The amygdala, a small structure located deep bilaterally in the medial temporal lobe, is the key structure for the emotional processing and storage of memories associated with emotional events, especially fear. The structure has also been shown to enable humans and animals to detect and respond to environmental threats. Fear conditioning became the main model to examine the neural substrates of emotional learning in mammals and specifically in rats’. With the fear conditioning method, researchers can tests rats’, responses to aversive stimuli during the delivery of a cue and then measure how the responses change after learning of the association between the stimuli and the cue. After learning of the two stimuli, the delivery of a cue alone will prompt a fear response in the rats. The fear response can also be elicited by placing the rats in the same chamber in which the aversive stimuli has previously been experienced, which depends on both the amygdala and the hippocampus. Where the amygdala stores the memories of stimulus related to fear, the hippocampus seems to hold all the fear memories in relation to contextual information about the stimulus. The aim of this paper will be to make a comprehensive overview of internal neural processes of both the amygdala and hippocampus and the interaction between the two structures during fear conditioning, to see how the structures separately work to overlap emotion and memory processes.

GABAergic interneurons in the basolateral complex (BLC) of the amygdala are a part of the emotional-learning circuitry of the brain and receive excitatory inputs from all sensory modalities via cortex and thalamus. Although the BLC, which is made up of the lateral amygdala (LA), basal amygdala (BA) and accessory basal nucleus, is under the influence of a strong inhibition brought about by local interneurons, little is known about the diversity, characteristics and functioning of these interneurons. In this study, I have characterised the BLC interneuron population using a transgenic mouse model in which enhanced green fluorescent protein has been tagged to the GAD67 promoter. This promoter is specifically expressed in all GABAergic interneurons, enabling us to visualise interneurons under UV light. Whole-cell recordings were made from GAD67 interneurons in the BLA to study their membrane and synaptic properties. On the basis of their firing properties, interneurons in the BLC were classified into six distinct groups. The calcium-binding proteins calbindin, calretinin and parvalbumin were found to be expressed differently in the LA and BA interneurons, with the majority of the interneurons in the LA expressing calretinin, whereas those in the BA mostly expressed parvalbumin. We also found diversity in the expression of postsynaptic glutamate receptors in the BLC. Long-term potentiation induced at the interneurons was specific to the cortical inputs in the LA. LTP was expressed only in interneurons that either lacked NMDA receptors or had NMDA receptors with fast decay kinetics. This form of LTP was mediated by calcium-permeable AMPA receptors and required a postsynaptic calcium rise for its induction This study shows that the interneurons in the BLC are a heterogenous population with respect to the expression of calcium-binding proteins, axonal morphology, synaptic and membrane properties. This heterogeneity in interneuron population may be essential for the specialised roles various types of interneurons play in the functioning of the amygdala and in emotional learning.

Thesis (Ph. D.)--University of Oklahoma. / Includes bibliographical references.

