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When the eyes are fixated on a spot, fixation neurons in the frontal eye field (FEF) show an increase in activity. Our previous study suggested that fixation neurons in the FEF contribute to the suppression of saccades and smooth pursuit eye movements to maintain active fixation. The present study examined the role of the FEF in the suppressive control of reflexive eye movements, optokinetic and vestibular nystagmus, in trained monkeys. Electrical stimulation in the FEF suppressed the quick and slow phases of optokinetic and vestibular nystagmus at an intensity lower than the threshold for eliciting electrically evoked saccades. Relatively weak suppression influenced the slow phase of vestibular nystagmus. During optokinetic or vestibular nystagmus, presentation of a stationary small spot to the eyes followed by fixation is known to suppress both the quick and slow phases of eye movements. We recorded the activity of fixation neurons in the FEF and found that fixation neurons usually showed a decrease in activity during optokinetic and vestibular nystagmus and an increase in activity during the suppression of nystagmus by visual fixation. The present results show that the activity of fixation neurons in the FEF is related to the suppressive control of optokinetic and vestibular nystagmus for maintaining active fixation. We discuss the role of a generalized visual fixation system that can maintain visual attention on an interesting object. NEW & NOTEWORTHY In this study, electrical stimulation in the frontal eye field (FEF) suppressed the quick and slow phases of optokinetic and vestibular nystagmus at an intensity subthreshold for eliciting saccades. Furthermore, the activity of fixation neurons in the FEF was related to the suppression of optokinetic and vestibular nystagmus by visual fixation. This suggests that a common neuronal assembly in the FEF may contribute to the suppressive control of different functional classes of eye movements.

We recorded the activity of fixation neurons in the frontal eye field (FEF) in trained monkeys and analyzed their activity during smooth pursuit eye movements. Fixation neurons were densely located in the area of the FEF in the caudal part of the arcuate gyrus facing the inferior arcuate sulcus where focal electrical stimulation suppressed the generation of saccades and smooth pursuit in bilateral directions at an intensity lower than the threshold for eliciting electrically evoked saccades. Whereas fixation neurons discharged tonically during fixation, they showed a variety of discharge patterns during smooth pursuit, ranging from a decrease in activity to an increase in activity. Of these, more than two-thirds were found to show a reduction in activity during smooth pursuit in the ipsilateral and bilateral directions. The reduction in activity of fixation neurons began at pursuit initiation and continued during pursuit maintenance. When catch-up saccades during the initiation of pursuit were eliminated by a step-ramp target routine, the reduced activity of fixation neurons remained. The reduction in activity during pursuit was not dependent on the activity during fixation without a target. Based on these results, we discuss the role of the FEF at maintaining fixation in relation to various other brain areas. We suggest that fixation neurons in the FEF contribute to the suppression of smooth pursuit. These results suggest that FEF fixation neurons are part of a more generalized visual fixation system through which suppressive control is exerted on smooth pursuit, as well as saccades., (Copyright © 2014 the American Physiological Society.)

Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists play important roles in the regulation of energy metabolism and are widely used for patients with type 2 diabetes. PPARgamma agonists reportedly reduce plasma glucose levels by recruiting glucose transporters to the cellular membrane, resulting in the enhanced uptake of glucose. However, only a limited number of studies have examined the effect of PPARgamma on cerebral glucose metabolism. In the present study, we examined the effects of a PPARgamma agonist, pioglitazone, on glucose metabolism in cultured rat neurons and astroglia. Cultures of neurons or astroglia were prepared from Sprague-Dawley rats. The cells were treated with pioglitazone (0-50 muM) for 48 hours prior to assay. Lactate released into the culture medium (an index of glycolytic glucose metabolism) and [U-(14)C]lactate or [1-(14)C]pyruvate oxidation (an index of oxidative glucose metabolism) were measured. In addition, the production of cellular reactive oxygen species (ROS) was determined utilizing an H(2)DCFDA assay. Forty-eight hours of exposure to pioglitazone (0.5 and 5 muM) resulted in dose-dependent increases in lactate release into the astroglial culture medium but not into the neuronal culture medium. [U-(14)C]lactate oxidation and [1-(14)C]pyruvate oxidation were enhanced in the neurons, but not in the astroglia. These actions of pioglitazone were not inhibited by 2-chloro-5-nitrobenzanilide (GW9662), a potent antagonist of PPARgamma, and were not mimicked by N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino)ethyl]-l-tyrosine (GW1929), a non-thiazolidinedione PPARgamma agonist. Pioglitazone enhanced aerobic glycolysis and lactate release in astroglia, while the oxidative metabolism of glucose, but not glycolysis, was augmented in neurons without increasing ROS production. These results indicate that pioglitazone may enhance the efficiency of glucose metabolism in the brain.

