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David M Lasker - One of the best experts on this subject based on the ideXlab platform.
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horizontal vestibuloocular reflex evoked by high acceleration rotations in the squirrel monkey iii responses after labyrinthectomy
Journal of Neurophysiology, 2000Co-Authors: David M Lasker, Timothy E Hullar, Lloyd B MinorAbstract:The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral labyrinthectomy. Spontaneous nystagmus was measured at the beginning and end of each testing session. During the period that animals were kept in darkness (4 days), the nystagmus at each of these times measured approximately 20 degrees /s. Within 18-24 h after return to the light, the nystagmus (measured in darkness) decreased to 2.8 +/- 1.5 degrees /s (mean +/- SD) when recorded at the beginning but was 20.3 +/- 3.9 degrees /s at the end of the testing session. The latency of the VOR measured from responses to steps of acceleration (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) was 8.4 +/- 0.3 ms for responses to ipsilesional rotations and 7.7 +/- 0.4 ms for contralesional rotations. During the period that animals were kept in darkness after the labyrinthectomy, the gain of the VOR measured during the steps of acceleration was 0.67 +/- 0.12 for contralesional rotations and 0.39 +/- 0.04 for ipsilesional rotations. Within 18-24 h after return to light, the VOR gain for contralesional rotations increased to 0.87 +/- 0.08, whereas there was only a slight increase for ipsilesional rotations to 0.41 +/- 0. 06. A symmetrical increase in the gain measured at the plateau of head velocity was noted after the animals were returned to light. The VOR evoked by sinusoidal rotations of 2-15 Hz, +/-20 degrees /s, showed a better recovery of gain at lower (2-4 Hz) than at higher (6-15 Hz) frequencies. At 0.5 Hz, gain decreased symmetrically when the peak amplitude was increased from 20 to 100 degrees /s. At 10 Hz, gain was decreased for ipsilesional half-cycles and increased for contralesional half-cycles when velocity was raised from 20 to 50 degrees /s. A model incorporating Linear and nonLinear Pathways was used to simulate the data. Selective increases in the gain for the Linear Pathway accounted for the recovery in VOR gain for responses at the velocity plateau of the steps of acceleration and for the sinusoidal rotations at lower peak velocities. The increase in gain for contralesional responses to steps of acceleration and sinusoidal rotations at higher frequencies and velocities was due to an increase in the contribution of the nonLinear Pathway. This Pathway was driven into cutoff and therefore did not affect responses for rotations toward the lesioned side.
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Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. I. Normal responses.
Journal of neurophysiology, 1999Co-Authors: David M Lasker, Douglas D. Backous, Timothy E HullarAbstract:The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in five squirrel monkeys with intact vestibular function. The VOR evoked by steps of acceleration in darkness (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) began after a latency of 7.3 +/- 1.5 ms (mean +/- SD). Gain of the reflex during the acceleration was 14.2 +/- 5.2% greater than that measured once the plateau head velocity had been reached. A polynomial regression was used to analyze the trajectory of the responses to steps of acceleration. A better representation of the data was obtained from a polynomial that included a cubic term in contrast to an exclusively Linear fit. For sinusoidal rotations of 0.5-15 Hz with a peak velocity of 20 degrees /s, the VOR gain measured 0.83 +/- 0.06 and did not vary across frequencies or animals. The phase of these responses was close to compensatory except at 15 Hz where a lag of 5.0 +/- 0.9 degrees was noted. The VOR gain did not vary with head velocity at 0.5 Hz but increased with velocity for rotations at frequencies of >/=4 Hz (0. 85 +/- 0.04 at 4 Hz, 20 degrees /s; 1.01 +/- 0.05 at 100 degrees /s, P < 0.0001). No responses to these rotations were noted in two animals that had undergone bilateral labyrinthectomy indicating that inertia of the eye had a negligible effect for these stimuli. We developed a mathematical model of VOR dynamics to account for these findings. The inputs to the reflex come from Linear and nonLinear Pathways. The Linear Pathway is responsible for the constant gain across frequencies at peak head velocity of 20 degrees /s and also for the phase lag at higher frequencies being less than that expected based on the reflex delay. The frequency- and velocity-dependent nonLinearity in VOR gain is accounted for by the dynamics of the nonLinear Pathway. A transfer function that increases the gain of this Pathway with frequency and a term related to the third power of head velocity are used to represent the dynamics of this Pathway. This model accounts for the experimental findings and provides a method for interpreting responses to these stimuli after vestibular lesions.
