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Effects of Whisker-Trimming on GABAA Receptors in S1 CortexSalazar, Eduardo 08 1900 (has links)
A number of studies have shown that sensory deprivation is associated with selective decreases in GABA, GAD, and GABA receptors, in deprived areas of visual and somatosensory cortex. Those studies focused on layer 4, a recipient of direct thalamocortical sensory input. However, supragranular layers 2/3 have been recently identified as a major locus of functional plasticity in sensory deprivation and long-term potentiation. To examine whether GABAA receptors in layers 2/3 are affected by sensory deprivation, rats had mystacial vibrissae in middle row C or rows ABDE trimmed for 6 weeks beginning in early adulthood. Layers 2/3 above the deprived and adjacent whisker barrels were located in tangential sections, using patterns of radial blood vessels as fiducial marks. In deprived whisker barrel columns, [3H]muscimol binding to GABAA receptors decreased by 12.8% ± 1.2 (P < 0.001) in layers 2/3 and 11.4% ± 1.2 (P<0.001) in layer 4. Altered levels of GABAA α1 subunit (Fritschy et al., 1994) were indicated by reduced optical density of immunostaining, both in deprived layers 2/3 (6.4% ± 0.7; P< 0.001) and in layer 4 (3.4% ± 1.0; P < 0.005). Interestingly, Nissl staining density also decreased in deprived layers 2/3 (12.7% ± 1.8 P < 0.001) and in 4 (6.0 ± 0.7 (P < 0.001). The percent decreases were greater in layers 2/3 than in 4 for both GABAA α1 (P < 0.05) and Nissl substance (P < 0.005). The present results suggest that down-regulation in GABAA receptors may underlie the physiological signs of disinhibition observed in neurons of layer 2/3 and 4 in deprived whisker barrel columns.
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GABAa receptor pharmacology : electrophysiological studies of agonist activity on reconstituted human GABAa receptors /Mortensen, Martin. January 2002 (has links)
Ph.d.
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Conformational changes in the GABAA receptor during channel gating and alcohol modulationJung, Sangwook 28 August 2008 (has links)
Not available / text
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Ionotropic GABA receptor ligands and transport drugs : synthesis and characterization /Seir Petersen, Dorte Krehan. January 2002 (has links)
Ph.d.
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GABAergic transmission in developmental establishment of a gravity-related spatial referenceCao, Zhiwen., 曹志文. January 2011 (has links)
In rats, the subnuclei of the inferior olive (IO) and thalamus exist
topographic spatial representation to sinusoidal horizontal linear translations along either the antero-posterior or interaural direction. To examine the effect of GABAergic neurotransmission within the vestibular nucleus on the establishment of gravity-related topographic spatial representation in relay station of the central vestibular pathway, GABAA receptor antagonist bicuculline was used to chronically perturb GABA transmission within the vestibular nucleus of postnatal rats. Implantation of bicuculline-loaded or saline-loaded Elvax slice onto the dorsal surface of vestibular nucleus was performed in P1 rats which were allowed to recover into adulthood. Fos protein expression was used as an indicator to identify central neurons responsive to horizontal linear accelerations. In stationary or labyrinthectomized rats, Fos-immunoreactive (ir) neurons were either absent or sporadically scattered throughout the IO and thalamic subnuclei, indicating that the Fos expression in these neural area was otolithic in origin. In the saline control group, Fos expression induced by horizontal antero-posterior linear acceleration was observed in both the IO and thalamus. Responsive IO subnuclei include β subnucleus of IO and dorsomedial cell column while those in the thalamus include central medial nucleus, paracentral nucleus, mediodorsal nucleus, central lateral nucleus, zona incerta and subparafascicular nucleus of thalamus. For-ir neurons responsive to horizontal interaural linear acceleration were found in those IO subnuclei and thalamic subnuclei. When compared with the saline-treated group, the number of Fos-ir IO neurons responsive to horizontal linear acceleration was significantly lower in adult rats perturbed with bicuculline at P1. Besides, the pattern of Fos expression in both the IO and thalamus was altered in adult rats pretreated with bicuculline. In the utricle-related thalamic subnuclei, the postnatal time when Fos-ir neurons were found triggered by otolithic stimulation was delayed and the number of these Fos-ir neurons was fewer in the bicuculline-treated group than those in the saline-treated group. To investigate whether there exists a critical period for postnatal establishment of topographic spatial representation in the IO and thalamus, implantation of bicuculline-loaded Elvax slice onto the vestibular nucleus was carried out in P14 rats. The topographic spatial representation in IO and thalamus of those rats were unchanged as compared with adult rats pretreated with saline at P14. These results indicate that the GABAergic neuronal circuit in the vestibular nucleus plays an important role in postnatal establishment of topographic spatial representation in the central vestibular system. Most importantly, we documented the occurrence of a postnatal critical period (between P1 and P14) during which GABAergic transmission
regulated the formation of a gravity-related spatial framework in the brain. / published_or_final_version / Physiology / Master / Master of Philosophy
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Maturation profile of GABA-ergic inhibition in the vestibular nucleus : role in developmental plasticity and spatial recognitionHu, Huijing, 扈慧静 January 2011 (has links)
Inhibitory synaptic transmission within the vestibular circuits plays an essential
regulatory role in coordinating vestibular functions. The maturation profile of γ-
aminobutyric acid (GABA) synapses in the vestibular system remains unknown. To
address this, we first used double immunohistochemistry to document the postnatal
expression profile of GABAA receptors in canal-related and saccule-related vestibular
nuclear neurons of rats. The proportion of Fos / GABAA receptors α1 subunit doublelabeled
neurons progressively increased with age. Whole-cell patch-clamp experiments
on brainstem slice preparations were also employed to characterize the developmental
properties of these synapses within the medial vestibular nucleus. The frequency of
GABAA receptor-mediated miniature inhibitory postsynaptic currents (IPSC)
progressively increased during the first two postnatal weeks and reached a plateau
thereafter. This is in agreement with an increase in sensitivity to GABAA receptor α1
subunit agonist zolpidem during the same period. The rise time and decay time however
decreased by 2-fold. These results suggest that change in the composition of GABAA
receptor occurs during the functional maturation of medial vestibular neurons.