Electrical stimulation of the frontal eye field (FEF) has recently been reported to suppress the generation of saccades, which supports the idea that the FEF plays a role in maintaining attentive fixation. This study analyzed the activity of fixation neurons that discharged during fixation in the FEF in relation to visual fixation and saccades in trained monkeys. The neural activity of fixation neurons increased at the start of fixation and was maintained during fixation. When a fixation spot of light disappeared during steady fixation, different fixation neurons exhibited different categories of response, ranging from a decrease in activity to an increase in activity, indicating that there is a continuum of fixation neurons, from neurons with foveal visual-related activity to neurons with activity that is related to the motor act of fixating. Fixation neurons usually showed a decrease in their firing rate before the onset of visually guided saccades (Vsacs) and memory-guided saccades in any direction. The reduction in activity of fixation neurons nearly coincided with, or occurred slightly before, the increase in the activity of saccade-related movement neurons in the FEF in the same monkey. Although fixation neurons were scattered in the FEF, about two thirds of fixation neurons were concentrated in a localized area in the FEF at which electrical stimulation induced strong suppression of the initiation of Vsacs bilaterally. These results suggest that fixation neurons in the FEF are part of a suppression mechanism that could control the maintenance of fixation and the initiation of saccades.

Previous electrophysiological studies have shown that the commissural connections between the two superior colliculi are mainly inhibitory with fewer excitatory connections. However, the functional roles of the commissural connections are not well understood, so we sought to clarify the physiology of tectal commissural excitation and inhibition of tectoreticular neurons (TRNs) in the "fixation " and "saccade " zones of the superior colliculus (SC). By recording intracellular potentials, we identified TRNs by their antidromic responses to stimulation of the omnipause neuron (OPN) and inhibitory burst neuron (IBN) regions and analyzed the effects of stimulation of the contralateral SC on these TRNs in anesthetized cats. TRNs in the caudal SC (saccade neurons) projected to the IBN region, and received mono- or disynaptic inhibition from the entire rostrocaudal extent of the contralateral SC. In contrast, TRNs in the rostral SC projected to the OPN or IBN region and received monosynaptic excitation from the most rostral level of the contralateral SC, and mono- or disynaptic inhibition from its entire rostrocaudal extent. Among the rostral TRNs with commissural excitation, IBN-projecting TRNs also projected to Forel's field H (vertical gaze center), suggesting that they were most likely saccade neurons related to vertical saccades. In contrast, TRNs projecting only to the OPN region were most likely fixation neurons. Most putative inhibitory neurons in the rostral SC had multiple axon branches throughout the rostrocaudal extent of the contralateral SC, whereas excitatory commissural neurons, most of which were rostral TRNs, distributed terminals to a discrete region in the rostral SC.