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horizontal vestibuloocular reflex evoked by high acceleration rotations in the squirrel monkey ii responses after canal plugging
Journal of Neurophysiology, 1999Co-Authors: David M Lasker, Douglas D. Backous, Anna Lysakowski, Griffin L Davis, Lloyd B MinorAbstract:The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral plugging of the three semicircular canals. During the period (1-4 days) that animals were kept in darkness after plugging, the gain during steps of acceleration (3, 000 degrees /s(2), peak velocity = 150 degrees /s) was 0.61 +/- 0.14 (mean +/- SD) for contralesional rotations and 0.33 +/- 0.03 for ipsilesional rotations. Within 18-24 h after animals were returned to light, the VOR gain for contralesional rotations increased to 0. 88 +/- 0.05, whereas there was only a slight increase in the gain for ipsilesional rotations to 0.37 +/- 0.07. A symmetrical increase in the gain measured at the plateau of head velocity was noted after animals were returned to light. The latency of the VOR was 8.2 +/- 0. 4 ms for ipsilesional and 7.1 +/- 0.3 ms for contralesional rotations. The VOR evoked by sinusoidal rotations of 0.5-15 Hz, +/-20 degrees /s had no significant half-cycle asymmetries. The recovery of gain for these responses after plugging was greater at lower than at higher frequencies. Responses to rotations at higher velocities for frequencies >/=4 Hz showed an increase in contralesional half-cycle gain, whereas ipsilesional half-cycle gain was unchanged. A residual response that appeared to be canal and not otolith mediated was noted after plugging of all six semicircular canals. This response increased with frequency to reach a gain of 0.23 +/- 0.03 at 15 Hz, resembling that predicted based on a reduction of the dominant time constant of the canal to 32 ms after plugging. A model incorporating Linear and nonLinear Pathways was used to simulate the data. The coefficients of this model were determined from data in animals with intact vestibular function. Selective increases in the gain for the Linear and nonLinear Pathways predicted the changes in recovery observed after canal plugging. An increase in gain of the Linear Pathway accounted for the recovery in VOR gain for both responses at the velocity plateau of the steps of acceleration and for the sinusoidal rotations at lower peak velocities. The increase in gain for contralesional responses to steps of acceleration and sinusoidal rotations at higher frequencies and velocities was due to an increase in the gain of the nonLinear Pathway. This Pathway was driven into inhibitory cutoff at low velocities and therefore made no contribution for rotations toward the ipsilesional side.
Lloyd B Minor - One of the best experts on this subject based on the ideXlab platform.
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horizontal vestibuloocular reflex evoked by high acceleration rotations in the squirrel monkey iii responses after labyrinthectomy
Journal of Neurophysiology, 2000Co-Authors: David M Lasker, Timothy E Hullar, Lloyd B MinorAbstract:The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral labyrinthectomy. Spontaneous nystagmus was measured at the beginning and end of each testing session. During the period that animals were kept in darkness (4 days), the nystagmus at each of these times measured approximately 20 degrees /s. Within 18-24 h after return to the light, the nystagmus (measured in darkness) decreased to 2.8 +/- 1.5 degrees /s (mean +/- SD) when recorded at the beginning but was 20.3 +/- 3.9 degrees /s at the end of the testing session. The latency of the VOR measured from responses to steps of acceleration (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) was 8.4 +/- 0.3 ms for responses to ipsilesional rotations and 7.7 +/- 0.4 ms for contralesional rotations. During the period that animals were kept in darkness after the labyrinthectomy, the gain of the VOR measured during the steps of acceleration was 0.67 +/- 0.12 for contralesional rotations and 0.39 +/- 0.04 for ipsilesional rotations. Within 18-24 h after return to light, the VOR gain for contralesional rotations increased to 0.87 +/- 0.08, whereas there was only a slight increase for ipsilesional rotations to 0.41 +/- 0. 06. A symmetrical increase in the gain measured at the plateau of head velocity was noted after the animals were returned to light. The VOR evoked by sinusoidal rotations of 2-15 Hz, +/-20 degrees /s, showed a better recovery of gain at lower (2-4 Hz) than at higher (6-15 Hz) frequencies. At 0.5 Hz, gain decreased symmetrically when the peak amplitude was increased from 20 to 100 degrees /s. At 10 Hz, gain was decreased for ipsilesional half-cycles and increased for contralesional half-cycles when velocity was raised from 20 to 50 degrees /s. A model incorporating Linear and nonLinear Pathways was used to simulate the data. Selective increases in the gain for the Linear Pathway accounted for the recovery in VOR gain for responses at the velocity plateau of the steps of acceleration and for the sinusoidal rotations at lower peak velocities. The increase in gain for contralesional responses to steps of acceleration and sinusoidal rotations at higher frequencies and velocities was due to an increase in the contribution of the nonLinear Pathway. This Pathway was driven into cutoff and therefore did not affect responses for rotations toward the lesioned side.
