FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1590163747> ?p ?o ?g. }

• W1590163747 endingPage "284" @default.
• W1590163747 startingPage "267" @default.
• W1590163747 abstract "Key points During neuronal development synaptic events mediated by GABA A receptors are progressively reduced in their duration, allowing for rapid and precise network function. Here we focused on ventrobasal thalamocortical neurones, which contribute to behaviourally relevant oscillations between thalamus and cortex. We demonstrate that the developmental decrease in the duration of inhibitory phasic events results predominantly from a precisely timed loss of locally produced neurosteroids, which act as positive allosteric modulators of the GABA A receptor. The mature thalamus retains the ability to synthesise neurosteroids, thus preserving the capacity to enhance both phasic and tonic inhibition, mediated by synaptic and extrasynaptic GABA A receptors, respectively, in physiological and pathophysiological scenarios associated with perturbed neurosteroid levels. Our data establish a potent, endogenous mechanism to locally regulate the GABA A receptor function and thereby influence thalamocortical activity. Abstract During brain development the duration of miniature inhibitory postsynaptic currents (mIPSCs) mediated by GABA A receptors (GABA A Rs) progressively reduces, to accommodate the temporal demands required for precise network activity. Conventionally, this synaptic plasticity results from GABA A R subunit reorganisation. In particular, in certain developing neurones synaptic α2‐GABA A Rs are replaced by α1‐GABA A Rs. However, in thalamocortical neurones of the mouse ventrobasal (VB) thalamus, the major alteration to mIPSC kinetics occurs on postnatal (P) day 10, some days prior to the GABA A R isoform change. Here, whole‐cell voltage‐clamp recordings from VB neurones of mouse thalamic slices revealed that early in postnatal development (P7–P8), the mIPSC duration is prolonged by local neurosteroids acting in a paracrine or autocrine manner to enhance GABA A R function. However, by P10, this neurosteroid ‘tone’ rapidly dissipates, thereby producing brief mIPSCs. This plasticity results from a lack of steroid substrate as pre‐treatment of mature thalamic slices (P20–24) with the GABA A R‐inactive precursor 5α‐dihydroprogesterone (5α‐DHP) resulted in markedly prolonged mIPSCs and a greatly enhanced tonic conductance, mediated by synaptic and extrasynaptic GABA A Rs, respectively. In summary, endogenous neurosteroids profoundly influence GABAergic neurotransmission in developing VB neurones and govern a transition from slow to fast phasic synaptic events. Furthermore, the retained capacity for steroidogenesis in the mature thalamus raises the prospect that certain physiological or pathophysiological conditions may trigger neurosteroid neosynthesis, thereby providing a local mechanism for fine‐tuning neuronal excitability." @default.
• W1590163747 created "2016-06-24" @default.
• W1590163747 creator A5015149435 @default.
• W1590163747 creator A5019556156 @default.
• W1590163747 creator A5043001756 @default.
• W1590163747 creator A5088172807 @default.
• W1590163747 date "2014-12-03" @default.
• W1590163747 modified "2023-09-30" @default.
• W1590163747 title "Developmentally regulated neurosteroid synthesis enhances GABAergic neurotransmission in mouse thalamocortical neurones" @default.
• W1590163747 cites W1561736958 @default.
• W1590163747 cites W1599325783 @default.
• W1590163747 cites W1606221819 @default.
• W1590163747 cites W1932365967 @default.
• W1590163747 cites W1965959842 @default.
• W1590163747 cites W1967751978 @default.
• W1590163747 cites W1968059634 @default.
• W1590163747 cites W1968579780 @default.
• W1590163747 cites W1968685262 @default.
• W1590163747 cites W1968705930 @default.
• W1590163747 cites W1974028588 @default.
• W1590163747 cites W1976707885 @default.
• W1590163747 cites W1977556590 @default.
• W1590163747 cites W1987332038 @default.
• W1590163747 cites W1987762375 @default.
• W1590163747 cites W1993180169 @default.
• W1590163747 cites W1997828916 @default.
• W1590163747 cites W1999032965 @default.
• W1590163747 cites W2001728969 @default.
• W1590163747 cites W2011962541 @default.
• W1590163747 cites W2015330206 @default.
• W1590163747 cites W2020147365 @default.
• W1590163747 cites W2020165167 @default.
• W1590163747 cites W2022549781 @default.
• W1590163747 cites W2024344189 @default.
• W1590163747 cites W2037605765 @default.
• W1590163747 cites W2040091808 @default.
• W1590163747 cites W2042599546 @default.
• W1590163747 cites W2043385322 @default.
• W1590163747 cites W2044609602 @default.
• W1590163747 cites W2049075326 @default.
• W1590163747 cites W2050347923 @default.
• W1590163747 cites W2050393788 @default.
• W1590163747 cites W2052906514 @default.
• W1590163747 cites W2055180835 @default.
• W1590163747 cites W2055973066 @default.
• W1590163747 cites W2059941994 @default.
• W1590163747 cites W2061028746 @default.
• W1590163747 cites W2061947653 @default.
• W1590163747 cites W2066844700 @default.
• W1590163747 cites W2067267293 @default.
• W1590163747 cites W2068352644 @default.
• W1590163747 cites W2070510853 @default.
• W1590163747 cites W2072962057 @default.
• W1590163747 cites W2082076549 @default.
• W1590163747 cites W2084793167 @default.
• W1590163747 cites W2088232735 @default.
• W1590163747 cites W2091060078 @default.
• W1590163747 cites W2093634879 @default.
• W1590163747 cites W2100470385 @default.
• W1590163747 cites W2104543408 @default.
• W1590163747 cites W2104834189 @default.
• W1590163747 cites W2113668852 @default.
• W1590163747 cites W2118063127 @default.
• W1590163747 cites W2125250960 @default.
• W1590163747 cites W2128784337 @default.
• W1590163747 cites W2132069965 @default.
• W1590163747 cites W2132457456 @default.
• W1590163747 cites W2134064032 @default.
• W1590163747 cites W2136019568 @default.
• W1590163747 cites W2137471600 @default.
• W1590163747 cites W2138001567 @default.
• W1590163747 cites W2143178821 @default.
• W1590163747 cites W2145208959 @default.
• W1590163747 cites W2145939867 @default.
• W1590163747 cites W2154889134 @default.
• W1590163747 cites W2163215105 @default.
• W1590163747 cites W2165654705 @default.
• W1590163747 cites W2168014274 @default.
• W1590163747 cites W2170755395 @default.
• W1590163747 cites W2320983896 @default.
• W1590163747 cites W4245117662 @default.
• W1590163747 cites W4301495396 @default.
• W1590163747 doi "https://doi.org/10.1113/jphysiol.2014.280263" @default.
• W1590163747 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4293067" @default.
• W1590163747 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25556800" @default.
• W1590163747 hasPublicationYear "2014" @default.
• W1590163747 type Work @default.
• W1590163747 sameAs 1590163747 @default.
• W1590163747 citedByCount "18" @default.
• W1590163747 countsByYear W15901637472016 @default.
• W1590163747 countsByYear W15901637472017 @default.
• W1590163747 countsByYear W15901637472018 @default.
• W1590163747 countsByYear W15901637472019 @default.
• W1590163747 countsByYear W15901637472020 @default.
• W1590163747 countsByYear W15901637472021 @default.
• W1590163747 crossrefType "journal-article" @default.
• W1590163747 hasAuthorship W1590163747A5015149435 @default.
• W1590163747 hasAuthorship W1590163747A5019556156 @default.

• next