Neuronal Adaptations during Amygdala-Dependent Learning and Memory

The amygdala, a structure deep in the temporal lobe of the brain, is an essential region for emotional and fearful processing. Neuronal coding in the lateral nucleus of the amygdala (LA) endows the brain with the ability to acquire enduring aversive associations, physically represented by experience-dependent synaptic modifications within a small population of neurons selectively recruited during learning. Understanding the precise mechanisms underlying neuronal selection and plasticity during memory formation has been among the most fundamental questions in neuroscience for the past century. Defining the distribution of neuronal activity would further elucidate the conditions by which memories are expressed and how neurons are differentially recruited into distinct memory engrams. The aim of this thesis was to utilize reliable methods to capture, visualize, monitor and modulate defined neuronal populations to expand our knowledge regarding the above questions. Chapter 1 of this thesis is an overview of the history of progress in understanding fear and eye-blink conditioning. It describes the core principles and particularly highlights recent findings that have been elucidated in the process by which fear memory and motor learning are acquired and encoded. Chapter 2 describes a novel method to study fear memory traces. Arc::dVenus transgenic mice were used to visualize neurons that underwent cellular modifications during fear learning in the lateral amygdala (LA). Our findings demonstrate that intrinsic neuronal excitability is a major driving force for the fear memory neuronal selection. This chapter also demonstrates that the potentiation of glutamatergic synaptic transmission from the thalamic input pathway to the LA is learning-specific, and highly localized to Arc expressing neurons. Chapter 3 reports the distinct pattern of Arc expression following learning in the art of the LA. We find that this subregion demonstrates a chronically enduring plasticity by which neurons in this subregion are uniquely active only upon the acquisition of novel aversive associations. Chapter 4 focuses on the role of somatostatin+ (SOM+) interneurons in the lateral division of central nucleus of the amygdala (CeL) in eye-blink conditioning. We find that the CeL has a regulatory effect on associative eyelid responses, indicating that eye-blink conditioning shares key mechanistic components of fear associative learning responses. Chapter 5 is a general discussion about the outcomes and major conclusions of our studies. In addition, it proposes future approaches that could advance some important unanswered questions in the field

Human Gaze Following Response Is Affected by Visual Acuity

The present study investigated how gaze following eye movements are affected by stimulus contrast and spatial frequency and by aberrations in central visual acuity due to refractive errors. We measured 30 healthy subjects with a range of visual acuities but without any refractive correction. Visual acuity was tested using a Landolt-C chart. Subjects were divided into three groups with low, intermediate, or good visual acuity. Gaze following responses (GFR) to moving Gabor patches were recorded by video-oculography. In each trial, the subjects were presented with a single Gabor patch with a specific spatial frequency and luminance contrast that moved sinusoidally in the horizontal plane. We observed that GFR gain decreased with increasing spatial frequency and decreasing contrast and was correlated with visual acuity. GFR gain was lower and decreased more for subjects with lower visual acuity; this was especially so for lower stimulus contrasts that are not tested in standard acuity tests. The largest differences between the groups were observed at spatial frequencies around 4 cpd and at contrasts up to 10%. Aberrations in central visual acuity due to refractive errors affect the GFR response depending on the contrast and spatial frequency of the moving stimulus. Measuring this effect may contribute to a better estimate of changes in visual function as a result of aging, disease, or treatments meant to improve vision

Adipose Derived Stem Cells Exert Immunomodulatory Effects on Natural Killer Cells in Breast Cancer

Objective Adipose derived stem cells (ASCs), as one of the important stromal cells in the tumor microenvironment, are determined with immunomodulatory effects. The principle aim of this study was to evaluate the immunosuppressive effects of ASCs on natural killer (NK) cells. Materials and Methods In this experimental study, we assessed the expressions of indolamine 2, 3-dioxygenase (IDO1), IDO2 and human leukocyte antigen-G5 (HLA-G5) in ASCs isolated from breast cancer patients with different stages as well as normal individuals, using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Immunomodulatory effects of ASCs on the expression of CD16, CD56, CD69, NKG2D, NKp30, NKG2A and NKp44 was also assessed in peripheral blood lymphocytes (PBLs) by flow-cytometry. Results Our result showed that IDO1, IDO2 and HLA-G5 had higher mRNA expressions in ASCs isolated from breast cancer patients than those from normal individuals (P>0.05). mRNA expression of these molecules were higher in ASCs isolated from breast cancer patients with stage III tumors than those with stage II. The indirect culture of ASCs isolated from breast cancer patients and normal individuals with activated PBLs significantly reduced NKG2D+ and CD69+ NK cells (P<0.05). Conclusion Results of the present study suggest more evidences for the immunosuppression of ASCs on NK cells, providing conditions in favor of tumor immune evasion

The success rate of small renal mass core needle biopsy and its impact on lowering benign resection rate

BackgroundSmall renal mass (SRM) biopsy remains under-utilized due to stigma. Meanwhile, the alarmingly high benign findings in resected kidney masses highlight the need for improved preoperative diagnosis and patient selection.MethodsThe purpose of this study is to review the success rate of SRM biopsy and to evaluate its impact on patient management. A total of 168 percutaneous image-guided core needle biopsies (CNBs) of SRMs were retrieved at a tertiary academic center between 2015 and 2019. Subsequent treatment choices, side effects and outcomes were retrospectively reviewed.ResultsThe diagnostic rate of CNB was 86.9%. Benign neoplasms accounted for a significant portion (14.3%) of SRM. Renal cell carcinomas (RCCs) were the most common diagnoses (69.6%) as expected. In biopsy-resection correlation, the positive predictive value of CNB was 100%. Tumor typing and subtyping by CNB were highly accurate, 100% and 98.3% respectively. Nuclear grading for clear cell RCC was accurate in 83.8% cases. The CNB results had significant impact on treatment. Most patients with RCCs underwent either resection (54.1%) or ablation (33.9%), in contrast to observation in benign neoplasms (90.5%). Most importantly, the benign resection rate (3.2%) in this series was much lower than the national average.ConclusionCNB provided accurate diagnoses for the majority of SRMs and revealed benign diagnoses in a subset of clinically suspicious lesions. Employment of CNB in suspicious SRM may help avoid overtreatment for benign lesions