paradigms (sandwich masking, object-substitution masking, the attentional blink, and motion-induced blindness). In addition, where possible, other related comparisons examining lower-level visual processes and higher-level attentional processes were employed to help delineate the specific level and mechanism by which awareness was disrupted in each case. The experiments implicated a unique set of mechanisms of reducing awareness for each method, while providing insight into the complex relationships between the various phases of visual processing in the human brain and awareness. Ultimately it was observed that neural indices of face-specific processing are differentially susceptible to disruption exerted by these various methods, and that there do in fact exist conditions in which awareness can be disrupted while leaving various facets and phases of face-specific processing intact. These findings help to establish object-category discrimination as a process that can occur in the absence of visual awareness, and contributes to our understanding of the neural factors that influence and determine behavior.</p> / Dissertation

The experiments in this thesis used behavioural measures and event-related potentials (ERPs) to investigate the influence of race on face processing in the brain. Previous behavioural research has highlighted an own-race effect in face processing, whereby individuals are more accurate at recognizing own-race compared to other-race faces. The current Thesis examined the own-race effect at perceptual and neural levels. Social influences on the own-race effect were also investigated, such as other-race experience, anxiety and implicit social bias, as these may account for differential own- versus other-race face processing. The main aim of the experiments contained in this thesis was to delve deeper into the examination of own and other-race face perception through a series of original experiments. Participants performed a variety of perceptual discrimination and identification tasks, and completed measures of explicit other-race experience and implicit racial bias to record their perceptions of other-race individuals. Chapters 2-4 saw the development of a new paradigm that tested the own-race effect in perception, in contrast to traditional recognition memory investigations. In Chapter 2 the own-race effect was investigated developmentally and found across three age-groups, and was larger in the two older age-groups. Chapters 3 and 4 found that the own-race effect differed across racial groups, and that social variables such as other-race experience influenced the strength of the own-race effect. In the latter experimental chapters, ERPs revealed that the behavioural own-race effect was evident at a neural level. Chapter 7 demonstrated that face-related stages of processing in the brain were sensitive to race of face. In Chapters 8 and 9, the sensitivity of face processing to own and other-race emotional expression processing was also examined. The additional social factor of emotional expression was explored in order to further the investigation of socially relevant information processing from the face. Findings from the last two experimental chapters demonstrated differential emotional face processing for own- versus other-race faces. Confirming the findings of the behavioural experiments, own- versus other-race emotion processing varied across racial groups and was subject to social influences such as other-race experience, intergroup anxiety and implicit racial bias. Overall, behavioural and neural investigations of the own-race effect demonstrated the influence of social variables such as other-race experience, intergroup anxiety and implicit racial bias on the way in which individuals processed own- versus other-race faces in the human brain.

This dissertation explores the neural coding and mechanisms associated with consciousness by analyzing electrical rhythms of the brain under altered states of consciousness, namely epilepsy and anesthesia. First, transformation of neural coding under epileptogenic conditions is examined by computing the Volterra kernels in a rodent epilepsy model, where the epileptogenic condition is induced by altering the concentrations of Mg2+ and K+ of the perfusate for different levels of excitability. Principal dynamic modes (PDMs) are further deduced from the Volterra kernels to compare the changes in neural dynamics under epileptogenic conditions. The integrating PDMs are shown to dominate at all levels of excitability in terms of their relative contributions to the overall response, whereas the dominant frequency responses of the differentiating PDMs shift to higher ranges under epileptogenic conditions, from ripple activities (75 - 200 Hz) to fast ripple activities (200 - 500 Hz). Second, markers of anesthetic states are explored by analyzing amplitude and phase of brain rhythms as well as their interaction and modulation, utilizing electroencephalogram (EEG) recorded from patients undergoing anesthesia. Anesthesia shifts the power to low frequency rhythms, especially alpha rhythms. Additionally anesthesia increases the coupling between alpha rhythms and gamma rhythms while disrupting the coupling between alpha rhythms and ripples (70 - 200 Hz). The results also indicate that the dose responses (i.e. depth of anesthesia) are not necessarily monophasic or linear. The commonality and differences of the changes in brain rhythms associated with these conditions are discussed to elucidate on the possible underlying mechanisms involved in producing consciousness.

There is a large sex difference in the prevalence of attention deficit disorder; yet, little is known about sex differences in prefrontal attention circuitry. We investigated sex differences in the developmental nicotinic excitation of corticothalamic layer VI neurons, which play an important role in attention. Using whole cell recording in prefrontal brain slices, we examined the inward currents elicited by nicotinic stimulation in rodents. We found a prominent sex difference in the currents during the first postnatal month when males had significantly greater α4β2* nicotinic currents. Immunohistochemical analysis of α4YFP mice revealed no sex difference in the pattern or proportion of YFP-positive neurons in layer VI. Further electrophysiological experiments revealed that progesterone is able to rapidly and significantly suppress nicotinic currents in layer VI neurons. This is the first illustration at a cellular level that prefrontal attention circuitry is differently excited by nicotinic stimulation in males and females during development.

