In vivo MRI evaluation of anterograde manganese transport along the visual pathway following whole eye transplantation.

BACKGROUND: Since adult mammalian retinal ganglion cells cannot regenerate after injury, we have recently established a whole-eye transplantation (WET) rat model that provides an intact optical system to investigate potential surgical restoration of irreversible vision loss. However, it remains to be elucidated whether physiological axoplasmic transport exists in the transplanted visual pathway. NEW METHOD: We developed an in vivo imaging model system to assess WET integration using manganese-enhanced magnetic resonance imaging (MEMRI) in rats. Since Mn2+ is a calcium analogue and an active T1-positive contrast agent, the levels of anterograde manganese transport can be evaluated in the visual pathways upon intravitreal Mn2+ administration into both native and transplanted eyes. RESULTS: No significant intraocular pressure difference was found between native and transplanted eyes, whereas comparable manganese enhancement was observed between native and transplanted intraorbital optic nerves, suggesting the presence of anterograde manganese transport after WET. No enhancement was detected across the coaptation site in the higher visual areas of the recipient brain. COMPARISON WITH EXISTING METHODS: Existing imaging methods to assess WET focus on either the eye or local optic nerve segments without direct visualization and longitudinal quantification of physiological transport along the transplanted visual pathway, hence the development of in vivo MEMRI. CONCLUSION: Our established imaging platform indicated that essential physiological transport exists in the transplanted optic nerve after WET. As neuroregenerative approaches are being developed to connect the transplanted eye to the recipient's brain, in vivo MEMRI is well-suited to guide strategies for successful WET integration for vision restoration.

Selective serotonin receptor stimulation of the ventral tegmentum differentially affects appetitive motivation for sugar on a progressive ratio schedule of reinforcement.

Serotonin signaling influences satiety and motivation through known actions in the hindbrain and hypothalamus. Recently, we reported that some classes of serotonin receptors also modulate food intake through actions in the ventral tegmentum and the nucleus accumbens. In the current experiments, we examined whether activation or blockade of individual serotonin receptor subtypes in the ventral tegmentum might also affect appetitive motivation for sugar pellets as assessed in a progressive ratio (PR) task. Separate groups of rats were tested following stimulation or blockade of ventral tegmental serotonin 1A, 1B, 2A, 2B, 2C, or 3 receptors. Rats within each group received multiple doses of a single drug across days; each test was separated by 72 h. Progressive ratio break point was significantly affected by stimulation of ventral tegmental serotonin 1A receptors with 8-OH-DPAT (0, 2, 4, 8 µg/side) or stimulation of serotonin 3 receptors with mCPBG (0, 10, & 20 µg/side). High doses of both agents tended to decrease break point. Additionally, stimulation of serotonin 2C receptors with RO60-0175 (at 0, 2, and 5 µg/side) reduced total lever presses and demonstrated a trend towards reducing break point. There were no effects of stimulating ventral tegmental serotonin 1B, 2A, or 2B receptors on break point; neither did antagonism of any of the serotonin receptor subtypes significantly affect performance. These data provide additional evidence that serotonergic signaling in the mesolimbic pathway affects motivated behavior, and demonstrate that a subset of serotonin receptors impact not only food consumption, but appetitive food-seeking as well.

The effects of chloride dynamics on substantia nigra pars reticulata responses to pallidal and striatal inputs.

As a rodent basal ganglia (BG) output nucleus, the substantia nigra pars reticulata (SNr) is well positioned to impact behavior. SNr neurons receive GABAergic inputs from the striatum (direct pathway) and globus pallidus (GPe, indirect pathway). Dominant theories of action selection rely on these pathways' inhibitory actions. Yet, experimental results on SNr responses to these inputs are limited and include excitatory effects. Our study combines experimental and computational work to characterize, explain, and make predictions about these pathways. We observe diverse SNr responses to stimulation of SNr-projecting striatal and GPe neurons, including biphasic and excitatory effects, which our modeling shows can be explained by intracellular chloride processing. Our work predicts that ongoing GPe activity could tune the SNr operating mode, including its responses in decision-making scenarios, and GPe output may modulate synchrony and low-frequency oscillations of SNr neurons, which we confirm using optogenetic stimulation of GPe terminals within the SNr.

Unusual Volar Pulp Location of Glomus Tumor.

Glomus tumors are benign, painful growths originating from glomus bodies and comprise just 1% of tumors arising in the hand, with fewer than 10% in the volar pulp of digits. Hallmark symptoms of glomus tumors include hypersensitivity to cold, heightened pinprick sensitivity, and paroxysmal pain. We report a 72-year-old, right-hand dominant man who presented with pain in the left middle finger, localized to the tip. The fingertip was incredibly sensitive to touch, and his pain increased at night. He reported no recollection of trauma. Palpation of the finger revealed no mass, although it did indicate a focal point of pain within the distal pulp of the digit. Magnetic resonance imaging of the left hand revealed a round 7.0 × 4.0 × 6.0-mm soft tissue lesion along the volar ulnar aspect of the distal third digit. An incision was made in the mid-axial plane, circumscribing and removing the mass bluntly. It was a tan-yellow, soft tissue nodule of 0.8-cm in diameter without stalk or adherences to joints. Pathology revealed the mass was a glomus tumor. Symptoms improved on removal, and he healed without complication. Glomus tumors in the volar digital pulp can be difficult to diagnose. However, the presence of localized pain in the fingertip was reason to consider glomus tumor and proceed with treatment. Complete surgical removal of a glomus tumor is necessary to resolve symptoms and prevent recurrence.

A systematic investigation of the differential roles for ventral tegmentum serotonin 1- and 2-type receptors on food intake in the rat.

Central serotonin (5-HT) pathways are known to influence feeding and other ingestive behaviors. Although the ventral tegmentum is important for promoting the seeking and consumption of food and drugs of abuse, the roles of 5-HT receptor subtypes in this region on food intake have yet to be comprehensively examined. In these experiments, food restricted rats were given 2-h access to rat chow; separate groups of non-restricted animals had similar access to a sweetened fat diet. Feeding and locomotor activity were monitored following ventral tegmentum stimulation or blockade of 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, or 5-HT2C receptors. 5-HT1A receptor stimulation transiently inhibited rearing behavior and chow intake in food-restricted rats, and had a biphasic effect on non-restricted rats offered the palatable diet. 5-HT1B receptor agonism transiently inhibited feeding in restricted animals, but did not affect intake of non-restricted rats. In contrast, 5-HT1B receptor antagonism decreased palatable feeding. Although stimulation of ventral tegmental 5-HT2B receptors with BW723C86 did not affect hunger-driven food intake, it significantly affected palatable feeding, with a trend for an increasing intake at 2.0µg/side but not at 5.0µg/side. Antagonism of the same receptor modestly but significantly inhibited feeding of the palatable diet at 5.0µg/side ketanserin. Neither stimulation nor blockade of 5-HT2A or 5-HT2C receptors caused prolonged effects on intake or locomotion. These data suggest that serotonin's effects on feeding within the ventral tegmentum depend upon the specific receptor targeted, as well as whether intake is motivated by food restriction or the palatable nature of the offered diet.