Orientador: Donizeti Cesar Honorato / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T11:34:40Z (GMT). No. of bitstreams: 1 Veronez_DjaniraAparecidadaLuz_D.pdf: 1713916 bytes, checksum: 0bb9082c7d06dda2f3716d4715c53cd9 (MD5) Previous issue date: 2006 / Resumo: A epilepsia do lobo temporal (ELT) apresenta-se em um percentual elevado de pacientes que são refTatários ao tratamento clínico. Fato este que faz da ELT a epilepsia que melhor responde ao tratamento cirúrgico baseado na lobectomia do lobo temporal e na amígdalo-hipocampectomia. Esta última técnica cirúrgica consiste na ressecção parcial do corpo amigdalóide, do hipocampo e do giro para-hipocampal; estruturas consideradas epileptogênicas. Destas estruturas, o corpo amigdalóide é o único ainda com volume morfológico e morfométrico indeterminado. Com base nestes fatos, este trabalho apresenta como objetivos, determinar em cérebros de cadáveres humanos, parâmetros quantitativos e tridimensionais do corpo amigdalóide a partir da análise de cortes bidimensionais; definir os limites topográficos macroscópicos do corpo amigdalóide; estabelecer as distâncias entre o como temporal do ventrículo lateral e as superficies utilizadas nos acessos cirúrgicos; expressar os resultados em escalas métricas, da análise morfométrica e estereológica e sugerir o uso destas nas amígdalo-hipocampectomias. Para isto realizamos análise de cortes seriados, coronais e parassagitais do corpo amigdalóide, que foram avaliados através de um sistema de processamento e análise de imagem. O método de Cavalieri foi utilizado para estabelecer o volume absoluto do corpo amigdalóide. Por último, foram feitas análises estatísticas e apresentação gráfica dos resultados. Os hemisférios cerebrais, direitos e esquerdos foram analisados separadamente, para verificar a morfometria do corpo amigdalóide. Foram observadas diferenças inter-hemisféricas na volumetria do corpo amigdalóide. Nos cortes coronais a média do volume absoluto do corpo amigdalóide direito foi de 1.870mm3 e do corpo amigdalóide esquerdo foi de 1.807mm3, com índice de assimetria de 3,4%. Nos cortes parassagitais a média do volume absoluto do corpo amigdalóide direito foi de 1.927mm3 e do corpo amigdalóide esquerdo foi de 1.878mm3, com índice de assimetria de 2,6%. Não foi identificada variabilidade anatômica significativa na topografia dos ventrículos laterais e do corpo amigdalóide. Nossos resultados demonstram que a análise morfométrica e estereológica aplicada ao corpo amigdalóide e as medidas obtidas na topografia do lobo temporal constitui instrumento confiável, que pode auxiliar nas cirurgias de amígdalo-hipocampectomias / Abstract: The temporallobe epilepsy (TLE) has a high percentage of patients who are reffactory to a clinical treatment. This fact makes TLE the epilepsy that best responds to a surgi cal treatment. It is based on lobectomy of temporallobe and on amygdalohippocampectomy. This surgi cal technique consists of a partial resection of the amygdaloid complex, hippocampus, and gyrus parahippocampal. These structures are considered as epileptogenics. Among these structures, the amygdaloid complex is the only with undetermined morphological and morphometric volume. Based on these facts, this study will have the following objectives: to determine in brains of human corpses the quantitative and three-dimensional parameters of the amygdaloid complex obtained ITom analyses of two-dimensional slices; to define the topographic macroscopic limits of the amygdaloid complex; to establish the distances between the temporal hom of the lateral ventricles and the surfaces used for the surgi cal approaches; to express the results in metrical scales of morphometric and estereological analysis of the amygdaloid complex, and to suggest the use of them in an amygdalohippocampectomy. In order to do this, we have accomplished analysis of serial, coronary and parasagital slices of the amygdaloid complex, which were evaluated through a processing system and an image analysis. The Cavalieri Method was used to establish the absolute volume of the amygdaloid complexo Finally, estatistics analyses and a graphical presentation of the results were done. Right and left brain hemispheres were analyzed separately in order to verify the morphometry of the amygdaloid complexo The inter-hemispherical differences in the volumetry of the amygdaloid complex were observed. In the coronal slices the absolute medium volume of the right amygdaloid complex was 1.894mm3, and the left was 1.837mm3 with an index of asymmetry of 3,4%. In the parassagital si ices the absolute medium volume of the right amygdaloid complex was of 1.927mm3 and the left amygdaloid complex was 1.878mm3 with an index of asymmetry of 2,6%. We have verified that there was no significant anatomical variation in the topography of lateral ventricles and the amygdaloid complexo Our results demonstrate that a morphometric and estereological analysis applied to the amygdaloid complex and measurements obtained in the topography of the temporallobe is a reliable instrument, which can help in surgeries ofthe amygdalohippocampectomy / Doutorado / Ciencias Biomedicas / Doutor em Ciências Médicas

