ABSTRACT
The lateral amygdala (LA) plays a critical role in the formation of fear-conditioned associative memories. Previous studies have used c-fos regulated expression to identify a spatially restricted population of neurons within the LA that is specifically activated by fear learning. These neurons are likely to be a part of a memory engram, but, to date, functional evidence for this has been lacking. We show that neurons within a spatially restricted region of the LA had an increase in both the frequency and amplitude of spontaneous postsynaptic currents (sPSC) when compared to neurons recorded from home cage control mice. We then more specifically addressed if this increased synaptic activity was limited to learning-activated neurons. Using a fos-tau-LacZ (FTL) transgenic mouse line, we developed a fluorescence-based method of identifying and recording from neurons activated by fear learning (FTL+ ) in acute brain slices. An increase in frequency and amplitude of sPSCs was observed in FTL+ neurons when compared to nonactivated FTL- neurons in fear-conditioned mice. No learning-induced changes were observed in the action potential (AP) input-output relationships. These findings support the idea that a discrete LA neuron population forms part of a memory engram through changes in synaptic connectivity.
Subject(s)
Basolateral Nuclear Complex/physiology , Conditioning, Classical/physiology , Fear , Memory/physiology , Neurons/physiology , Synapses/physiology , Action Potentials , Animals , Electroshock , Male , Mice, Inbred C57BL , Mice, Transgenic , Miniature Postsynaptic PotentialsABSTRACT
The kynurenine pathway has been implicated as a major component of the neuroinflammatory response to brain injury and neurodegeneration. We found that the neurotoxic kynurenine pathway intermediate quinolinic acid (QUIN) is rapidly expressed, within 24 h, by reactive microglia following traumatic injury to the rodent neocortex. Furthermore, administration of the astrocytic protein metallothionein attenuated this neuroinflammatory response by reducing microglial activation (by approximately 30%) and QUIN expression. The suppressive effect of MT was confirmed upon cultured cortical microglia, with 1 mug/ml MT almost completely blocking interferon-gamma induced activation of microglia and QUIN expression. These results demonstrate the neuroimmunomodulatory properties of MT, which may have therapeutic applications for the treatment of traumatic brain injury.
Subject(s)
Brain Injuries/pathology , Gene Expression Regulation/drug effects , Metallothionein/pharmacology , Microglia/drug effects , Quinolinic Acid/metabolism , Analysis of Variance , Animals , Brain Injuries/drug therapy , Brain Injuries/metabolism , Cell Count/methods , Cells, Cultured , Cerebral Cortex/cytology , Culture Media, Conditioned/pharmacology , Dose-Response Relationship, Drug , Ferritins/metabolism , Gas Chromatography-Mass Spectrometry , Glial Fibrillary Acidic Protein/metabolism , Interferon-gamma/pharmacology , Microglia/chemistry , Neocortex/metabolism , Neocortex/pathology , Neurons/pathology , Quinolinic Acid/analysis , Rats , Rats, WistarABSTRACT
STUDY OBJECTIVES: Incomplete follow-up can bias interpretation of data that are collected in longitudinal studies. We noted that many patients failed to return for follow-up in a study of effect of lung volume reduction surgery (LVRS) on quality of life (QOL). Accordingly, we designed this investigation to determine the reasons patients dropped out, and to assess differences between those who continued in the study (attendees) and those who did not (nonattendees). DESIGN: Telephone survey. SUBJECTS: Patients with advanced emphysema who had undergone LVRS and had previously agreed to participate in a longitudinal QOL study. RESULTS: No differences were found with regard to age, gender, preoperative pulmonary function, or oxygen use between attendees and nonattendees. Long-term mortality in nonattendees (27%) was considerably greater than that seen in attendees (3%, p < 0.05). Distance from the hospital, financial burden, and living out of the region were the most common reasons cited by surviving nonattendees for their failure to return for follow-up. CONCLUSIONS: Studies reporting the long-term mortality after LVRS can be biased in the direction of underestimating the true value if they are compromised by incomplete follow-up.
Subject(s)
Pneumonectomy , Pulmonary Emphysema/mortality , Adult , Aged , Bias , Comorbidity , Data Collection , Epidemiologic Measurements , Female , Forced Expiratory Volume , Humans , Longitudinal Studies , Male , Middle Aged , Patient Dropouts , Pulmonary Emphysema/physiopathology , Pulmonary Emphysema/surgery , Quality of Life , Survival Rate , Total Lung Capacity , Vital CapacityABSTRACT
The value of a one-stage silver staining technique for nucleolar organizer region (NOR)-associated protein was investigated as a predictor of clinical outcome in 100 rectal adenocarcinomas. In formalin-fixed tissues, a variety of silver-stained structures ranging from 0.5 to 7 microns are seen, the abundance of which bears no relation to prognosis, cell proliferation, or ploidy. Evidence is presented that the silver-stained structures are the result of coalescence of smaller particles caused by formalin fixation, and that assessment of NOR activity is not reliable in routinely formalin-fixed archival tissues.