2020
DOI: 10.3389/fncel.2020.00009
|View full text |Cite
|
Sign up to set email alerts
|

A Reappraisal of GAT-1 Localization in Neocortex

Abstract: γ-Aminobutyric acid (GABA) transporter (GAT)-1, the major GABA transporter in the brain, plays a key role in modulating GABA signaling and is involved in the pathophysiology of several neuropsychiatric diseases, including epilepsy. The original description of GAT-1 as a neuronal transporter has guided the interpretation of the findings of all physiological, pharmacological, genetic, or clinical studies. However, evidence published in the past few years, some of which is briefly reviewed herein, does not seem t… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

2
11
0

Year Published

2021
2021
2024
2024

Publication Types

Select...
6
3

Relationship

1
8

Authors

Journals

citations
Cited by 32 publications
(13 citation statements)
references
References 60 publications
2
11
0
Order By: Relevance
“…Immunostaining for HA confirmed our ability to reintroduce Gat1 specifically in SNc DA neurons (Figure 4A). We observed Gat1-HA throughout the axons of SNc DA neurons in dorsal striatum (Figure S3A), consistent with Gat1’s usual presynaptic distribution (Scimemi, 2014; Uchigashima et al, 2016; Fattorini et al, 2020). Importantly, exogenous expression of Gat1-HA in SNc DA neurons of Gat1 cKO DA mice fully restored GABAergic signaling (Figures 4C and 4H–J), as oIPSCs were indistinguishable from those recorded in wild type controls in amplitude (1.49 ± 0.23 nA; n = 14 SPNs from 4 mice), synaptic latency (2.25 ± 0.18 ms) and rise time (2.14 ± 0.24 ms; all p > 0.05 vs. control, Mann– Whitney).…”
Section: Resultssupporting
confidence: 77%
See 1 more Smart Citation
“…Immunostaining for HA confirmed our ability to reintroduce Gat1 specifically in SNc DA neurons (Figure 4A). We observed Gat1-HA throughout the axons of SNc DA neurons in dorsal striatum (Figure S3A), consistent with Gat1’s usual presynaptic distribution (Scimemi, 2014; Uchigashima et al, 2016; Fattorini et al, 2020). Importantly, exogenous expression of Gat1-HA in SNc DA neurons of Gat1 cKO DA mice fully restored GABAergic signaling (Figures 4C and 4H–J), as oIPSCs were indistinguishable from those recorded in wild type controls in amplitude (1.49 ± 0.23 nA; n = 14 SPNs from 4 mice), synaptic latency (2.25 ± 0.18 ms) and rise time (2.14 ± 0.24 ms; all p > 0.05 vs. control, Mann– Whitney).…”
Section: Resultssupporting
confidence: 77%
“…Immunostaining for HA confirmed our ability to reintroduce Gat1 specifically in SNc DA neurons (Figure 4A). We observed Gat1-HA throughout the axons of SNc DA neurons in dorsal striatum (Figure S3A), consistent with Gat1's usual presynaptic distribution (Scimemi, 2014;Uchigashima et al, 2016;Fattorini et al, 2020).…”
Section: Inhibitory Co-transmission Relies On Gat1-mediated Import Of Gabasupporting
confidence: 76%
“…Stoichiometry coefficients have been omitted in (16) for simplicity. The electrogenic sodium bicarbonate cotransporter (NBCe1) specifically implicated in glial metabolic and other functions, is another important candidate to be analyzed in the context of bistability since the reversal of the polarity of Δ V m would cause switching of the transport direction and in turn the whole-cell mode between alkalization and acidification of the cell itself, and consequently the immediate extracellular environment (Ransom, 2000). Of the other transporters potentially “vulnerable” to bistability let us mention the astrocytic GABA transporters (GAT1-GAT3) expressed in local cortical circuits (Fattorini, Melone, & Conti, 2020), (Zafar & Jabeen, 2018), modeled macroscopically as explicitly V m dependent (Hoshino, Kameno, Kubo, & Watanabe, 2020). ○ (I4), (S3) Glial encoding of [ K + ] o variations as a signal gets a distinct state – In the present understanding of the encoding capability of glial membrane, the glial V m with certain low-pass filtering capability (with τ m = C eff /g slope ≈ 10 ms for 20pF patch capacitance) close to linearly encodes [ K + ] o variations as a signal through ( V m – E K ).…”
Section: Discussion / I ~ Importance S – Significance N – Novelty U -...mentioning
confidence: 99%
“…Astrocytes express transporters for glutamate (GLT-1, GLAST) 38,39 and GABA (GAT-1, GAT-3) 40,41 at high levels. These transporters are a primary mechanism for neurotransmitter uptake in the CNS and astrocytic uptake of glutamate and GABA is critical for the finely tuned balance of excitation and inhibition in the cortex 32,38,[42][43][44] .…”
Section: Gabamentioning
confidence: 99%