Autism spectrum disorder (ASD) is a complex disorder with large individual variability, where every case has differences in the type and severity of symptoms. Despite the recent increase in diagnoses, scientists have advanced considerably less in their understanding of the mechanisms of ASD because few individual genes that are implicated in ASD are mutated in much more than 1% of patients. One proposed mechanism is that the dysfunction of GABAergic interneurons may play a role in the development and progression of the disorder by interrupting the excitatory and inhibitory balance of neural networks. In our research, we elucidate the role of one class of interneurons in ASD by knocking out a high-risk gene (phosphatase and tensin homologue on chromosome ten, or PTEN) selectively in somatostatinexpressing (SOM+) interneurons. Since many symptoms of autism spectrum disorder present themselves as social anxieties, we test our mouse model in a variety of settings to observe social interaction and social preference, anxiety-like behavior, and repetitive stereotyped behavior. We found that in the SOM+ conditional knockout of PTEN, mice had elevated levels of anxiety and fear recall, suggesting a potential disruption of amygdala function. We then investigated potential dysfunction at the cellular and circuit levels using confocal microscopy, electrophysiology, and 2P local circuit mapping. We found that SOM+ cells lacking PTEN were overgrown morphologically, with larger cell bodies and larger, more complex dendritic arbors. Additionally, SOM+ cells in the central amygdala (CeA) lacking PTEN had elevated levels of excitatory drive from the basolateral amygdala (BLA) as well as a drastic disruption of lateral inhibition within the CeA, seen by decreased connection probability and reduced inhibitory post synaptic currents. Given what is known about central amygdala circuitry, these deficits in CeA SOM+ neuron activity conceivably underlie the fear and anxiety-related phenotype observed in mice with a conditional SOM+ PTEN knockout. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2021. / FAU Electronic Theses and Dissertations Collection

Indiana University-Purdue University Indianapolis (IUPUI) / The GABRA2 gene, which encodes the α2 subunit of GABAA receptors, is one of the genes most frequently associated with alcohol-related behavior in human studies (Demers, Bogdan, & Agrawal, 2014). Polymorphisms in GABRA2 have been found to be associated with alcohol dependence, changes in drinking frequency, and alcohol’s stimulating and euphoric effects (Arias et al., 2014; Dick et al., 2014; Edenberg et al., 2004). However, the GABRA2-alcohol relationship may not be direct, as anxiety and impulsiveness have been found to be mediating factors (Enoch, Schwartz, Albaugh, Virkkunen, & Goldman, 2006; Villafuerte, Strumba, Stoltenberg, Zucker, & Burmeister, 2013). Comorbidity of anxiety and alcohol use disorders is both prevalent and clinically relevant (J. P. Smith & Randall, 2012), and GABAA receptors play a significant role in each. Benzodiazepines, primary pharmacologic treatments for anxiety disorders and alcohol withdrawal, facilitate signaling at GABAA receptors, and their anxiolytic effects appear to depend on the presence of α2 subunits in these receptors (Low et al., 2000). The amygdala is widely implicated in both anxiety disorders as well as addiction (Janak & Tye, 2015), and its central nucleus is an important mediator of responses to both alcohol- and stress-related stimuli (Roberto, Gilpin, & Siggins, 2012), some of which may be related to GABRA2 expression within this region (Jin et al., 2014). The aim of the current study was to explore the role of Gabra2 (mouse ortholog of GABRA2) expression within the central nucleus of the amygdala (CeA) in anxiety-related behavior and alcohol’s anxiolytic effects in mice. C57BL/6J (B6) mice underwent surgery for bilateral infusion of GFP-tagged lentivirus targeting Gabra2 or a scramble control lentivirus into the CeA. Following 12-13 days of recovery, mice were assessed for anxiety-like behavior in the elevated plus maze (EPM) naïve or following IP injection of 0, 0.75, or 1.5 g/kg ethanol. After assessment, brains were extracted and sectioned through the CeA. Finally, GFP was quantified, the CeA was collected via laser microdissection, and α2 protein was quantified via ELISA. In mice expressing GFP in the CeA, α2 protein concentrations were lower for Virus mice relative to Control mice. The EPM was anxiogenic, and alcohol was found to be anxiolytic. In naïve mice, while there was no difference between Control mice and Virus mice on any behavioral measure, there were significant correlations between CeA α2 protein concentration and time spent in closed arms as well as both total and average time spent in open arms. In mice receiving injection of 0, 0.75, or 1.5 g/kg ethanol, there was a main effect of dose on several behavioral measures, but no interaction between viral condition and dose, and only a main effect of viral condition on average time spent in closed arms. There were no significant correlations between CeA α2 protein concentration and behavioral measures within any injected dose. These results are consistent with GABRA2-anxiety associations and effects of Gabra2 manipulation on anxiety-like behavior. Furthermore, they suggest that CeA α2 protein concentration is positively related to basal anxiety, which could affect alcohol use through various routes. However, these results also suggest that CeA α2 protein concentration is not related to alcohol’s anxiolytic capacity, at least when acutely administered in alcohol-naïve animals.