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horizontal vestibuloocular reflex evoked by high acceleration rotations in the squirrel monkey ii responses after canal plugging
Journal of Neurophysiology, 1999Co-Authors: David M Lasker, Douglas D. Backous, Anna Lysakowski, Griffin L Davis, Lloyd B MinorAbstract:The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral plugging of the three semicircular canals. During the period (1-4 days) that animals were kept in darkness after plugging, the gain during steps of acceleration (3, 000 degrees /s(2), peak velocity = 150 degrees /s) was 0.61 +/- 0.14 (mean +/- SD) for contralesional rotations and 0.33 +/- 0.03 for ipsilesional rotations. Within 18-24 h after animals were returned to light, the VOR gain for contralesional rotations increased to 0. 88 +/- 0.05, whereas there was only a slight increase in the gain for ipsilesional rotations to 0.37 +/- 0.07. A symmetrical increase in the gain measured at the plateau of head velocity was noted after animals were returned to light. The latency of the VOR was 8.2 +/- 0. 4 ms for ipsilesional and 7.1 +/- 0.3 ms for contralesional rotations. The VOR evoked by sinusoidal rotations of 0.5-15 Hz, +/-20 degrees /s had no significant half-cycle asymmetries. The recovery of gain for these responses after plugging was greater at lower than at higher frequencies. Responses to rotations at higher velocities for frequencies >/=4 Hz showed an increase in contralesional half-cycle gain, whereas ipsilesional half-cycle gain was unchanged. A residual response that appeared to be canal and not otolith mediated was noted after plugging of all six semicircular canals. This response increased with frequency to reach a gain of 0.23 +/- 0.03 at 15 Hz, resembling that predicted based on a reduction of the dominant time constant of the canal to 32 ms after plugging. A model incorporating Linear and nonLinear Pathways was used to simulate the data. The coefficients of this model were determined from data in animals with intact vestibular function. Selective increases in the gain for the Linear and nonLinear Pathways predicted the changes in recovery observed after canal plugging. An increase in gain of the Linear Pathway accounted for the recovery in VOR gain for both responses at the velocity plateau of the steps of acceleration and for the sinusoidal rotations at lower peak velocities. The increase in gain for contralesional responses to steps of acceleration and sinusoidal rotations at higher frequencies and velocities was due to an increase in the gain of the nonLinear Pathway. This Pathway was driven into inhibitory cutoff at low velocities and therefore made no contribution for rotations toward the ipsilesional side.
Timothy E Hullar - One of the best experts on this subject based on the ideXlab platform.
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horizontal vestibuloocular reflex evoked by high acceleration rotations in the squirrel monkey iii responses after labyrinthectomy
Journal of Neurophysiology, 2000Co-Authors: David M Lasker, Timothy E Hullar, Lloyd B MinorAbstract:The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral labyrinthectomy. Spontaneous nystagmus was measured at the beginning and end of each testing session. During the period that animals were kept in darkness (4 days), the nystagmus at each of these times measured approximately 20 degrees /s. Within 18-24 h after return to the light, the nystagmus (measured in darkness) decreased to 2.8 +/- 1.5 degrees /s (mean +/- SD) when recorded at the beginning but was 20.3 +/- 3.9 degrees /s at the end of the testing session. The latency of the VOR measured from responses to steps of acceleration (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) was 8.4 +/- 0.3 ms for responses to ipsilesional rotations and 7.7 +/- 0.4 ms for contralesional rotations. During the period that animals were kept in darkness after the labyrinthectomy, the gain of the VOR measured during the steps of acceleration was 0.67 +/- 0.12 for contralesional rotations and 0.39 +/- 0.04 for ipsilesional rotations. Within 18-24 h after return to light, the VOR gain for contralesional rotations increased to 0.87 +/- 0.08, whereas there was only a slight increase for ipsilesional rotations to 0.41 +/- 0. 06. A symmetrical increase in the gain measured at the plateau of head velocity was noted after the animals were returned to light. The VOR evoked by sinusoidal rotations of 2-15 Hz, +/-20 degrees /s, showed a better recovery of gain at lower (2-4 Hz) than at higher (6-15 Hz) frequencies. At 0.5 Hz, gain decreased symmetrically when the peak amplitude was increased from 20 to 100 degrees /s. At 10 Hz, gain was decreased for ipsilesional half-cycles and increased for contralesional half-cycles when velocity was raised from 20 to 50 degrees /s. A model incorporating Linear and nonLinear Pathways was used to simulate the data. Selective increases in the gain for the Linear Pathway accounted for the recovery in VOR gain for responses at the velocity plateau of the steps of acceleration and for the sinusoidal rotations at lower peak velocities. The increase in gain for contralesional responses to steps of acceleration and sinusoidal rotations at higher frequencies and velocities was due to an increase in the contribution of the nonLinear Pathway. This Pathway was driven into cutoff and therefore did not affect responses for rotations toward the lesioned side.
