Ramifications of Gaba Receptor Subtypes on Retinal Information Processing

γ-Aminobutyric acid (GABA) receptors on retinal bipolar cells (BCs) are highly relevant to spatial and temporal integration of visual signals in the outer and inner retina. In the present work, subcellular localization and complements of GABAA and GABACreceptors on BCs were investigated by whole cell recordings and local drug application via multi-barreled puff pipettes in the bullfrog retinal slice preparation. Four types of the BCs (types 1–4) were identified morphologically by injection of Lucifer yellow. According to the ramification levels of the axon terminals and the responses of these cells to glutamate (or kainate) applied at their dendrites, types 1 and 2 of BCs were supposed to be off type, whereas types 3 and 4 of BCs might be on type. Bicuculline (BIC), a GABAA receptor antagonist, and imidazole-4-acetic acid (I4AA), a GABAC receptor antagonist, were used to distinguish GABA receptor-mediated responses. In all BCs tested, not only the axon terminals but also the dendrites showed high GABA sensitivity mediated by both GABAA and GABACreceptors. Subcellular localization and complements of GABAA and GABAC receptors at the dendrites and axon terminals were highly related to the dichotomy of offand on BCs. In the case of off BCs, GABAA receptors were rather evenly distributed at the dendrites and axon terminals, but GABAC receptors were predominantly expressed at the axon terminals. Moreover, the relative contribution of GABAC receptors to the axon terminals was prevalent over that of GABAA receptors, while the situation was reversed at the dendrites. In the case of on BCs, GABAA and GABAC receptors both preferred to be expressed at the axon terminals; relative contributions of these two GABA receptor subtypes to both the sites were comparable, while GABAC receptors were much less expressed than GABAA receptors. GABAA, but not GABAC receptors, were expressed clusteringly at axons of a population of BCs. In a minority of BCs, I4AA suppressed the GABAC responses at the dendrites, but not at the axon terminal, implying that the GABAC receptors at these two sites may be heterogeneous. Taken together, these results suggest that GABAA and GABAC receptors may play different roles in the outer and inner retina and the differential complements of the two receptors on off and on BCs may be closely related to physiological functions of these cells.

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Bipolar cell pathways for color vision in non-primate dichromats

Visual Neuroscience ◽

10.1017/s0952523810000271 ◽

2010 ◽

Vol 28 (1) ◽

pp. 51-60 ◽

Cited By ~ 26

Author(s):

CHRISTIAN PULLER ◽

SILKE HAVERKAMP

Keyword(s):

Color Vision ◽

Bipolar Cell ◽

Ganglion Cells ◽

Color Discrimination ◽

Model Systems ◽

Retinal Ganglion ◽

Retinal Pathways ◽

Retinal Information Processing ◽

Cone Opsins ◽

Retinal Information

AbstractColor vision in mammals is based on the expression of at least two cone opsins that are sensitive to different wavelengths of light. Furthermore, retinal pathways conveying color-opponent signals are required for color discrimination. Most of the primates are trichromats, and “color-coded channels” of their retinas are unveiled to a large extent. In contrast, knowledge of cone-selective pathways in nonprimate dichromats is only slowly emerging, although retinas of dichromats like mice or rats are extensively studied as model systems for retinal information processing. Here, we review recent progress of research on color-coded pathways in nonprimate dichromats to identify differences or similarities between di- and trichromatic mammals. In addition, we applied immunohistochemical methods and confocal microscopy to retinas of different species and present data on their neuronal properties, which are expected to contribute to color vision. Basic neuronal features such as the “blue cone bipolar cell” exist in every species investigated so far. Moreover, there is increasing evidence for chromatic OFF channels in dichromats and retinal ganglion cells that relay color-opponent signals to the brain. In conclusion, di- and trichromats share similar retinal pathways for color transmission and processing.

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Pathway-Specific Targeting of GABAA Receptor Subtypes to Somatic and Dendritic Synapses in the Central Amygdala

Journal of Neurophysiology ◽

10.1152/jn.2001.86.2.717 ◽

2001 ◽

Vol 86 (2) ◽

pp. 717-723 ◽

Cited By ~ 41

Author(s):

Andrew J. Delaney ◽

Pankaj Sah

Keyword(s):

