The role of GABA-mediated inhibition in the rat ventral posterior medial thalamus. II. Differential effects of GABAA and GABAB receptor antagonists on responses of VPM neurons.
1. Changes in the response properties of 106 ventral posterior medial (VPM) units were assessed after iontophoretic blockade of gamma-aminobutyric acid-A or -B (GABAA or GABAB) receptor-mediated inhibition using bicuculline methiodide (BIC) or 2-hydroxy-saclofen (2-OH-S), respectively. 2. The iontophoretic administration of either BIC or 2-OH-S did not alter significantly the average spontaneous firing rate of VPM neurons for current intensities between 40 and 80 nA. The presence of 10 mM 2-OH-S (60 nA) was effective in completely reversing the depressant effects of the selective GABAB receptor agonist, baclofen, on the spontaneous activity of VPM neurons. 3. The effect of BIC on whisker-evoked responses was a preferential enhancement in the responses elicited by the whisker giving rise to the highest probability response (center receptive field whisker or CRF). The effect of 2-OH-S (40-80 nA iontophoretic currents) was to increase the responsiveness of VPM neurons to the stimulation of whiskers in all parts of the receptive field (RF), although its influence was much more pronounced in the peripheral areas of the RF (surround receptive field whisker or SRF). This preferential enhancement of SRF-whisker responses after the blockade of GABAB receptor-mediated inhibition resulted in a 2.3-fold increase in the average RF size of VPM neurons; no statistically significant increases in the size of the RF were seen in the presence of BIC. 4. The primary influence of BIC and, to a lesser degree, 2-OH-S was to prolong the response duration of VPM neurons to CRF whisker stimulation. Under our recording conditions, approximately 25% of VPM neurons in normal animals responded with sustained discharges. In the presence of BIC and 2-OH-S, the percent of VPM units that could be classified as tonically responding increased to 82% and 67%, respectively. 5. The proportion of VPM neurons that was selective to the deflection of whiskers in a particular direction (87%) was not altered in the presence of BIC or 2-OH-S. 6. BIC was effective in antagonizing GABA-mediated inhibition within the first 40 ms of a stimulus; BIC was completely ineffective in reversing a late suppression seen between 80 and 140 ms. In contrast, no statistically significant changes in the initial GABA-mediated inhibition were seen in the presence of 2-OH-S, but 2-OH-S was partially effective in antagonizing the late suppression of responses in VPM neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
Lee
S M
SM
Institute for Developmental Neuroscience, Vanderbilt University, Nashville, Tennessee 37203.
Friedberg
M H
MH
Ebner
F F
FF
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D001931:Brain Mapping; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects / Q000502:physiology; D005260:Female; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013787:Thalamic Nuclei / Q000187:drug effects / Q000502:physiology*; D014738:Vibrissae / Q000294:innervation; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; C057491:2-hydroxysaclofen; D001640:Bicuculline