Studies have suggested the possibility that there is sensory (SS) afferent signaling from white adipose tissue (WAT) to the brain, which may play an important role in communication with the brain sympathetic nervous system (SNS) outflow to WAT. Therefore, we tested whether the SNS-SS feedback loop between the subcutaneous inguinal WAT (IWAT) and the epididymal WAT (EWAT) exists. These fat pads were chosen due to 1) their divergent role in manifestation of metabolic disorders with the IWAT being beneficial and the EWAT being detrimental, as well as 2) different lipolytic response to glucoprivic 2-deoxyglucose (2DG). By using retrograde tract tracers Fast Blue (FB) and Fluorogold (FG), we found that the IWAT is more innervated than EWAT by both the SS and SNS ganglia (T13-L3). Surprisingly, we found ~12-17% of double-labeled cells in the SNS and SS ganglia innervating fat depots, implying SNS-SS crosstalk loops between the IWAT and EWAT. Increased neuronal activation by 2DG was observed in the SNS ganglia to both IWAT and EWAT but not in the SS dorsal root ganglia. In addition, 2DG induced lipolysis in both fat pads with greater lipolytic properties in the IWAT as a result of higher density of the SNS-SS fibers. Collectively, our results show neuroanatomical reality of the IWAT and EWAT SNS-SS neural crosstalk with a coordinated control of lipolytic function.

As both the major input and output of the hippocampal formation, the entorhinal cortex (EC) occupies a pivotal position in the medial temporal lobe. The discovery of grid cells in the medial entorhinal cortex (mEC) has led to this region being widely implicated in spatial information processing. Importantly, the EC is also the first area affected by dementia pathology, with neurons appearing particularly susceptible to degeneration. Despite this, little is known about how pathology affects the functional output of mEC neurons, either in their ability to coordinate firing to produce network oscillations, or to represent information regarding the external environment. This thesis will use electrophysiological techniques to examine how dementia pathology contributes to the breakdown of mEC neuronal networks using the rTg4510 mouse model of tauopathy. The first 2 results chapters will show how the anatomical organisation along the dorso-ventral axis of the mEC has profound influence on the network activity that can be observed both in brain slices and awake-behaving mice. It will further show how deficits in network activity in rTg4510 mice occur differentially across this axis, with dorsal mEC appearing more vulnerable to changes in oscillatory function than ventral. The third results chapter will begin to explore the relationship between global network activity and the external environment, showing that rTg4510 mice display clear deficits in the relationship between oscillation properties and locomotor activity. Finally, the underlying basis for these changes will be examined, through the recording of single-unit activity in these mice. It will show a decreased tendency for mEC neurons to display firing rates modulated by running speed, as well as an almost complete breakdown of grid cell periodicity after periods of tau overexpression. Understanding how dementia pathology produces changes to neuronal function and ultimately cognition is key for understanding and treating the disease. This thesis will therefore provide novel insights into the dysfunction of the EC during dementia pathology.

The dorsal anterior cingulate cortex (dACC) has been implicated in a broad range of cognitive and emotional functions, including the processing of negative emotion. Furthermore, abnormalities in dACC activity have been associated with anxiety and depression, disorders in which negative emotion is dysregulated. Thus, a better understanding of the precise contributions of the dACC to negative emotion could give us important insights into the neurobiological mechanisms underlying these debilitating neuropsychiatric disorders. However, despite extensive study of the dACC, its precise role in negative emotion is unclear. Instead there is mounting evidence that rather than being one functionally homogeneous region, subregions of the dACC may have distinct functional roles. This evidence is largely correlational, and interventional studies in experimental animals are required to address this. Accordingly, the work in this thesis causally assessed the contributions of two spatially distinct subregions of the dACC (rostral and caudal) to the regulation of the behavioural and cardiovascular correlates of negative emotion in the common marmoset (Callithrix jacchus). These dACC subregions were targeted with indwelling cannulae to enable pharmacological manipulations to be carried out in a range of tasks, used to assess distinct components of negative emotion, such as conditioned fear and anxiety. The findings suggest that the rostral dACC and the caudal dACC do indeed have distinct contributions to the expression of negative emotion and the regulation of anxiety, respectively. Furthermore, an assessment of the anterograde projections of these subregions provides anatomical support for the observed functional differences.

Orientadora: Tatiana Lima Ferreira / Dissertação (mestrado) - Universidade Federal do ABC. Programa de Pós-Graduação em Neurociência e Cognição, 2013.

Orientadora: Profa. Dra. Tatiana Lima Ferreira / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Neurociência e Cognição, 2014.

