Fear learning and aversive stimuli differentially change excitatory synaptic transmission in perisomatic inhibitory cells of the basal amygdala

Inhibitory circuits in the basal amygdala (BA) have been shown to play a crucial role in associative fear learning. How the excitatory synaptic inputs received by BA GABAergic interneurons are influenced by memory formation, a network parameter that may contribute to learning processes, is still largely unknown. Here, we investigated the features of excitatory synaptic transmission received by the three types of perisomatic inhibitory interneurons upon cue-dependent fear conditioning and aversive stimulus and tone presentations without association. Acute slices were prepared from transgenic mice: one group received tone presentation only (conditioned stimulus, CS group), the second group was challenged by mild electrical shocks unpaired with the CS (unsigned unconditioned stimulus, unsigned US group) and the third group was presented with the CS paired with the US (signed US group). We found that excitatory synaptic inputs (miniature excitatory postsynaptic currents, mEPSCs) recorded in distinct interneuron types in the BA showed plastic changes with different patterns. Parvalbumin (PV) basket cells in the unsigned US and signed US group received mEPSCs with reduced amplitude and rate in comparison to the only CS group. Coupling the US and CS in the signed US group caused a slight increase in the amplitude of the events in comparison to the unsigned US group, where the association of CS and US does not take place. Excitatory synaptic inputs onto cholecystokinin (CCK) basket cells showed a markedly different change from PV basket cells in these behavioral paradigms: only the decay time was significantly faster in the unsigned US group compared to the only CS group, whereas the amplitude of mEPSCs increased in the signed US group compared to the only CS group. Excitatory synaptic inputs received by PV axo-axonic cells showed the least difference in the three behavioral paradigm: the only significant change was that the rate of mEPSCs increased in the signed US group when compared to the only CS group. These results collectively show that associative learning and aversive stimuli unpaired with CS cause different changes in excitatory synaptic transmission in BA perisomatic interneuron types, supporting the hypothesis that they play distinct roles in the BA network operations upon pain information processing and fear memory formation

Novel bio-spectroscopic imaging reveals disturbed protein homeostasis and thiol redox with protein aggregation prior to hippocampal CA1 pyramidal neuron death induced by global brain ischemia in the rat

Global brain ischemia resulting from cardiac arrest and cardiac surgery can lead to permanent brain damage and mental impairment. A clinical hallmark of global brain ischemia is delayed neurodegeneration, particularly within the CA1 subsector of the hippocampus. Unfortunately, the biochemical mechanisms have not been fully elucidated, hindering optimization of current therapies (i.e., therapeutic hypothermia) or development of new therapies. A major limitation to elucidating the mechanisms that contribute to neurodegeneration and understanding how these are influenced by potential therapies is the inability to relate biochemical markers to alterations in the morphology of individual neurons. Although immunocytochemistry allows imaging of numerous biochemical markers at the sub-cellular level, it is not a direct chemical imaging technique and requires successful "tagging" of the desired analyte. Consequently, important biochemical parameters, particularly those that manifest from oxidative damage to biological molecules, such as aggregated protein levels, have been notoriously difficult to image at the cellular or sub-cellular level. It has been hypothesized that reactive oxygen species (ROS) generated during ischemia and reperfusion facilitate protein aggregation, impairing neuronal protein homeostasis (i.e., decreasing protein synthesis) that in turn promotes neurodegeneration. Despite indirect evidence for this theory, direct measurements of morphology and ROS induced biochemical damage, such as increased protein aggregates and decreased protein synthesis, within the same neuron is lacking, due to the unavailability of a suitable imaging method. Our experimental approach has incorporated routine histology with novel wide-field synchrotron radiation Fourier transform infrared imaging (FTIRI) of the same neurons, ex vivo within brain tissue sections. The results demonstrate for the first time that increased protein aggregation and decreased levels of total protein occur in the same CA1 pyramidal neurons 1 day after global ischemia. Further, analysis of serial tissue sections using X-ray absorption spectroscopy at the sulfur K-edge has revealed that CA1 pyramidal neurons have increased disulfide levels, a direct indicator of oxidative stress, at this time point. These changes at 1 day after ischemia precede a massive increase in aggregated protein and disulfide levels concomitant with loss of neuron integrity 2 days after ischemia. Therefore, this study has provided direct support for a correlative mechanistic link in both spatial and temporal domains between oxidative stress, protein aggregation and altered protein homeostasis prior to irreparable neuron damage following global ischemia. © 2015 Elsevier Inc. All rights reserved

Mesozoic and Cenozoic Plate Evolution of the Caribbean Region

The reconstruction of Caribbean plate history is an uncertain task, but a task that has intrigued generations of geologists. Each worker has turned to the task of historical interpretation influenced by a particular set of experiences or a special approach, and the results have been accordingly varied. A complete history of interpretations would form the subject of a fascinating chapter in the history of geological philosophy, but such is not the purpose of this chapter. Instead, I will dwell on a set of data that call for what I believe to be a relatively conservative view of Cretaceous and Tertiary plate history. My own interpretation is based heavily on my own or my students’ field experiences in the northeastern West Indies, Guatemala, Belize, and Venezuela, as well as extensive field excursions in Hispaniola, Jamaica, the Lesser Antilles, Central America, and the Dutch Antilles. I am further heavily influenced by the results of the Deep Sea Drilling Project (DSDP), Leg 15, which produced information of fundamental interest in the Venezuelan and Colombian Basins, and by several dissertations of the Princeton University group in northern Venezuela