Intracerebral injection of brain extracts containing amyloid or tau aggregates in transgenic animals can induce cerebral amyloidosis and pathology. We extracted pure populations oligomers directly from the cortex Alzheimer disease (AD) brain. These are potent inhibitors long term potentiation (LTP) hippocampal slices disrupt memory wild type mice. observed for first time that these authentic brain-derived propagate abnormal conformation endogenous murine after prolonged incubation. The...

Cognitive deficits such as impaired decision-making can be a consequence of persistent pain. Normal functions the intact amygdala and prefrontal cortex are required for emotion-based that relies on ability to assess risk, attribute value, identify advantageous strategies. We tested hypothesis pain-related cognitive result from amygdala-driven impairment medial cortical (mPFC) function. To do this, we used electrophysiological single-unit recordings in vivo , patch clamp brain slices, various...

Pain has a strong emotional–affective dimension, and the amygdala plays key role in emotionality. Mechanisms of pain-related changes were studied at cellular molecular levels model arthritis pain. The influence arthritic condition induced <i>in vivo</i> on synaptic transmission group I metabotropic glutamate receptor (mGluR1 mGluR5) function was examined vitro</i> using whole-cell voltage-clamp recordings neurons central nucleus (CeA). G-protein-coupled mGluRs are implicated various forms...

1. In the spinalized cat, nociceptive spinal neurons with knee input show enhanced responses to mechanical stimulation of that joint once an inflammation has developed in knee. Enhanced may result from increased afferent inflow as well modifications processing within cord. To examine significance these components, we tested 30 chloralose-anesthetized, cats whether, during development arthritis, changes responsiveness are restricted inflamed or whether is altered general. While continuously...

1. In 22 anesthetized rats we studied the involvement of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in generation maintenance hyperexcitability spinal cord neurons with knee input that develops course an acute inflammation knee. all experiments one neuron was identified, responses to mechanical stimuli receptive fields were monitored before after induction by intra-articular injections kaolin carrageenan into joint cavity. most multibarrel electrodes used administer specific NMDA...

Recent biochemical and behavioral data suggest right-hemispheric lateralization of amygdala functions in pain. Our previous electrophysiological studies showed pain-related neuroplasticity the latero-capsular division central nucleus (CeLC) right brain hemisphere. Here we determined differences processing signals versus left CeLC neurons. Individual neurons were recorded extracellularly before after induction an arthritis pain state anesthetized rats. Brief innocuous noxious test stimuli...

A major site of extrahypothalamic expression corticotropin-releasing factor (CRF) and its G-protein-coupled CRF1 CRF2 receptors is the amygdala, a key player in emotions affective disorders. Pain-related plasticity laterocapsular division central nucleus amygdala (CeLC) generates emotional-affective responses anxiety-like behavior. receptor antagonists have anxiolytic effects. Although both couple positively to adenylyl cyclase, they can opposite effects, but underlying mechanism unknown....

Pain-related hyperactivity in the amygdala leads to deactivation of medial prefrontal cortex (mPFC) and decision-making deficits. The mechanisms pain-related inhibition mPFC are not yet known. Here, we used extracellular single-unit recordings prelimbic neurons determine role GABA(A) receptors metabotropic glutamate receptor (mGluR) subtypes, mGluR1 mGluR5, activity changes neurons. Background evoked decreased after arthritis induction. To changes, same neuron was recorded continuously...

The medial prefrontal cortex (mPFC) serves major executive functions. mPFC output to subcortical brain areas such as the amygdala controls emotional processing and plays an important role in fear extinction. Impaired function correlates with extinction deficits anxiety disorders PTSD cognitive decision-making neuropsychiatric persistent pain. Controlling is a desirable therapeutic goal but functional differences of cell types (pyramidal cells interneurons) regions (infralimbic prelimbic)...

The medial prefrontal cortex (mPFC) serves executive functions that are impaired in neuropsychiatric disorders and pain. Underlying mechanisms remain to be determined. Here we advance the novel concept metabotropic glutamate receptor 5 (mGluR5) fails engage endocannabinoid (2-AG) signaling overcome abnormal synaptic inhibition pain, but restoring allows mGluR5 increase mPFC output hence inhibit pain behaviors mitigate cognitive deficits. Whole-cell patch-clamp recordings were made from layer...

Abstract Chronic pain is associated with neuroplastic changes in the amygdala that may promote hyper-responsiveness to mechanical and thermal stimuli (allodynia hyperalgesia) and/or enhance emotional affective consequences of pain. Stress promotes dynorphin-mediated signaling at kappa opioid receptor (KOR) hypersensitivity rodent models functional Here, we tested hypothesis KOR circuits central nucleus (CeA) undergo neuroplasticity chronic neuropathic resulting increased sensory responses....

Abstract The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway activated by stress, we determined its role DNIC using a model stress-induced pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting opioid-induced hyperalgesia. Fourteen after priming, when hyperalgesia was resolved, exposed to environmental stress and evaluated...

1. In 15 alpha-chloralose-anesthetized cats we studied the presence of tonic descending inhibition (TDI) spinal neurons with input from knee and its modulation during an acute inflammation this joint. TDI articular was assessed by applying reversible cold blocks to lower thoracic cord. The amount estimated induction and/or increase resting discharges responses mechanical stimuli other structures transitory blocks. each experiment one or a few were investigated while joint in normal condition...