VISUO-VESTIBULAR REFLEXES ADJUSTMENT BY GABA ANTAGONISTS

AbstractGABA is a major inhibitory neurotransmitter in the mammalian retina and it acts at many different sites via a variety of postsynaptic receptors. These include GABAA receptors and bicuculline-resistant GABAC receptors. The release of acetylcholine (ACh) is inhibited by GABA and strongly potentiated by GABA antagonists. In addition, GABA appears to mediate the null inhibition which is responsible for the mechanism of directional selectivity in certain ganglion cells. We have used these two well-known examples of GABA inhibition to compare three GABA antagonists and assess the contributions of GABAA and GABAC receptors. All three GABA antagonists stimulated ACh release by as much as ten-fold. By this measure, the ED50s for SR-95531, bicuculline, and picrotoxin were 0.8, 7.0, and 14 μM, respectively. Muscimol, a potent GABAA agonist, blocked the effects of SR-95531 and bicuculline, but not picrotoxin. This indicates that SR-95531 and bicuculline are competitive antagonists at the GABAA receptor, while picrotoxin blocks GABAA responses by acting at a different, nonreceptor site such as the chloride channel. In the presence of a saturating dose of SR-95531 to completely block GABAA receptors, picrotoxin caused a further increase in the release of ACh. This indicates that picrotoxin potentiates ACh release by a mechanism in addition to the block of GABAA responses, possibly by also blocking GABAC receptors, which have been associated with bipolar cells. All three GABA antagonists abolished directionally selective responses from ON/OFF directional-selective (DS) ganglion cells. In this system, the ED50s for SR-95531, bicuculline, and picrotoxin were 0.7 μM, 8 μM, and 94.6 μM, respectively. The results with SR-95531 and bicuculline indicate that GABAA receptors mediate the inhibition responsible for directional selectivity. The addition of picrotoxin to a high dose of SR-95531 caused no further increase in firing rate. The comparatively high dose required for picrotoxin also suggests that GABAC receptors do not contribute to directional selectivity. This in turn suggests that feedforward GABAA inhibition, as opposed to feedback at bipolar terminals, is responsible for the null inhibition underlying directional selectivity.

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Anodal vestibular stimulation does not suppress vestibular reflexes in human subjects

Experimental Brain Research ◽

10.1007/s00221-003-1489-2 ◽

2003 ◽

Vol 150 (4) ◽

pp. 525-528 ◽

Cited By ~ 3

Author(s):

Ann M. Bacsi ◽

James G. Colebatch

Keyword(s):

Human Subjects ◽

Vestibular Stimulation ◽

Vestibular Reflexes

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Dynamics of neck-to-forelimb reflexes in the decerebrate cat

Journal of Neurophysiology ◽

10.1152/jn.1983.50.3.688 ◽

1983 ◽

Vol 50 (3) ◽

pp. 688-695 ◽

Cited By ~ 25

Author(s):

K. Ezure ◽

V. J. Wilson

Keyword(s):

Head Rotation ◽

Longitudinal Axis ◽

Triceps Brachii ◽

Vestibular Reflexes ◽

Sinusoidal Analysis ◽

Low Frequencies ◽

Decerebrate Cat ◽

Splenius Capitis ◽

Response Phase ◽

Stimulation Of

We have studied the neck-to-forelimb reflex evoked by head rotation around the longitudinal axis (roll) in the long and medial heads of triceps brachii of decerebrate, acutely labyrinthectomized cats. Reflexes were measured by recording mass electromyogram (EMG). As expected from the work of others, they were reciprocal in the two limbs, with excitation in the limb toward which the chin rotates. The reflex was sufficiently linear for a sinusoidal analysis. Although there was sometimes adaptation at stimulus frequencies of 0.1 Hz and below, response phase at these frequencies was usually in phase with position, and gain was flat. At higher frequencies there was some sensitivity to the velocity of the stimulus: gain increased with a slope of 10 dB/decade and phase advanced in some cats but not in others. Gain at low frequencies of head rotation, expressed as percent modulation of EMG, was typically 1%/deg or less. Reflexes evoked by head rotation in triceps and in the neck extensor splenius capitis have different dynamics. It remains to be determined whether this difference is due to activation of different receptors. We compared the dynamics of roll reflexes evoked by stimulation of neck receptors with those of vestibular reflexes evoked by tilt of the whole animal (23). Taking into account dynamics and gain, the two reflexes should cancel at low frequencies, as predicted by others. Above 0.2 Hz, cancellation becomes less effective.