To further investigate whether GABA receptors contribute to synaptic plasticity in
the developing vestibular nucleus, two stimulus protocols were used. Repetitive
depolarizing pulses induced long-lasting decrease in the frequency of GABAA receptormediated
spontaneous IPSCs between P3 and P7. The probability of inducing such
frequency decline of sIPSCs decreased after the first postnatal week. High frequency
stimulation on the other hand, induced long-term depression (LTD) of GABAA receptormediated
evoked IPSCs between P3 and P5. The probability of inducing LTD decreased
after P14. These results indicate that LTD at GABAergic synapses could be easily
induced in developing medial vestibular neurons before maturation of GABAergic
synaptic transmission.
To examine if GABAergic transmission within the vestibular nucleus is crucial
for establishment of gravity-related spatial organization, an intervention approach was
adopted to perturb GABAergic transmission within the postnatal vestibular nucleus. A
slice of Elvax loaded with either GABAA receptor agonist muscimol or antagonist
bicuculline was inserted into the fourth ventricle and covered the bilateral vestibular
nuclei at different ages. Expression of Fos protein in functionally activated neurons was
used to demarcate the topographic spatial map in the inferior olive. The spatial map in
subnuclei IOβ and DMCC was disturbed in each adult rat that was implanted with
bicuculline- or muscimol-loaded Elvax at P1. However, no change was observed in
adult rats that were pretreated with bicuculline or muscimol at P14 or P21. Vestibularrelated
behavior tests were also performed. The acquisition of negative geotaxis, an
otolith-related orientation reflex, was delayed in postnatal rats pretreated with bicuculline
but was advanced in those rats pretreated with muscimol. Furthermore, the acquisition of
motor learning, evaluated by rotarod test, was impaired in adult rats treated with
bicuculline or muscimol.
Taken together, our results indicated that maturation of GABAergic transmission
within the vestibular nucleus play important roles in development of spatial recognition
and vestibular-related behavior. / published_or_final_version / Physiology / Doctoral / Doctor of Philosophy
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Synthesis of 4-alkyl-3,5-diamino-1-phenylpyrazolesDunham, Jason C. January 2006 (has links)
The goal of this project is to synthesize and purify a library of novel 4-alkyl-3,5-diamino-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazoles. These molecules are similar to other fiproles, which have been shown by Sammelson et al. to have pesticidal activities at the GABA receptor.' Fiproles are analogues of Fipronil, a very important pesticide. Replacing the cyano group normally located at the 3-position of the pyrazole ring with an amino group will change the binding potency of the phenylpyrazoles. Changes in binding produced by the changes introduced in molecular structure can create more information about the GABA receptor.Synthesis of our target compounds starts with production of monosubstituted malononitriles. Conventionally a two-step process, our research developed a new, efficient one-step process using borohydride as the only reagent. We utilized this method in the synthesis of desired monosubstituted malononitriles. These were converted to unsymmetrical disubstituted malononitriles, and to our target fiprole compounds, through a 4-alkyl-3,5-diaminopyrazole intermediate. / Department of Chemistry
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The GABAa Receptor in the Central Nervous System of a Rat Model of EpilepsySherman, John Mark 08 1900 (has links)
This study investigated the β-subunit of the GABAa receptor and determine if there are changes in the primary sequence of the extracellular N-Terminal domain, which likely regulates GABA binding.
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The Role of Gabergic Inhibition in Modulating Receptive Field Size of Cuneate NeuronsTennison, Cullen F. 08 1900 (has links)
A blockade of GABAergic inhibition increases the receptive field(RF) size of most
somatosensory cortex (SI) and some ventrobasal thalamus (VB) neurons. The results suggest RF size of cuneate neurons may be modulated through GABAa and
GABAb receptors, independent of firing frequency.
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Mutation of sites in alpha subunits alters pharmacology and function of glycine and GABA[subscript A] receptorsFindlay, Geoffrey Steven, 1975- 29 June 2011 (has links)
Not available / text
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