Dataset Information

Expression of functional inhibitory neurotransmitter transporters GlyT1, GAT-1, and GAT-3 by astrocytes of inferior colliculus and hippocampus.

ABSTRACT: Neuronal inhibition is mediated by glycine and/or GABA. Inferior colliculus (IC) neurons receive glycinergic and GABAergic inputs, whereas inhibition in hippocampus (HC) predominantly relies on GABA. Astrocytes heterogeneously express neurotransmitter transporters and are expected to adapt to the local requirements regarding neurotransmitter homeostasis. Here we analyzed the expression of inhibitory neurotransmitter transporters in IC and HC astrocytes using whole-cell patch-clamp and single-cell reverse transcription-PCR. We show that most astrocytes in both regions expressed functional glycine transporters (GlyTs). Activation of these transporters resulted in an inward current (IGly) that was sensitive to the competitive GlyT1 agonist sarcosine. Astrocytes exhibited transcripts for GlyT1 but not for GlyT2. Glycine did not alter the membrane resistance (RM) arguing for the absence of functional glycine receptors (GlyRs). Thus, IGly was mainly mediated by GlyT1. Similarly, we found expression of functional GABA transporters (GATs) in all IC astrocytes and about half of the HC astrocytes. These transporters mediated an inward current (IGABA) that was sensitive to the competitive GAT-1 and GAT-3 antagonists NO711 and SNAP5114, respectively. Accordingly, transcripts for GAT-1 and GAT-3 were found but not for GAT-2 and BGT-1. Only in hippocampal astrocytes, GABA transiently reduced RM demonstrating the presence of GABAA receptors (GABAARs). However, IGABA was mainly not contaminated by GABAAR-mediated currents as RM changes vanished shortly after GABA application. In both regions, IGABA was stronger than IGly. Furthermore, in HC the IGABA/IGly ratio was larger compared to IC. Taken together, our results demonstrate that astrocytes are heterogeneous across and within distinct brain areas. Furthermore, we could show that the capacity for glycine and GABA uptake varies between both brain regions.

SUBMITTER: Ghirardini E

PROVIDER: S-EPMC5785846 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Expression of functional inhibitory neurotransmitter transporters GlyT1, GAT-1, and GAT-3 by astrocytes of inferior colliculus and hippocampus.

Ghirardini Elsa E Wadle Simon L SL Augustin Vanessa V Becker Jasmin J Brill Sina S Hammerich Julia J Seifert Gerald G Stephan Jonathan J

Molecular brain 20180125 1

Neuronal inhibition is mediated by glycine and/or GABA. Inferior colliculus (IC) neurons receive glycinergic and GABAergic inputs, whereas inhibition in hippocampus (HC) predominantly relies on GABA. Astrocytes heterogeneously express neurotransmitter transporters and are expected to adapt to the local requirements regarding neurotransmitter homeostasis. Here we analyzed the expression of inhibitory neurotransmitter transporters in IC and HC astrocytes using whole-cell patch-clamp and single-cel ...[more]

PMID: 29370841

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Project description:The medial geniculate body (MGB) is the thalamic center of the auditory lemniscal pathway. The ventral division of MGB (MGV) receives excitatory and inhibitory inputs from the inferior colliculus (IC). MGV is involved in auditory attention by processing descending excitatory and inhibitory inputs from the auditory cortex (AC) and reticular thalamic nucleus (RTN), respectively. However, detailed mechanisms of the integration of different inputs in a single MGV neuron remain unclear. Kv4.2 is one of the isoforms of the Shal-related subfamily of potassium voltage-gated channels that are expressed in MGB. Since potassium channel is important for shaping synaptic current and spike waveforms, subcellular distribution of Kv4.2 is likely important for integration of various inputs. Here, we aimed to examine the detailed distribution of Kv4.2, in MGV neurons to understand its specific role in auditory attention. We found that Kv4.2 mRNA was expressed in most MGV neurons. At the protein level, Kv4.2-immunopositive patches were sparsely distributed in both the dendrites and the soma of neurons. The postsynaptic distribution of Kv4.2 protein was confirmed using electron microscopy (EM). The frequency of contact with Kv4.2-immunopositive puncta was higher in vesicular glutamate transporter 2 (VGluT2)-positive excitatory axon terminals, which are supposed to be extending from the IC, than in VGluT1-immunopositive terminals, which are expected to be originating from the AC. VGluT2-immunopositive terminals were significantly larger than VGluT1-immunopositive terminals. Furthermore, EM showed that the terminals forming asymmetric synapses with Kv4.2-immunopositive MGV dendritic domains were significantly larger than those forming synapses with Kv4.2-negative MGV dendritic domains. In inhibitory axons either from the IC or from the RTN, the frequency of terminals that were in contact with Kv4.2-positive puncta was higher in IC than in RTN. In summary, our study demonstrated that the Kv4.2-immunopositive domains of the MGV dendrites received excitatory and inhibitory ascending auditory inputs preferentially from the IC, and not from the RTN or cortex. Our findings imply that time course of synaptic current and spike waveforms elicited by IC inputs is modified in the Kv4.2 domains.

Dataset Information

Expression of functional inhibitory neurotransmitter transporters GlyT1, GAT-1, and GAT-3 by astrocytes of inferior colliculus and hippocampus.

Publications

Expression of functional inhibitory neurotransmitter transporters GlyT1, GAT-1, and GAT-3 by astrocytes of inferior colliculus and hippocampus.

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