This dissertation explores the neural coding and mechanisms associated with consciousness by analyzing electrical rhythms of the brain under altered states of consciousness, namely epilepsy and anesthesia. First, transformation of neural coding under epileptogenic conditions is examined by computing the Volterra kernels in a rodent epilepsy model, where the epileptogenic condition is induced by altering the concentrations of Mg2+ and K+ of the perfusate for different levels of excitability. Principal dynamic modes (PDMs) are further deduced from the Volterra kernels to compare the changes in neural dynamics under epileptogenic conditions. The integrating PDMs are shown to dominate at all levels of excitability in terms of their relative contributions to the overall response, whereas the dominant frequency responses of the differentiating PDMs shift to higher ranges under epileptogenic conditions, from ripple activities (75 - 200 Hz) to fast ripple activities (200 - 500 Hz). Second, markers of anesthetic states are explored by analyzing amplitude and phase of brain rhythms as well as their interaction and modulation, utilizing electroencephalogram (EEG) recorded from patients undergoing anesthesia. Anesthesia shifts the power to low frequency rhythms, especially alpha rhythms. Additionally anesthesia increases the coupling between alpha rhythms and gamma rhythms while disrupting the coupling between alpha rhythms and ripples (70 - 200 Hz). The results also indicate that the dose responses (i.e. depth of anesthesia) are not necessarily monophasic or linear. The commonality and differences of the changes in brain rhythms associated with these conditions are discussed to elucidate on the possible underlying mechanisms involved in producing consciousness.

There is a large sex difference in the prevalence of attention deficit disorder; yet, little is known about sex differences in prefrontal attention circuitry. We investigated sex differences in the developmental nicotinic excitation of corticothalamic layer VI neurons, which play an important role in attention. Using whole cell recording in prefrontal brain slices, we examined the inward currents elicited by nicotinic stimulation in rodents. We found a prominent sex difference in the currents during the first postnatal month when males had significantly greater α4β2* nicotinic currents. Immunohistochemical analysis of α4YFP mice revealed no sex difference in the pattern or proportion of YFP-positive neurons in layer VI. Further electrophysiological experiments revealed that progesterone is able to rapidly and significantly suppress nicotinic currents in layer VI neurons. This is the first illustration at a cellular level that prefrontal attention circuitry is differently excited by nicotinic stimulation in males and females during development.

Introduction: Psychophysical and electrophysiological techniques have shown that chromatic contrast sensitivity improves between infancy and adolescence. In adults, electrophysiological and psychophysical methods usually agree. However, in infants electrophysiological techniques may underestimate ability to see chromatic contrast (Suttle et al., 2002). It is not known if the discrepancy between electrophysiological and psychophysical methods continues during childhood nor whether the chromatic VEP can be used as an indicator of colour perception in children. Purpose: To investigate the transient L-M chromatic visual evoked potential and its ability to indicate perception (psychophysical thresholds) of chromatic stimuli in children and adults. In particular, to determine whether a discrepancy between VEP and psychophysical L-M thresholds exists during childhood and if so, to gain some understanding about the nature of the discrepancy. Methods: Transient chromatic VEPs were recorded in children (aged 4.5-13 years) and adults (aged 20-40 years). VEP thresholds were compared with psychophysical thresholds (within-subjects comparison). Because the VEPs of the children were less intra-individually repeatable in morphology than those of the adults, post-hoc objective analysis of the VEPs, linear (Fourier) and nonlinear dynamical (Grassberger and Procaccia's (1983) correlation dimension) analyses, was conducted. Results: VEP and psychophysical estimates of chromatic contrast thresholds agreed using a variety of methods in the adults. In the children, however, the objective methods of assessment (extrapolation from Fourier-derived amplitudes and the correlation dimension) were more accurate than the methods that employed subjective evaluations of VEP morphology. Conclusion: The L-M transient chromatic VEPs of both children (aged 4.5-13 years) and adults appear to contain chromatic information, even in the absence of repeatable VEP morphology and should therefore be able to indicate chromatic perception (psychophysical thresholds). However, the chromatic information may be present as a nonlinear dynamical signal, which may require objective methods (Fourier analysis, the correlation dimension) to reveal the chromatic signal. The greater intra-individual variability of VEP morphology in children compared to adults may reflect poorer precision when switching between cortical states in children's brains. Alternatively, interactions between the immature visual system of the children and their general EEG may occur. Children's VEPs should therefore be interpreted differently to adult VEPs.