Music is a powerful and reliable means to stimulate the percept of both intense pleasantness and unpleasantness in the perceiver. However, everyone’s social experiences with music suggest that the same music piece may elicit a very different valence percept in different individuals. A comparison of music from different historical periods suggests that enculturation modulates the valence percept of intervals and harmonies, and thus possibly also of relatively basic feature extraction processes. Strikingly, it is still largely unknown how much the valence percept is dependent on physical properties of the stimulus and thus mediated by a universal perceptual mechanism, and how much it is dependent on cultural imprinting. The current thesis investigates the neurophysiology of the valence percept, and the modulating influence of culture on several distinguishable sub-processes of music processing, so-called functional modules of music processing, engaged in the mediation of the valence percept. / Musik eignet sich besonders gut, um sowohl intensive Angenehmheit/Lust und Unangenehmheit/Unlust (siehe auch Wundt, 1896), so genannte Valenzperzepte, im Zuhörer hervorzurufen. Jedoch kann derselbe musikalische Stimulus sehr unterschiedliche Valenzperzepte in verschiedenen Zuhörern hervorrufen, was nahe legt, dass das durch Musik vermittelte Valenzperzept zumindest teilweise durch kulturelle Prägung moduliert wird. Ein Vergleich von Musik verschiedener historischer Perioden legt ebenfalls nahe, dass kulturelle Prägung das Valenzperzept des Hörers bei der Wahrnehmung von Intervallen und Harmonien moduliert. Wichtigerweise ist es nach wie vor weitgehend unbekannt, inwiefern das Valenzperzept von physikalischen Eigenschaften des Stimulus (z.B. Rauhigkeit) abhängt - und daher auf einem universellen perzeptiven Mechanismus basiert - oder wie sehr es abhängt von kultureller Prägung. Die vorliegende Dissertation untersucht die Neurophysiologie des Valenzperzepts, sowie den modulierenden Einfluss von Kultur auf mehrere funktionelle Module der Musikwahrnehmung (voneinander unterscheidbare Subprozesse der Musikwahrnehmung), die bei der Entstehung des Valenzperzepts beteiligt sind.