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Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. I. Normal responses.
Journal of neurophysiology, 1999Co-Authors: David M Lasker, Douglas D. Backous, Timothy E HullarAbstract:The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in five squirrel monkeys with intact vestibular function. The VOR evoked by steps of acceleration in darkness (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) began after a latency of 7.3 +/- 1.5 ms (mean +/- SD). Gain of the reflex during the acceleration was 14.2 +/- 5.2% greater than that measured once the plateau head velocity had been reached. A polynomial regression was used to analyze the trajectory of the responses to steps of acceleration. A better representation of the data was obtained from a polynomial that included a cubic term in contrast to an exclusively Linear fit. For sinusoidal rotations of 0.5-15 Hz with a peak velocity of 20 degrees /s, the VOR gain measured 0.83 +/- 0.06 and did not vary across frequencies or animals. The phase of these responses was close to compensatory except at 15 Hz where a lag of 5.0 +/- 0.9 degrees was noted. The VOR gain did not vary with head velocity at 0.5 Hz but increased with velocity for rotations at frequencies of >/=4 Hz (0. 85 +/- 0.04 at 4 Hz, 20 degrees /s; 1.01 +/- 0.05 at 100 degrees /s, P < 0.0001). No responses to these rotations were noted in two animals that had undergone bilateral labyrinthectomy indicating that inertia of the eye had a negligible effect for these stimuli. We developed a mathematical model of VOR dynamics to account for these findings. The inputs to the reflex come from Linear and nonLinear Pathways. The Linear Pathway is responsible for the constant gain across frequencies at peak head velocity of 20 degrees /s and also for the phase lag at higher frequencies being less than that expected based on the reflex delay. The frequency- and velocity-dependent nonLinearity in VOR gain is accounted for by the dynamics of the nonLinear Pathway. A transfer function that increases the gain of this Pathway with frequency and a term related to the third power of head velocity are used to represent the dynamics of this Pathway. This model accounts for the experimental findings and provides a method for interpreting responses to these stimuli after vestibular lesions.
Wadie F Bahou - One of the best experts on this subject based on the ideXlab platform.
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heme degradation enzyme biliverdin ixβ reductase is required for stem cell glutamine metabolism
Biochemical Journal, 2018Co-Authors: Natasha M Nesbitt, Lisa E Malone, Dimitri V Gnatenko, Daifeng Wang, Wei Zhu, Geoffrey D Girnun, Wadie F BahouAbstract:Bioenergetic requirements of hematopoietic stem cells and pluripotent stem cells (PSCs) vary with lineage fate, and cellular adaptations rely largely on substrate (glucose/glutamine) availability and mitochondrial function to balance tricarboxylic acid (TCA)-derived anabolic and redox-regulated antioxidant functions. Heme synthesis and degradation converge in a Linear Pathway that utilizes TCA cycle-derived carbon in cataplerotic reactions of tetrapyrrole biosynthesis, terminated by NAD(P)H-dependent biliverdin reductases (IXα, BLVRA and IXβ, BLVRB) that lead to bilirubin generation and cellular antioxidant functions. We now demonstrate that PSCs with targeted deletion of BLVRB display physiologically defective antioxidant activity and cellular viability, associated with a glutamine-restricted defect in TCA entry that was computationally predicted using gene/metabolite topological network analysis and subsequently validated by bioenergetic and isotopomeric studies. Defective BLVRB-regulated glutamine utilization was accompanied by exaggerated glycolytic accumulation of the rate-limiting hexokinase reaction product glucose-6-phosphate. BLVRB-deficient embryoid body formation (a critical size parameter of early lineage fate potential) demonstrated enhanced sensitivity to the pentose phosphate Pathway (PPP) inhibitor 6-aminonicotinamide with no differences in the glycolytic Pathway inhibitor 2-deoxyglucose. These collective data place heme catabolism in a crucial Pathway of glutamine-regulated bioenergetic metabolism and suggest that early stages of lineage fate potential require glutamine anaplerotic functions and an intact PPP, which are, in part, regulated by BLVRB activity. In principle, BLVRB inhibition represents an alternative strategy for modulating cellular glutamine utilization with consequences for cancer and hematopoietic metabolism.
