Chemotherapy-induced peripheral neuropathy (CIPN) affects ∼68% of patients undergoing chemotherapy, causing debilitating neuropathic pain and reducing quality of life. Cisplatin is a commonly used platinum-based chemotherapeutic drug known to cause CIPN, possibly by causing oxidative stress damage to primary sensory neurons. Metabotropic glutamate receptors (mGluRs) are widely hypothesized to be involved in pain processing and pain mitigation. Meclizine is an H1 histamine receptor antagonist known to have neuroprotective effects, including an anti-oxidative effect. Here, we used a mouse model of cisplatin-induced CIPN using male and female mice to test agonists of mGluR8 and Group II mGluR as well as meclizine as interventions to reduce cisplatin-induced pain. We performed behavioral pain tests, and we imaged Ca2+ activity of the large population of dorsal root ganglia (DRG) neurons in vivo . For the latter, we used a genetically-encoded Ca2+ indicator, Pirt-GCaMP3, which enabled us to monitor different dr...

During development, critical periods of synaptic plasticity facilitate the reordering and refinement of neural connections, allowing the definitive synaptic circuits responsible for correct adult physiology to be established. The L4–L2/3 synapses in the somatosensory cortex (S1) exhibit a presynaptic form of spike timing-dependent long-term depression (t-LTD) that probably fulfills a role in synaptic refinement. This t-LTD persists until the fourth postnatal week in mice, disappearing thereafter. When we investigated the mechanisms underlying this maturation-related loss of t-LTD in either sex mouse slices, we found that it could be completely recovered by antagonizing adenosine type 1 receptors. By contrast, an agonist of A1R impeded the induction of t-LTD at P13–27. Furthermore, we found that the adenosine that mediated the loss of t-LTD at the end of the fourth week of development is most probably supplied by astrocytes. At more mature stages (P38–60), we found that the protocol used to induce t-LTD pro...

Foraging entails a complex balance between approach and avoidance alongside sensorimotor and homeostatic processes under the control of multiple cortical and subcortical areas. Recently, it has become clear that several thalamic nuclei located near the midline regulate motivated behaviors. However, one midline thalamic nucleus that projects to key nodes in the foraging network, the central medial thalamic nucleus (CMT), has received little attention so far. Therefore, the present study examined CMT contributions to foraging behavior using inactivation and unit recording techniques in male rats. Inactivation of CMT or the basolateral amygdala (BLA) with muscimol abolished the normally cautious behavior of rats in the foraging task. Moreover, CMT neurons showed large but heterogeneous activity changes during the foraging task, with many neurons decreasing or increasing their discharge rates, with a modest bias for the latter. A generalized linear model revealed that the nature (inhibitory vs excitatory) and ...

Altered amygdala development is implicated in the neurobiology of autism, but little is known about the coordinated development of the brain regions directly connected with the amygdala. Here we investigated the volumetric development of an amygdala-connected network, defined as the set of brain regions with monosynaptic connections with the amygdala, in autism from early to middle childhood. A total of 950 longitudinal structural MRI scans were acquired from 282 children (93 female) with autism and 128 children with typical development (61 female) at up to four time points (mean ages: 39, 52, 64, and 137 months, respectively). Volumes from 32 amygdala-connected brain regions were examined using mixed effects multivariate distance matrix regression. The Social Responsiveness Scale-2 was administered to assess degree of autistic traits and social impairments. The amygdala-connected network exhibited persistent diagnostic differences ( p values ≤ 0.03) that increased over time ( p values ≤ 0.02). These diffe...

A pioneering study by [Volkmann (1858)][1] revealed that training on a tactile discrimination task improved task performance, indicative of tactile learning, and that such tactile learning transferred from trained to untrained body parts. However, the neural mechanisms underlying tactile learning and transfer of tactile learning have remained unclear. We trained groups of human subjects (female and male) in daily sessions on a tactile discrimination task either by stimulating the palm of the right hand or the sole of the right foot. Task performance before training was similar between the palm and sole. Posttraining transfer of tactile learning was greater from the trained right sole to the untrained right palm than from the trained right palm to the untrained right sole. Functional magnetic resonance imaging (fMRI) and multivariate pattern classification analysis revealed that the somatotopic representation of the right palm in contralateral primary somatosensory cortex (SI) was coactivated during tactile...

Irene Martínez-Gallego, Mikel Pérez-Rodríguez, Heriberto Coatl-Cuaya, Gonzalo Flores, and Antonio Rodríguez-Moreno (see pages [6038–6052][1]) During nervous system development, an initial period of prolific synaptogenesis is followed by a period of enhanced plasticity, in which synapses are

Before visual information from the retina reaches primary visual cortex, it is dynamically filtered by the lateral geniculate nucleus (LGN) of the thalamus, the first location within the visual hierarchy at which non-retinal structures can significantly influence visual processing. To explore the form and dynamics of geniculate filtering we used data from monosynpatically connected pairs of retinal ganglion cells (RGCs) and LGN relay cells in the cat that, under anesthetized conditions, were stimulated with binary white noise and/or drifting sine-wave gratings to train models of increasing complexity to predict which RGC spikes were relayed to cortex, what we call “relay status”. In addition, we analyze and compare a smaller data set recorded in the awake state to assess how anesthesia might influence our results. Consistent with previous work, we find that the preceding retinal inter-spike interval is the primary determinate of relay status with only modest contributions from longer patterns of retinal sp...

We tested the hypothesis that the pallidum contributes to the control of both posture and movement. We recorded neuronal activity from the pallidum in a task in which male cats reached forward from a standing posture to depress a lever. In agreement with previous studies, we found that a majority of pallidal cells (91/116, 78%), including neurons in both the entopeduncular nucleus and the globus pallidus, showed significant modulation of their activity during reaching with the contralateral limb. Mostly different populations of cells were active during the transport (flexion) and lever press (extension) phase of the task. Most cells showed dynamic patterns of activity related to the movement. However, a modest proportion of modulated cells (18/91, 20%) showed properties consistent with a contribution to the control of anticipatory postural responses, whereas a further 10% showed activity consistent with a contribution to postural support during the movement. Although some cells that showed modified activit...

Experiences of physical exertion guide our assessments of effort. While these assessments critically influence our decisions to engage in daily activities, little is known about how they are generated. We had female and male human participants exert grip force and assess how effortful these exertions felt; and used magnetic resonance spectroscopy to measure their brain GABA concentration. We found that variability in exertion (i.e., the coefficient of variation in their force exertion profile) was associated with increases in assessments of effort, making participants judge efforts as more costly. GABA levels in the sensorimotor cortex (SM1) moderated the influence of exertion variability on overassessments of effort. In individuals with higher sensorimotor GABA, exertion variability had a diminished influence on overassessments of effort. Essentially, sensorimotor GABA had a protective effect on the influence of exertion variability on inflations of effort assessment. Our findings provide a neurobiologica...