The Journal of neuroscience : the official journal of the Society for Neuroscience
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Chronic pain associated with injury or disease can result from dysfunction of sensory afferents whereby the threshold for activation of pain-sensing neurons (nociceptors) is lowered. Neurotrophic factors control nociceptor development and survival, but also induce sensitization through activation of their cognate receptors, attributable, in part, to the modulation of ion channel function. Thermal pain is mediated by channels of the transient receptor potential (TRP) family, including the cold and menthol receptor TRPM8. ⋯ Nerve growth factor induced mild cold sensitization, consistent with TrkA expression in TRPM8 neurons. However, bradykinin failed to alter cold sensitivity even though its receptor expresses in a subset of TRPM8 neurons. These results show for the first time that only select neurotrophic factors induce cold sensitization through TRPM8 in vivo, unlike the broad range of proalgesic agents capable of promoting heat hyperalgesia.
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Neural circuits maintain a precise organization that is vital for normal brain functions and behaviors, but become disrupted during neurological disease. Understanding the connection between wiring accuracy and function to measure disease progression or recovery has been difficult because of the complexity of behavioral circuits. The olfactory system maintains well-defined neural connections that regenerate throughout life. ⋯ Interestingly, the degree of functional recovery tracked directly with circuit restoration. Together, these data demonstrate that hAPP-induced circuit disruption and subsequent recovery can occur rapidly and that behavior can provide a measure of circuit organization. Thus, olfaction may serve as a useful biomarker to both follow disease progression and gauge potential recovery.
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The rising proportion of elderly people worldwide will yield an increased incidence of age-associated cognitive impairments, imposing major burdens on societies. Consequently, growing interest emerged to evaluate new strategies to delay or counteract cognitive decline in aging. Here, we assessed immediate effects of anodal transcranial direct current stimulation (atDCS) on cognition and previously described detrimental changes in brain activity attributable to aging. ⋯ RS-fMRI revealed enhanced anterior and reduced posterior functional brain connectivity. atDCS significantly improved performance in older adults up to the level of younger controls; significantly reduced task-related hyperactivity in bilateral prefrontal cortices, the anterior cingulate gyrus, and the precuneus; and induced a more "youth-like" connectivity pattern during RS-fMRI. Our results provide converging evidence from behavioral analysis and two independent functional imaging paradigms that a single session of atDCS can temporarily reverse nonbeneficial effects of aging on cognition and brain activity and connectivity. These findings may translate into novel treatments to ameliorate cognitive decline in normal aging in the future.
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Gamma frequency (30-80 Hz) oscillations are implicated in memory processing. Such rhythmic activity can be generated intrinsically in the CA3 region of the hippocampus from where it can propagate to the CA1 area. To uncover the synaptic mechanisms underlying the intrahippocampal spread of gamma oscillations, we recorded local field potentials, as well as action potentials and synaptic currents in anatomically identified CA1 and CA3 neurons during carbachol-induced gamma oscillations in mouse hippocampal slices. ⋯ The firing of phase-coupled CA1 pyramidal cells was controlled principally by their inhibitory inputs, which dominated over excitation. Our results indicate that the synchronous firing of CA3 pyramidal cells rhythmically recruits CA1 interneurons and that this feedforward inhibition generates the oscillatory activity in CA1. These findings identify distinct synaptic mechanisms underlying the generation of gamma frequency oscillations in neighboring hippocampal subregions.
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Neural signatures of somatosensory awareness have often been studied by examining EEG responses to hardly detectable stimuli. Previous reports consistently showed that event-related potentials (ERPs) measured over early somatosensory cortex diverge for detected and missed perithreshold stimuli at 80-100 ms after stimulus onset. So far, however, all previous studies have operationalized somatosensory awareness as binary stimulus detection. ⋯ Furthermore, later in the analysis window, the subjective rating of stimuli correlated with the amplitude of the N140 component and with a broadly distributed P300 component. By DCM modeling, these late effects were explained in terms of recurrent processing within the network of somatosensory and premotor cortices. Our results indicate that early neural activity in the somatosensory cortex can reflect the subjective quality of tactile perception.