Macrophages and other cells of the innate immune system recognize foreign particles that could be potentially dangerous and respond by initiating an inflammatory response. The biologically active chemical mediators of this response called pro-inflammatory cytokines are produced in various myeloid derived immune cells and can affect other cells of the body. Interleukin-1β, a pro-inflammatory cytokine, has been shown to have direct effects on dorsal root ganglion (DRG) cell bodies including the upregulation and direct release of a nociceptive neurotransmitter called substance P (SP). Using a zymosan-induced model of systemic inflammation, we hypothesized that murine DRG neurons and the nerve processes associated with them in the dorsal horn of the spinal cord (SC) at the L1 level will show an upregulation of SP expression in response to inflammation in the peritoneum. Experimental mice were treated with a zymosan suspension (500mg/kg, intraperitoneal injection), and control mice received sterile filtered solution (intraperitoneal injection). Both DRG and SC specimens were collected after in situ fixation and subjected to immunofluorescence staining to label SP. Using confocal microscopy, fluorescence microscopy, and image analysis software this expression of SP was quantified and compared. In both tissue specimen groups, an increase in SP expression was discovered in zymosan treated mice. The exact cause of this increase was not specifically determined in this experiment. This experiment provided valuable insight about how a systemic inflammatory response can affect sensory nerve function. Successful methods for further experimentation were identified and information about the zymosan model of inflammation was obtained

Neuroplasticity has been researched in many different ways, from the growing neonatal brain to neural responses to trauma and injury. According to recent research, neuroplasticity is also prevalent in the ability of the brain to repurpose areas that are not of use, like in the case of a loss of a sense. Specifically, behavioral studies have shown that deaf humans (Bavalier and Neville, 2002) and cats have increased visual ability, and that different areas of the auditory cortex enhance specific kinds of sight. One such behavioral test demonstrated that the dorsal zone (DZ) of the auditory cortex enhances sensitivity to visual motion through cross-modal plasticity (Lomber et. al., 2010). Current research seeks to examine the anatomical structures responsible for these changes through analysis of excitatory neuron dendritic spine density and spine head diameter. This present study focuses on the examination of DZ neuron spine density, distribution, and size in deaf and hearing cats to corroborate the visual changes seen in behavioral studies. Using Golgi-stained tissue and light microscopy, our results showed a decrease in overall spine density but slight increase in spine head diameter in deaf cats compared to hearing cats. These results, along with several other studies, support multiple theories on how cross-modal reorganization of the auditory cortex occurs after deafening

acase@tulane.edu

Several factors contribute to the failure of the central nervous system (CNS) to regenerate after injury. These include inhibition of axonal growth by myelin and glial scar associated molecules, as well as the intrinsic inability of adult CNS neurons to grow long axons in environments that are permissive for younger neurons. Neurons in the peripheral nervous system (PNS) display a much higher capacity to regenerate after injury than CNS neurons, as shown by conditioning lesion experiments and by microtransplantation of dorsal root ganglia neurons into CNS white matter tracts. Our central hypothesis is that neurons of the PNS express specific regeneration associated genes that mediate their enhanced growth response after injury. We have employed a combination of subtractive hybridization, microarray comparison and promoter analysis to probe for genes specific to neurons of the dorsal root ganglia (DRG), using cerebellar granule neurons (CGN) as a reference. We have identified over a thousand different genes, many of whose products form interaction networks and signaling pathways. Moreover, we have identified several dozen transcription factors that may play a role in establishing DRG neuron identity and shape their responses after injury. One of these transcription factors is Signal Transducer and Activator of Transcription 3 (STAT3), previously known to be upregulated in the PNS after a conditioning lesion but not known to be specific to the PNS. Using a real time PCR and immunochemical approaches we have shown that STAT3 is constitutively expressed and selectively active in DRG neurons both in culture and in vivo. We show that the overexpression of wild type STAT3 in cerebellar granule neurons leads to the formation of supernumerary neurites, whereas the overexpression of constitutively active STAT3-C leads to a 20% increase in total neurite outgrowth. It is hoped that the genetic delivery of STAT3-C, potentially combined with co-activators of transcription, will improve functional regeneration of CNS axons in vivo.

The structure of afferent neurons is pseudounipolar. Studies suggest that they relay action potentials (APs) to both directions of the T-junctions to reach the cell body and the spinal cord. Moreover, the somata are electrically excitable and shown to be able to transmit the signals to associated satellite cells. Our study demonstrates that this transmission can go further and pass onto passive neighbouring somata, if they are in direct contact with same satellite cells. The neurons activate the satellite cells by releasing ATP. This triggers the satellite cells to exocytose acetylcholine to the neighbouring neurons. In addition, the ATP inhibits the nicotinic receptors of the neurons by activating P2Y receptors and initiating the G-protein-mediated pathway, thus reducing the signals that return to the neurons that initiated the signals. This “sandwich synapse” represents a unique pathway by the ectopic release between the somata and the satellite cells.