Light adaptation in the chick retina: Dopamine, nitric oxide, and gap-junction coupling modulate spatiotemporal contrast sensitivity.

Adaptation to changes in ambient light intensity, in retinal cells and circuits, optimizes visual functions. In the retina, light-adaptation results in changes in light-sensitivity and spatiotemporal tuning of ganglion cells. Under light-adapted conditions, contrast sensitivity (CS) of ganglion cells is a bandpass function of spatial frequency; in contrast, dark-adaptation reduces CS, especially at higher spatial frequencies. In this work, we aimed to understand intrinsic neuromodulatory mechanisms that underlie retinal adaptation to changes in ambient light level. Specifically, we investigated how CS is affected by dopamine (DA), nitric oxide (NO), and modifiers of electrical coupling through gap junctions, under different conditions of adapting illumination. Using the optokinetic response as a behavioral readout of direction-selective ganglion cell activity, we characterized the spatial CS of chicks under high- and low-photopic conditions and how it was regulated by DA, NO, and gap-junction uncouplers. We observed that: (1) DA D2R-family agonists and a donor of NO increased CS tested in low-photopic illumination, as if observed in the high-photopic light; whereas (2) removing their effects using either DA antagonists or NO- synthase inhibitors mimicked low-photopic CS; (3) simulation of high-photopic CS by DA agonists was abolished by NO-synthase inhibitors; and (4) selectively blocking coupling via connexin 35/36-containing gap junctions, using a "designer" mimetic peptide, increased CS, as does strong illumination. We conclude that, in the chicken retina: (1) DA and NO induce changes in spatiotemporal processing, similar to those driven by increasing illumination, (2) DA possibly acts through stimulating NO synthesis, and (3) blockade of coupling via gap junctions containing connexin 35/36 also drives a change in retinal CS functions. As a noninvasive method, the optokinetic response can provide rapid, conditional, and reversible assessment of retinal functions when pharmacological reagents are injected into the vitreous humor. Finally, the chick's large eyes, and the many similarities between their adaptational circuit functions and those in mammals such as the mouse, make them a promising model for future retinal research.

Early Intensive Leg Training to Enhance Walking in Children With Perinatal Stroke: Protocol for a Randomized Controlled Trial.

BACKGROUND: Development of motor pathways is modulated by activity in these pathways, when they are maturing (ie, critical period). Perinatal stroke injures motor pathways, including the corticospinal tracts, reducing their activity and impairing motor function. Current intervention for the lower limb emphasizes passive approaches (stretching, braces, botulinum toxin injections). The study hypothesis was that intensive, early, child-initiated activity during the critical period will enhance connectivity of motor pathways to the legs and improve motor function. OBJECTIVE: The study objective was to determine whether early intervention with intensive activity is better than standard care, intervention delivered during the proposed critical period is better than after, and the outcomes are different when the intervention is delivered by a physical therapist in an institution vs. a parent at home. DESIGN: A prospective, delay-group, single-blind, randomized controlled trial (RCT) and a parallel, cohort study of children living beyond commuting distance and receiving an intervention delivered by their parent. SETTING: The RCT intervention was provided in university laboratories, and parent training was provided in the childs home. PARTICIPANTS: Children 8 months to 3 years old with MRI-confirmed perinatal ischemic stroke and early signs of hemiparesis. INTERVENTION: Intensive, play-based leg activity with weights for the affected leg and foot, 1 hour/day, 4 days/week for 12 weeks. MEASUREMENTS: The primary outcome was the Gross Motor Function Measure-66 score. Secondary outcomes were motion analysis of walking, full-day step counts, motor evoked potentials from transcranial magnetic stimulation, and patellar tendon reflexes. LIMITATIONS: Inter-individual heterogeneity in the severity of the stroke and behavioral differences are substantial but measurable. Differences in intervention delivery and assessment scoring are minimized by standardization and training. CONCLUSIONS: The intervention, contrary to current practice, could change physical therapy interventions for children with perinatal stroke.

Neuronal expression of the intermediate conductance calcium-activated potassium channel KCa3.1 in the mammalian central nervous system.

The expression pattern and functional roles for calcium-activated potassium channels of the KCa2.x family and KCa1.1 have been extensively examined in central neurons. Recent work indicates that intermediate conductance calcium-activated potassium channels (KCa3.1) are also expressed in central neurons of the cerebellum and spinal cord. The current study used immunocytochemistry and GFP linked to KCNN4 promoter activity in a transgenic mouse to determine the expression pattern of KCa3.1 channels in rat or mouse neocortex, hippocampus, thalamus, and cerebellum. KCa3.1 immunolabel and GFP expression were closely matched and detected in both excitatory and inhibitory cells of all regions examined. KCa3.1 immunolabel was localized primarily to the somatic region of excitatory cells in cortical structures but at the soma and over longer segments of dendrites of cells in deep cerebellar nuclei. More extensive labeling was apparent for inhibitory cells at the somatic and dendritic level with no detectable label associated with axon tracts or regions of intense synaptic innervation. The data indicate that KCa3.1 channels are expressed in the CNS with a differential pattern of distribution between cells, suggesting important functional roles for these calcium-activated potassium channels in regulating the excitability of central neurons.