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Extracting phase-dependent human vestibular reflexes during locomotion using both time and frequency correlation approaches

Journal of Applied Physiology ◽

10.1152/japplphysiol.00621.2011 ◽

2011 ◽

Vol 111 (5) ◽

pp. 1484-1490 ◽

Cited By ~ 25

Author(s):

Jean-Sébastien Blouin ◽

Christopher J. Dakin ◽

Kees van den Doel ◽

Romeo Chua ◽

Bradford J. McFadyen ◽

...

Keyword(s):

Vestibular Stimulation ◽

Time Dependent ◽

Medial Gastrocnemius ◽

Electromyographic Activity ◽

Step Cycle ◽

Vestibular Reflexes ◽

Time Frequency ◽

Dynamic Modulation ◽

Frequency Decomposition ◽

Heel Contact

Daily activities, such as walking, may require dynamic modulation of vestibular input onto motoneurons. This dynamic modulation is difficult to identify in humans due to limitations in the delivery and analysis of current vestibular probes, such as galvanic vestibular stimulation. Stochastic vestibular stimulation, however, provides an alternative method to extract human vestibular reflexes. Here, we used time-dependent coherence and time-dependent cross-correlation, coupled with stochastic vestibular stimulation, to investigate the phase dependency of human vestibular reflexes during locomotion. We found that phase-dependent activity from the medial gastrocnemius muscles is correlated with the vestibular signals over the 2- to 20-Hz bandwidth during the stance phase of locomotion. Vestibular-gastrocnemius coherence and time-dependent cross-correlations reached maximums at 21 ± 4 and 23 ± 8% of the step cycle following heel contact and before the period of maximal electromyographic activity (38 ± 5%). These results demonstrate 1) the effectiveness of these techniques in extracting the phase-dependent modulation of vestibulomuscular coupling during a cyclic task; 2) that vestibulomuscular coupling is phasically modulated during locomotion; and 3) that the period of strongest vestibulomuscular coupling does not correspond to the period of maximal electromyographic activity in the gastrocnemius. Therefore, we have shown that stochastic vestibular stimulation, coupled with time-frequency decomposition, provides an effective tool to assess the contribution of vestibular ex-afference to the muscular control during locomotion.

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Role of GABAergic Inhibition in the Coding of Interaural Time Differences of Low-Frequency Sounds in the Inferior Colliculus

Journal of Neurophysiology ◽

10.1152/jn.00956.2004 ◽

2005 ◽

Vol 93 (6) ◽

pp. 3390-3400 ◽

Cited By ~ 17

Author(s):

W. R. D’Angelo ◽

S. J. Sterbing ◽

E.-M. Ostapoff ◽

S. Kuwada

Keyword(s):

Inferior Colliculus ◽

Signal To Noise Ratio ◽

Interaural Time Difference ◽

Low Frequency ◽

Gabaergic Inhibition ◽

Interaural Time Differences ◽

Gaba Antagonists ◽

Inhibitory Transmitter ◽

Almost All

A major cue for the localization of sound in space is the interaural time difference (ITD). We examined the role of inhibition in the shaping of ITD responses in the inferior colliculus (IC) by iontophoretically ejecting γ-aminobutyric acid (GABA) antagonists and GABA itself using a multibarrel pipette. The GABA antagonists block inhibition, whereas the applied GABA provides a constant level of inhibition. The effects on ITD responses were evaluated before, during and after the application of the drugs. If GABA-mediated inhibition is involved in shaping ITD tuning in IC neurons, then applying additional amounts of this inhibitory transmitter should alter ITD tuning. Indeed, for almost all neurons tested, applying GABA reduced the firing rate and consequently sharpened ITD tuning. Conversely, blocking GABA-mediated inhibition increased the activity of IC neurons, often reduced the signal-to-noise ratio and often broadened ITD tuning. Blocking GABA could also alter the shape of the ITD function and shift its peak suggesting that the role of inhibition is multifaceted. These effects indicate that GABAergic inhibition at the level of the IC is important for ITD coding.

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