Gaba Receptors ◽

Large Amplitude ◽

Gaba Receptor ◽

Small Amplitude ◽

Inhibitory Synapses ◽

Receptor Subtypes ◽

Central Amygdala ◽

Low Concentrations ◽

Gabaa Receptor Subtypes ◽

Minimal Stimulation

Neurons in the central amygdala express two distinct types of ionotropic GABA receptor. One is the classical GABAA receptor that is blocked by low concentrations of bicuculline and positively modulated by benzodiazepines. The other is a novel type of ionotropic GABA receptor that is less sensitive to bicuculline but blocked by the GABAC receptor antagonist (1,2,5,6-tetrohydropyridine-4-yl) methylphosphinic acid (TPMPA) and by benzodiazepines. In this study, we examine the distribution of these two receptor types. Recordings of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) showed a wide variation in amplitude. Most events had amplitudes of <50 pA, but a small minority had amplitudes >100 pA. Large-amplitude events also had rise times faster than small-amplitude events. Large-amplitude events were fully blocked by 10 μM bicuculline but unaffected by TPMPA. Small amplitude events were partially blocked by both bicuculline and TPMPA. Focal application of hypertonic sucrose to the soma evoked large-amplitude mIPSCs, whereas focal dendritic application of sucrose evoked small-amplitude mIPSCs. Thus inhibitory synapses on the dendrites of neurons in the central amygdala express both types of GABA receptor, but somatic synapses expressed purely GABAA receptors. Minimal stimulation revealed that inhibitory inputs arising from the laterally located intercalated cells innervate dendritic synapses, whereas inhibitory inputs of medial origin innervated somatic inhibitory synapses. These results show that different types of ionotropic GABA receptors are targeted to spatially and functionally distinct synapses. Thus benzodiazepines will have different modulatory effects on different inhibitory pathways in the central amygdala.

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Homomeric RDL and Heteromeric RDL/LCCH3 GABA Receptors in the Honeybee Antennal Lobes: Two Candidates for Inhibitory Transmission in Olfactory Processing

Journal of Neurophysiology ◽

10.1152/jn.00798.2009 ◽

2010 ◽

Vol 103 (1) ◽

pp. 458-468 ◽

Cited By ~ 31

Author(s):

Julien Pierre Dupuis ◽

Michaël Bazelot ◽

Guillaume Stéphane Barbara ◽

Sandrine Paute ◽

Monique Gauthier ◽

...

Keyword(s):

Information Processing ◽

Chloride Channel ◽

Gaba Receptors ◽

Gaba Receptor ◽

Chloride Channels ◽

Physiological Role ◽

Inhibitory Transmission ◽

Olfactory Information ◽

Whole Cell Patch Clamp ◽

Inward Currents

γ-Aminobutyric acid (GABA)–gated chloride channel receptors are abundant in the CNS, where their physiological role is to mediate fast inhibitory neurotransmission. In insects, this inhibitory transmission plays a crucial role in olfactory information processing. In an effort to understand the nature and properties of the ionotropic receptors involved in these processes in the honeybee Apis mellifera, we performed a pharmacological and molecular characterization of GABA-gated channels in the primary olfactory neuropile of the honeybee brain—the antennal lobe (AL)—using whole cell patch-clamp recordings coupled with single-cell RT-PCR. Application of GABA onto AL cells at −110 mV elicited fast inward currents, demonstrating the existence of ionotropic GABA-gated chloride channels. Molecular analysis of the GABA-responding cells revealed that both subunits RDL and LCCH3 were expressed out of the three orthologs of Drosophila melanogaster GABA-receptor subunits encoded within the honeybee genome (RDL, resistant to dieldrin; GRD, GABA/glycine-like receptor of Drosophila ; LCCH3, ligand-gated chloride channel homologue 3), opening the door to possible homo- and/or heteromeric associations. The resulting receptors were activated by insect GABA-receptor agonists muscimol and CACA and blocked by antagonists fipronil, dieldrin, and picrotoxin, but not bicuculline, displaying a typical RDL-like pharmacology. Interestingly, increasing the intracellular calcium concentration potentiated GABA-elicited currents, suggesting a modulating effect of calcium on GABA receptors possibly through phosphorylation processes that remain to be determined. These results indicate that adult honeybee AL cells express typical RDL-like GABA receptors whose properties support a major role in synaptic inhibitory transmission during olfactory information processing.

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Recent progress on the role of GABAergic neurotransmission in the pathogenesis of Alzheimer’s disease

Reviews in the Neurosciences ◽

10.1515/revneuro-2015-0062 ◽

2016 ◽

Vol 27 (4) ◽

pp. 449-455 ◽

Cited By ~ 3

Author(s):

Ghulam Abbas ◽

Wajahat Mahmood ◽

Nurul Kabir

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gaba Receptor ◽

Amyloid Β ◽

Receptor Subtypes ◽

Causative Role ◽

Gabaergic Neurotransmission ◽

Promising Target ◽

The Brain

AbstractDespite their possible causative role, targeting amyloidosis, tau phosphorylation, acetylcholine esterase, glutamate, oxidative stress and mitochondrial metabolism have not yet led to the development of drugs to cure Alzheimer’s disease (AD). Recent preclinical and clinical reports exhibit a surge in interest in the role of GABAergic neurotransmission in the pathogenesis of AD. The interaction among GABAergic signaling, amyloid-β and acetylcholine is shown to affect the homeostasis between excitation (glutamate) and inhibition (GABA) in the brain. As a consequence, over-excitation leads to neurodegeneration (excitotoxicity) and impairment in the higher level functions. Previously, the glutamate arm of this balance received the most attention. Recent literature suggests that over-excitation is primarily mediated by dysfunctional GABA signaling and can possibly be restored by rectifying anomalous metabolism observed in the GABAergic neurons during AD. Additionally, neurogenesis and synaptogenesis have also been linked with GABAergic signaling. This association may provide a basis for the needed repair mechanism. Furthermore, several preclinical interventional studies revealed that targeting various GABA receptor subtypes holds potential in overcoming the memory deficits associated with AD. In conclusion, the recent scientific literature suggests that GABAergic signaling presents itself as a promising target for anti-AD drug development.

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