GABAergic

About: GABAergic is a research topic. Over the lifetime, 9595 publications have been published within this topic receiving 473568 citations.

GABAergic Neurons and Their Role in Cortical Plasticity in Primates

Abstract: GABA neurons and GABA receptors are conspicuous elements of cerebral cortical organization. They serve to shape the stimulus-response properties of neurons in the sensory areas and undoubtedly play a comparable role in the nonsensory areas as well. Although non-GABAergic local circuit neurons exist in the cerebral cortex, the variety of forms adopted by the GABAergic neurons and their important functional role have served to focus attention on the latter in investigations of local cortical circuitry. In primate neocortex, GABAergic neurons constitute approximately 25-30% of the neuronal population. In addition to their known or postulated functions in shaping neuronal receptive fields and response profiles, some of which are still controversial (Sillito, 1984; Ferster, 1986), their transmitter, GABA, and the major class of receptor upon which it acts are regulated in an activity-dependent manner even in the adult (Jones, 1990). In this, there is a potential mechanism for the plasticity of representational maps that is demonstrable in somatic sensory, motor, auditory, and visual cortex (Merzenich et al., 1983; Sanes et al., 1988; Robertson and Irvine, 1989; Kaas et al., 1990).

Three distinct families of GABAergic neurons in rat visual cortex.

Abstract: In the cortex inhibition is mediated predominantly by GABAergic interneurons. Although all of these neurons use the same neurotransmitter, studies in the rat frontal cortex have shown that they are molecularly and physiologically diverse. It is not known whether similar subgroups of GABAergic neurons exist in primary visual cortex and how these different inhibitory neurons are inserted into specific cortical circuits. We have used immunostaining with antibodies against gamma aminobutyric acid (GABA), parvalbumin (PV), calretinin (CR), somatostatin (SOM), calbindin (CB) and nitric oxide synthase (NOS) to probe for colocalization of known markers of GABAergic interneurons. The results show that the majority of PV (100%), SOM (89.8%) and CR (93.9%) staining neurons are GABA positive. PV immunoreactive neurons constitute a distinct group that show no overlap with CR, SOM and NOS expressing cells and only a minor overlap (5.3%) with CB. PV immunoreactive cells account for 50.8% of GABAergic neurons. A second group of SOM expressing neurons accounts for 16.9% of GABAergic cells. None of these cells colocalize PV or CR, but 1.7% of SOM neurons stain for NOS and 86.3% show CB immunoreactivity. The third distinct group of CR expressing cells accounts for 17.0% of GABAergic neurons. All of these are PV, CB, SOM and NOS negative. CB expressing neurons represent a heterogeneous group that includes GABAergic and non-GABAergic cells. Our findings indicate that GABAergic neurons in rat area 17 are organized in at least three separate families that can be identified by the expression of PV, CR and SOM. These cells account for 84.9% of GABAergic neurons. These results extend previous observations in rat frontal agranular cortex and suggest that in visual cortex the inhibitory network is composed of similar cell types.

Estradiol Increases Dendritic Spine Density by Reducing GABA Neurotransmission in Hippocampal Neurons

Abstract: We have previously shown that estradiol causes a twofold rise in dendritic spine density in cultured rat hippocampal neurons, as it doesin vivo. More recently, estrogen receptors have been localized to aspiny inhibitory hippocampal interneurons, indicating that their effect on spiny pyramidal neurons may be indirect. We therefore examined the possibility that estradiol affects spine density by regulating inhibition in cultured hippocampal interneurons. Immunocytochemically, estrogen receptors were found to be co-localized with glutamate decarboxylase (GAD)-positive neurons (∼21% of total neurons in the culture). Exposure of cultures to estradiol for 1 d caused a marked decrease (up to 80%) in the GAD content of the interneurons, measured both by immunohistochemistry and Western blotting. Also, the number of GAD-positive neurons in the cultures decreased to 12% of the total cell population. Moreover, GABAergic miniature IPSCs were reduced in both size and frequency by estradiol, whereas miniature EPSCs increased in frequency. We then mimicked the proposed effects of estradiol by blocking GABA synthesis with mercaptopropionic acid (MA). Cultures treated with MA expressed a dose-dependent decrease in GABA immunostaining that mimicked that seen with estradiol. MA-treated cultures displayed a significant 50% increase in dendritic spine density over controls, similar to that produced by estradiol. These results indicate that estradiol decreases GABAergic inhibition in the hippocampus, which appears to effectively increase the excitatory drive on pyramidal cells, and thus may provide a mechanism for formation of new dendritic spines.

