Neurobiology of learning and memory
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Neurobiol Learn Mem · Dec 2014
Learning pain-related fear: neural mechanisms mediating rapid differential conditioning, extinction and reinstatement processes in human visceral pain.
There exists converging evidence to support a role of pain-related fear in the pathophysiology and treatment of chronic pain conditions. Pain-related fear is shaped by associative learning and memory processes, which remain poorly characterized especially in the context of abdominal pain such as in irritable bowel syndrome (IBS). Therefore, using event-related functional magnetic resonance imaging (fMRI), we assessed the neural mechanisms mediating the formation, extinction and reinstatement of abdominal pain-related fear in healthy humans. Employing painful rectal distensions as clinically-relevant unconditioned stimuli (US), in this fear conditioning study we tested if differential excitatory and inhibitory learning is evocable after very few CS-US learning trials ("rapid conditioning"), and explored the underlying neural substrates of these learning and memory processes. ⋯ Abdominal pain stimuli are effective US that elicit conditioned pain-related fear even after very few learning experiences without full contingency awareness. These findings extend similar evidence of "rapid learning" in response to interoceptive US (e.g., conditioned taste aversion, conditioned nausea), and have implications for the pathophysiology and treatment of chronic abdominal pain such as in IBS.
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Reactivity to a reward is affected by prior experience with different reinforcer values of that reward, a phenomenon known as incentive relativity. Incentive relativity can be studied via the consummatory successive negative contrast (cSNC) paradigm, in which acceptance of 4% sucrose is assessed in animals that had been exposed to 32% sucrose. These downshifted animals usually exhibit significantly less sucrose acceptance than animals that always received the 4% sucrose solution. ⋯ The goal of the present experiments was to expand the knowledge on the effects of OF exposure on cSNC. We evaluated the effect OF exposure before the second downshift trial and assessed the mediational role of the adrenergic system in the effects of OF during the first and second trial of cSNC. The results indicate that OF applied before the first or second downshift trials exert opposite effects and that the adrenergic system is involved in the acquisition and consolidation of the OF information.
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Neurobiol Learn Mem · Nov 2014
RGS9-2 modulates sensory and mood related symptoms of neuropathic pain.
The signal transduction modulator Rgs9-2 (Regulator of G protein signaling 9-2) plays a key role in dopaminergic and opioidergic transmission in the striatum. Rgs9-2 is a potent modulator of opiate reward and analgesia, but its role in chronic pain remains unknown. Here, we use the spared nerve injury model (SNI), to evaluate the influence of Rgs9-2 in sensory symptoms, as well as in anxiety and depression-like behaviors observed under neuropathic pain conditions. ⋯ Furthermore, Rgs9-2 deletion exacerbates anxiety and depression like behaviors several weeks after the emergence of the neuropathic pain symptoms. Our findings also reveal a temporal and regional regulation of Rgs9-2 protein expression by neuropathic pain, as Rgs9-2 levels are reduced in the spinal cord a few days after nerve injury, whereas decreased Rgs9-2 levels in the Nucleus Accumbens (NAc) are only observed several weeks after nerve injury. Thus, adaptations in Rgs9-2 activity in the spinal cord and in the NAc may contribute to sensory and affective components of neuropathic pain.
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Neurobiol Learn Mem · Oct 2014
Frontal midline theta connectivity is related to efficiency of WM maintenance and is affected by aging.
Representations in working memory (WM) are temporary, but can be refreshed for longer periods of time through maintenance mechanisms, thereby establishing their availability for subsequent memory tests. Frontal brain regions supporting WM maintenance operations undergo anatomical and functional changes with advancing age, leading to age related decline of memory functions. The present study focused on age-related functional connectivity changes of the frontal midline (FM) cortex in the theta band (4-8 Hz), related to WM maintenance. ⋯ The connectivity strength between FM and posterior sensory cortices was shown to be sensitive to both increased memory demands and memory performance regardless of age. The coupling of frontal regions (midline and lateral) and FM-temporal cortices characterized successfully maintained trials and declined with advancing age. The findings provide evidence that a FM neural circuit of theta oscillations that serves a possible basis of active maintenance process is especially vulnerable to aging.