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heme degradation enzyme biliverdin ixb reductase is required for stem cell glutamine metabolism
Blood, 2017Co-Authors: Wadie F BahouAbstract:Bioenergetic requirements of pluripotent stem cells (PSC) vary with lineage fate, and cellular adaptations rely largely on substrate availability and mitochondrial function to balance TCA-derived anabolic and redox-regulated antioxidant functions. Heme (protoporphyrin IX complexed with iron) serves as an indispensable co-factor for all aerobic cells, and its cytotoxicity is minimized by a two-step catabolic reaction that generates biliverdin (BV) and bilirubin (BR) tetrapyrroles, the penultimate step regulated by two non-redundant biliverdin reductases (IXa, BLVRA and IXb, BLVRB) retaining isomeric specificity and NAD(P)H-dependent redox coupling linked to BR antioxidant function. Thus, heme biosynthesis (initiated by the condensation of glycine and succinyl CoA) can be considered a Linear Pathway that utilizes cataplerotic TCA-derived carbon (derived from glucose and glutamine) linked to the heme degradation Pathway and bilirubin excretion. Given the overlapping glucose/glutamine requirements in both heme synthesis and PSC bioenergetics, we studied consequences of dysregulated heme metabolism by targeted BLVRB disruption in iPSCs derived from human umbilical cord CD34+ hematopoietic cells. Compared to control iPSCs, BLVRB-deficient iPSCs had no reciprocal BLVRA induction, no alterations in heme oxygenase expression, and no differences in isomeric BV accumulation, although phenotypically defective in antioxidant handling with exaggerated apoptotic cell death. To better delineate metabolic Pathway perturbations causally implicated in BLVRB- deficient antioxidant function and cell viability, we generated gene/metabolite clusters and an extended network plot formulated on RNASeq data coupled with liquid chromatography/mass spectrometric-based targeted metabolomics profiling of 290 intracellular metabolites. Metabolic enrichment with topological Pathway analysis identified a limited number of defective Pathways involving purine/pyrimidine nucleotide synthesis, redox homeostasis (pentose phosphate Pathway, PPP) and TCA cycle intermediates (a-ketoglutarate, fumarate, and malate). Mitochondrial staining using TMRE as a functional and quantifiable marker of the mitochondrial transmembrane potential (DYm) identified no defect across the genotypes, although BLVRB -deficient iPSCs demonstrated defective basal and maximal oxygen consumption rates (OCR) restricted to glutamine (but not glucose) utilization. Metabolic flux quantification using [U 6 - 13 C] glucose revealed high-level and comparable (>97%) fractional labeling of 13 C lactate across the genotypes, consistent with an active glycolytic metabolism that was comparable between control and BLVRB -/- iPSCs. In contrast, isotopic tracing using [U- 13 C 5 ] glutamine demonstrated statistically-diminished glutamate-derived aKG accumulation (along with downstream TCA metabolites fumarate and malate isotopomers), results confirming rewired glutamine TCA entry, and reliance on glucose as a preferred substrate. Since the parallel PPP Pathway utilizes glycolysis as the preferred substrate for generating both reducing equivalents (NADPH) and essential nucleotide component ribose-5-phosphate, we characterized three-dimensional embryoid body (EB) formation in the presence of the PPP Pathway inhibitor 6-aminonicotinamide (6-AN), establishing statistically-decreased EB size (p Disclosures No relevant conflicts of interest to declare.
Douglas D. Backous - One of the best experts on this subject based on the ideXlab platform.
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Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. I. Normal responses.
