Voltage-gated CaV2.2 calcium channels are expressed in nociceptors at presynaptic terminals, soma, and axons. CaV2.2 channel inhibitors applied to the spinal cord relieve pain in humans and rodents, especially during pathological pain, but a biological function of nociceptor CaV2.2 channels in processing of nociception, outside presynaptic terminals in the spinal cord, is underappreciated. Here, we demonstrate that functional CaV2.2 channels in peripheral axons innervating skin are required for capsaicin-induced heat hypersensitivity in male and female mice. We show that CaV2.2 channels in TRPV1-nociceptor endings are activated by capsaicin-induced depolarization and contribute to increased intracellular calcium. Capsaicin induces hypersensitivity of both thermal nociceptors and mechanoreceptors, but only heat hypersensitivity depends on peripheral CaV2.2 channel activity, and especially a cell type-specific CaV2.2 splice isoform. CaV2.2 channels at peripheral nerve endings might be important therapeutic t...

Neuroimaging data reveal that a functional locus ceruleus-noradrenaline (LC-NA) system is critical in maintaining cognitive performance during aging. However, older adults show reduced LC integrity and altered functional connectivity, demonstrating both structural declines and dysfunction. The LC-NA system mediates mechanisms of attention processing and eye tracking studies have shown that older adults are slower and more distractible compared with young adults in visual search tasks. Prior studies have shown that mindfulness meditation modulates LC noradrenergic activity, increases gray matter volume in the brainstem, and improves attentional control. Thus, in a preregistered longitudinal study, we investigated whether 30 d of guided mindfulness meditation using a mobile application improved attentional control measured with eye movements. We hypothesized that older adults would show greater benefits from the mindfulness intervention compared with young adults. In two oculomotor search tasks, we identifie...

Introduction. Alzheimer's disease (AD) is the most common cause of dementia, where substantial neuronal loss and neuropathological lesions can damage many brain regions, symptoms of the disease begin with mild memory difficulties and evolve towards cogn...

Why we sleep remains one of science’s greatest unsolved mysteries. However, researchers are beginning to unravel and understand the intricate neurobiological mechanisms involved in the process of sleep.

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Our analysis of a simple stiffness control during quiet standing (winter, et al. 1998) has been challenged by Morasso and Schieppati (1999). They claim that the centre of pressure (COP) will automatically be in phase with the centre of mass (COM) as a necessary consequence of physical laws. However, their arguments and control model ignore the afferent and efferent delays characteristic of all reactive control in many reports in the literature. They also claim that the magnitude of spring stiffness must be well in excess of the gravitational spring, mgh, but their assumption of white noise and spike noise at the muscle level is not valid. Our analysis of the noise at the muscle level revealed that it was a low frequency ripple due to the summation of twitches and it was less than 2% of the muscle tone. Also, their review of stiffness measures in the literature was flawed and our reassessment of their references demonstrates ankle stiffness to be close to the measures reported by Winter, et al. (1998) in sp...

While the literature has long established the relationship between the environment and mental health, less is known about the neural correlates underlying these associations. Emotion-related disorders, such as anxiety, commonly begin during childhood an...

Humans can adapt their movements in response to expected and unexpected perturbations. The speed and accuracy of these movement corrections may depend on the type of sensory information driving the perception of these perturbations. While previous research has indicated that corrections based on somatosensory information, comprised of proprioceptive and tactile inputs, are faster than corrections based on visual information, other studies have found comparable correction speeds in response to visual and tactile inputs. The purpose of this study was to systematically investigate the latencies (how fast) and magnitudes (how large) of movement corrections in response to perturbations of external visual targets, as well as somatosensory (proprioceptive and tactile) and tactile targets on the non-reaching limb. Participants performed reaching movements to a light-emitting diode (i.e., visual target), the felt position of a brush touching the index finger of the non-reaching hand (i.e., a tactile target), and th...

Spike and wave discharges (SWD), generated by the cortico-thalamo-cortical (CTC) network, are pathological oscillations and the hallmark of absence seizures. SWD begin in cortical initiation networks in both humans and animal models, including the Genet...

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