Role of GABAergic Inhibition in Shaping Odor-Evoked Spatiotemporal Patterns in the Drosophila Antennal Lobe

Abstract: Drosophila olfactory receptor neurons project to the antennal lobe, the insect analog of the mammalian olfactory bulb GABAergic synaptic inhibition is thought to play a critical role in olfactory processing in the antennal lobe and olfactory bulb However, the properties of GABAergic neurons and the cellular effects of GABA have not been described in Drosophila, an important model organism for olfaction research We have used whole-cell patch-clamp recording, pharmacology, immunohistochemistry, and genetic markers to investigate how GABAergic inhibition affects olfactory processing in the Drosophila antennal lobe We show that many axonless local neurons (LNs) in the adult antennal lobe are GABAergic GABA hyperpolarizes antennal lobe projection neurons (PNs) via two distinct conductances, blocked by a GABAA- and GABAB-type antagonist, respectively Whereas GABAA receptors shape PN odor responses during the early phase of odor responses, GABAB receptors mediate odor-evoked inhibition on longer time scales The patterns of odor-evoked GABAB-mediated inhibition differ across glomeruli and across odors Finally, we show that LNs display broad but diverse morphologies and odor preferences, suggesting a cellular basis for odor- and glomerulus-dependent patterns of inhibition Together, these results are consistent with a model in which odors elicit stimulus-specific spatial patterns of GABA release, and as a result, GABAergic inhibition increases the degree of difference between the neural representations of different odors

Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies

Abstract: Summary Background Increasing evidence suggests that seizures and status epilepticus can be immune-mediated. We aimed to describe the clinical features of a new epileptic disorder, and to establish the target antigen and the effects of patients' antibodies on neuronal cultures. Methods In this observational study, we selected serum and CSF samples for antigen characterisation from 140 patients with encephalitis, seizures or status epilepticus, and antibodies to unknown neuropil antigens. The samples were obtained from worldwide referrals of patients with disorders suspected to be autoimmune between April 28, 2006, and April 25, 2013. We used samples from 75 healthy individuals and 416 patients with a range of neurological diseases as controls. We assessed the samples using immunoprecipitation, mass spectrometry, cell-based assay, and analysis of antibody effects in cultured rat hippocampal neurons with confocal microscopy. Findings Neuronal cell-membrane immunoprecipitation with serum of two index patients revealed GABA A receptor sequences. Cell-based assay with HEK293 expressing α1/β3 subunits of the GABA A receptor showed high titre serum antibodies (>1:160) and CSF antibodies in six patients. All six patients (age 3–63 years, median 22 years; five male patients) developed refractory status epilepticus or epilepsia partialis continua along with extensive cortical-subcortical MRI abnormalities; four patients needed pharmacologically induced coma. 12 of 416 control patients with other diseases, but none of the healthy controls, had low-titre GABA A receptor antibodies detectable in only serum samples, five of them also had GAD-65 antibodies. These 12 patients (age 2–74 years, median 26·5 years; seven male patients) developed a broader spectrum of symptoms probably indicative of coexisting autoimmune disorders: six had encephalitis with seizures (one with status epilepticus needing pharmacologically induced coma; one with epilepsia partialis continua), four had stiff-person syndrome (one with seizures and limbic involvement), and two had opsoclonus-myoclonus. Overall, 12 of 15 patients for whom treatment and outcome were assessable had full (three patients) or partial (nine patients) response to immunotherapy or symptomatic treatment, and three died. Patients' antibodies caused a selective reduction of GABA A receptor clusters at synapses, but not along dendrites, without altering NMDA receptors and gephyrin (a protein that anchors the GABA A receptor). Interpretation High titres of serum and CSF GABA A receptor antibodies are associated with a severe form of encephalitis with seizures, refractory status epilepticus, or both. The antibodies cause a selective reduction of synaptic GABA A receptors. The disorder often occurs with GABAergic and other coexisting autoimmune disorders and is potentially treatable. Funding The National Institutes of Health, the McKnight Neuroscience of Brain Disorders, the Fondo de Investigaciones Sanitarias, Fundacio la Marato de TV3, the Netherlands Organisation for Scientific Research (Veni-incentive), the Dutch Epilepsy Foundation.