Journal of neurophysiology, 1999Co-Authors: David M Lasker, Douglas D. Backous, Timothy E HullarAbstract:The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in five squirrel monkeys with intact vestibular function. The VOR evoked by steps of acceleration in darkness (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) began after a latency of 7.3 +/- 1.5 ms (mean +/- SD). Gain of the reflex during the acceleration was 14.2 +/- 5.2% greater than that measured once the plateau head velocity had been reached. A polynomial regression was used to analyze the trajectory of the responses to steps of acceleration. A better representation of the data was obtained from a polynomial that included a cubic term in contrast to an exclusively Linear fit. For sinusoidal rotations of 0.5-15 Hz with a peak velocity of 20 degrees /s, the VOR gain measured 0.83 +/- 0.06 and did not vary across frequencies or animals. The phase of these responses was close to compensatory except at 15 Hz where a lag of 5.0 +/- 0.9 degrees was noted. The VOR gain did not vary with head velocity at 0.5 Hz but increased with velocity for rotations at frequencies of >/=4 Hz (0. 85 +/- 0.04 at 4 Hz, 20 degrees /s; 1.01 +/- 0.05 at 100 degrees /s, P < 0.0001). No responses to these rotations were noted in two animals that had undergone bilateral labyrinthectomy indicating that inertia of the eye had a negligible effect for these stimuli. We developed a mathematical model of VOR dynamics to account for these findings. The inputs to the reflex come from Linear and nonLinear Pathways. The Linear Pathway is responsible for the constant gain across frequencies at peak head velocity of 20 degrees /s and also for the phase lag at higher frequencies being less than that expected based on the reflex delay. The frequency- and velocity-dependent nonLinearity in VOR gain is accounted for by the dynamics of the nonLinear Pathway. A transfer function that increases the gain of this Pathway with frequency and a term related to the third power of head velocity are used to represent the dynamics of this Pathway. This model accounts for the experimental findings and provides a method for interpreting responses to these stimuli after vestibular lesions.
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horizontal vestibuloocular reflex evoked by high acceleration rotations in the squirrel monkey ii responses after canal plugging
Journal of Neurophysiology, 1999Co-Authors: David M Lasker, Douglas D. Backous, Anna Lysakowski, Griffin L Davis, Lloyd B MinorAbstract:The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral plugging of the three semicircular canals. During the period (1-4 days) that animals were kept in darkness after plugging, the gain during steps of acceleration (3, 000 degrees /s(2), peak velocity = 150 degrees /s) was 0.61 +/- 0.14 (mean +/- SD) for contralesional rotations and 0.33 +/- 0.03 for ipsilesional rotations. Within 18-24 h after animals were returned to light, the VOR gain for contralesional rotations increased to 0. 88 +/- 0.05, whereas there was only a slight increase in the gain for ipsilesional rotations to 0.37 +/- 0.07. A symmetrical increase in the gain measured at the plateau of head velocity was noted after animals were returned to light. The latency of the VOR was 8.2 +/- 0. 4 ms for ipsilesional and 7.1 +/- 0.3 ms for contralesional rotations. The VOR evoked by sinusoidal rotations of 0.5-15 Hz, +/-20 degrees /s had no significant half-cycle asymmetries. The recovery of gain for these responses after plugging was greater at lower than at higher frequencies. Responses to rotations at higher velocities for frequencies >/=4 Hz showed an increase in contralesional half-cycle gain, whereas ipsilesional half-cycle gain was unchanged. A residual response that appeared to be canal and not otolith mediated was noted after plugging of all six semicircular canals. This response increased with frequency to reach a gain of 0.23 +/- 0.03 at 15 Hz, resembling that predicted based on a reduction of the dominant time constant of the canal to 32 ms after plugging. A model incorporating Linear and nonLinear Pathways was used to simulate the data. The coefficients of this model were determined from data in animals with intact vestibular function. Selective increases in the gain for the Linear and nonLinear Pathways predicted the changes in recovery observed after canal plugging. An increase in gain of the Linear Pathway accounted for the recovery in VOR gain for both responses at the velocity plateau of the steps of acceleration and for the sinusoidal rotations at lower peak velocities. The increase in gain for contralesional responses to steps of acceleration and sinusoidal rotations at higher frequencies and velocities was due to an increase in the gain of the nonLinear Pathway. This Pathway was driven into inhibitory cutoff at low velocities and therefore made no contribution for rotations toward the ipsilesional side.