The caudal part of the superior colliculus (SC) plays an important role in the generation of saccades, whereas the rostral part of the SC is considered to be involved in visual fixation. The present study was performed to determine neural connections from the rostral and caudal parts of the SC to inhibitory burst neurons (IBNs) and pause neurons (PNs) in the nucleus raphe interpositus in the anesthetized cat, and to reveal the functional role of the rostral SC on eye movements. The intracellular potentials from IBNs and PNs were recorded, and the effects of stimulation of the SC on these neurons were analyzed. The results show that IBNs receive monosynaptic excitation from the contralateral caudal SC, and disynaptic inhibition from the ipsilateral caudal SC via contralateral IBNs. In addition, IBNs receive disynaptic inhibition from the rostral part of the SC on either side via inhibitory interneurons other than IBNs. Intracellular recording from PNs revealed that they receive convergent excitation from the rostral parts of the bilateral superior colliculi and that the rostral SC inhibits IBNs on both sides via PNs. The neural connections determined in this study support the functional independence of the rostral SC and are consistent with the notion that the "fixation zone" is localized in the rostral SC. These results show that the fixation zone in the rostral SC may suppress the initiation of bilateral saccades via pause neurons.

Vestibular input to the periarcuate cortex in the Japanese monkey was examined by analyzing laminar field potentials evoked by electrical stimulation of the vestibular nerve. Vestibular-evoked potentials consisted of early-positive and late-negative potentials and early-negative and late-positive potentials in the superficial and deep layers of the cortex, respectively. They were distributed bilaterally in the periarcuate cortex around the junction of the spur and the arcuate sulcus. This vestibular-projecting area corresponded to the periarcuate area where retrogradely-labeled corticovestibular neurons were distributed after the injection of a tracer into the vestibular nuclei. Comparison of the vestibular-projection area with the distribution of smooth pursuit-related neurons in the same monkey revealed that such neurons existed in the vestibular-projecting area of the periarcuate cortex.

The caudal superior colliculus (SC) contains movement neurons that fire during saccades and the rostral SC contains fixation neurons that fire during visual fixation, suggesting potentially different functions for these 2 regions. To study whether these areas might have different projections, we characterized synaptic inputs from the rostral and caudal SC to inhibitory burst neurons (IBNs) in anesthetized cats. We recorded intracellular potentials from neurons in the IBN region and identified them as IBNs based on their antidromic activation from the contralateral abducens nucleus and short-latency excitation from the contralateral caudal SC and/or single-cell morphology. IBNs received disynaptic inhibition from the ipsilateral caudal SC and disynaptic inhibition from the rostral SC on both sides. Stimulation of the contralateral IBN region evoked monosynaptic inhibition in IBNs, which was enhanced by preconditioning stimulation of the ipsilateral caudal SC. A midline section between the IBN regions eliminated inhibition from the ipsilateral caudal SC, but inhibition from the rostral SC remained unaffected, indicating that the latter inhibition was mediated by inhibitory interneurons other than IBNs. A transverse section of the brain stem rostral to the pause neuron (PN) region eliminated inhibition from the rostral SC, suggesting that this inhibition is mediated by PNs. These results indicate that the most rostral SC inhibits bilateral IBNs, most likely via PNs, and the more caudal SC exerts monosynaptic excitation on contralateral IBNs and antagonistic inhibition on ipsilateral IBNs via contralateral IBNs. The most rostral SC may play roles in maintaining fixation by inhibition of burst neurons and facilitating saccadic initiation by releasing their inhibition.

Rats showing an ataxic gait induced by 20 wk of treatment with 0, 30, or 60 mg/kg of difluorobenzhydrylpiperadine (DFBP), a detriazinyl metabolic of almitrine, were examined by light microscopy and transmission electron microscopy. Vacuolar degeneration associated with lamellar inclusions was observed in musculus soleus and m. interossei of the hindlimbs in DFBP-treated rats. The inclusions were also produced within sensory neurons, satellite and Schwann cells, and vascular endothelial cells of thoracic and lumbar dorsal root ganglia as well as muscle spindles of affected muscles. Membrane-bound vacuoles containing electron-dense granules were seen in the peripheral nerves. This study demonstrated neuronal and muscular toxicity of DFBP in rats.