Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=116, 76 Female), we found that PTSD symptoms at 2-weeks were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of Fear Potentiated Startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal. Significance Statement Alterations in...

Chronic pain affects millions globally, yet no universally effective treatment exists. The primary motor cortex (M1) has been a key target for chronic pain therapies, with electrical stimulation of the M1 (eMCS) showing promise. However, the mechanisms underlying M1-mediated analgesic effects are not fully understood. We investigated the role of the primary somatosensory cortex (S1) in M1-mediated analgesia using a neuropathic pain mouse model. In this model, neuropathic pain is associated with increased spontaneous activity of layer V pyramidal neurons (LV-PNs) in the S1, partly attributed to the reduced activity of somatostatin-expressing inhibitory neurons (SST+ INs), which normally suppress LV-PNs. While manipulation of either LV-PNs or SST+ INs has been shown to alleviate pain, the role of S1 in M1-mediated analgesia has not been identified. Using multichannel silicon probes, we applied eMCS to neuropathic mice and observed significant analgesia. Histological analyses revealed that eMCS activated SST+...

Oscillatory processes are prime candidates for information coding and transfer. Hippocampal theta rhythm is a 3-12Hz sinusoidal activity that has been extensively linked to mnemonic processes. Conversely, slow oscillations (<1Hz) in the neocortex during...

INTRODUCTION: The signal detection theory (SDT) metric d-prime increases as stimuli become more discriminable. Typical perception-literature SDT paradigms use noise plus a variety of stimuli to investigate internal limitations of sensory systems; increa...

Multiple aberrant molecular processes converge to cause neuronal death in amyotrophic lateral sclerosis (ALS). That each of these defects is a potential target for therapeutic intervention makes ALS a prime candidate for combinatorial therapies. Glutama...

PTI-00703TM (703) is a derivative from the Amazon rain forest woody vine, Uncaria tomentosa (Cat's claw) previously discovered by our group to inhibit the formation, deposition and growth of Alzheimer's beta-amyloid protein (Aβ) deposits. In the present study assay guided fractionation and HPLC were used to isolate, characterize and test water-soluble active ingredients within 703 that possess potent Aβ fibrillogenesis inhibitory activity. Up to 7 major water-soluble ingredients (collectively known as PTI-777) were purified and tested in various assays to determine their efficacy in comparison to 703 and to major alkaloids present in Cat's claw. Thioflavin T fluorometry, Congo red staining and electron microscopy data demonstrate that PTI-777 is a more potent inhibitor of Aβ fibrillogenesis than 703 alone. In one study, incubation of 703 with Aβ 1-42 for 1 day (1:1 weight ratio) caused a 53.2% disruption of Aβ fibrils, whereas PTI-777 resulted in a significant 87.3% inhibiton. In a rodent model 1 week co-i...

Mouse lines with tetracycline-controlled gene expression in specific neuronal populations provide valuable tools for studying their development, function, connectivity, and pathology in vivo. Our initial goal was to generate a mouse model that could express amyotrophic lateral sclerosis-associated genes specifically in spinal cord motor neurons under the control of the HB9 promoter. However, HB9-tTA mice unexpectedly direct target gene expression in a small subset of dorsal horn neurons. These mice represent a new tool for scientists who are interested in studying these spinal cord neurons.

The importance of animal models to an understanding of the development and plasticity of visual functions was evident from the outset of the long experimental collaboration of David Hubel and Torsten Wiesel in the early 1960s. Their initial work on kittens had massive impact in part because of the recognition that kittens share with primates substantial similarities of visual system organization and plasticity (e.g., eye-specific lamination of the thalamus and columnar organization of the visual cortex), as well as comparable visual abilities (including stereoscopic vision). In addition the plasticity demonstrated in response to early periods of selected visual exposure provided a glimpse into the origins of amblyopia. Five decades ago my laboratory developed a method for the fast measurement of visual thresholds in kittens in order to capture the consequences for spatial vision of the rapid physiological changes that occurred in the visual cortex during both typical development and those that follow vario...

A classical way of studying human episodic memory is free recall of randomly assembled words, where participants are presented with a list of words and are requested to report as many words as they could. Many experimental studies highlighted the main c...

Fredrick John Seil, MD was born on November 9, 1933 of German parentage in the town of Neu schowe (Nove Sove) in the former Yugoslavia (now Ravno Selo, Serbia). He emigrated with his family to the United States in March of 1938.