Adaptive reproductive behavior requires the ability to recognize and approach possible mating partners in the environment. Syrian hamsters (Mesocricetus auratus) provide a useful animal model by which to study the neural processing of sexual signals, as mate recognition in this species relies almost exclusively on the perception of social odors. In the laboratory, male hamsters prefer to investigate female odors compared to male odors, and this opposite-sex odor preference provides a sensitive measure of the underlying neural processing of sexual stimuli. In addition to chemosensory cues, reproductive behavior in hamsters also requires sufficient levels of circulating gonadal steroid hormones, which reflect the reproductive state of the animal. These chemosensory and hormone signals are processed within an interconnected network of ventral forebrain nuclei, and within this network, the posteromedial cortical amygdala (PMCo) and medial amygdala (MA) are the only nuclei that both receive substantial chemosensory input and are also highly sensitive to steroid hormones. Although a large body of evidence suggests that the MA is critical for generating attraction to sexual odors, the specific role of the PMCo in regulating odor-guided aspects of male reproductive behavior has never been directly tested. Furthermore, detailed analyses of the MA suggest that separate, but interconnected sub-regions within this nucleus process odors differently. Specifically, the anterior MA (MeA) receives the majority of chemosensory input and responds to a variety of social odors, whereas the posterodorsal MA (MePD) receives less chemosensory input but contains the vast majority of steroid receptors. In order to further elucidate how the PMCo and/or MA process sexual odors, this dissertation addressed the following research questions: (1) Is the PMCo required for the expression of either opposite-sex odor preferences or male copulatory behavior? (2) Are functional interactions between MeA and MePD required for the expression of opposite-sex odor preferences? (3) How do MeA and MePD regulate odor responses within the MePD and MeA, respectively? (4) Are odor and/or hormone cues conveyed directly between MeA and MePD? Together, these experiments provide a comprehensive analysis of the functional and neuroanatomical substrates by which the brain processes sexual odors and generates appropriate behavioral responses to these stimuli.

Panic disorder (PD) is a debilitating anxiety disorder that often reduces the quality of life and some of its symptoms are physical distress and fear. PD is often comorbid with other anxiety disorders and depressive disorders and also cardiovascular and respiratory illnesses. Pharmacotherapy and psychotherapy are the two most common treatment options for people with PD. A standard type of pharmacotherapy is selective serotonin reuptake inhibitors (SSRI) which in short work by increasing the level of serotonin in the brain and has been shown to be efficacious and safe. A vital brain structure that is closely linked to PD is the amygdala, and some of its functions are learning, emotional processing, and memory. There seems to be a functional and structural abnormality in the amygdala for people with PD compared to healthy individuals, for example, a smaller volume of gray matter and increased activity. The aim of the thesis is to conduct a systematic review on the effect of SSRIs on the functional alterations of the amygdala in patients suffering from PD. The present systematic review will try to answer the question: If SSRIs affect amygdala activation for PD patients compared to healthy individuals who are currently not undergoing any kind of pharmacotherapy. The results showed opposite findings; one study did not detect activation changes in the amygdala for PD patients using SSRIs, one detected higher activity in the right amygdala, whereas the other two showed a decrease in the left amygdala (one study did not specify left, bilateral, or right). More research regarding amygdala activation in PD patients using SSRIs is needed due to the small scale of studies currently available.

The mitral cells of the accessory olfactory bulb (AOB) of anuran frogs project their axons directly to the medial amygdala (MeA) along the accessory olfactory tract. An en bloc preparation of the telencephalon of the American bullfrog Lithobates catesbeiana was utilized to study a form of low-frequency inducible long-term potentiation (LTP) expressed at the synapse formed between the terminals of the accessory olfactory tract and the neurons of the MeA. Delivery of repetitive 1Hz-stimulation or sets of 5Hz tetani to the accessory olfactory tract both induced potentiation that was stable for over an hour, as measured by extracellular field recordings. LTP induced by 5Hz tetanus was associated with a decrease in paired-pulse ratio, which would be consistent with an increased probability of release contributing to the increased synaptic strength. Blockade of neither NMDA nor kainate glutamate receptors, with AP5 and UBP310 respectively, prevented LTP induction by 5Hz tetanus; however expression of LTP was partially masked in the presence of UBP310. These results suggest that kainate receptors are involved in the expression of LTP at the AOB-MeA synapse, though the means by which LTP is induced remains unclear. / Graduate / 2016-09-28