Changing properties of GABA(A) receptor-mediated signaling during early neocortical development. Owens, D F, Liu, X, & Kriegstein, A R J Neurophysiol, 82(2):570–583, United States, August, 1999. abstract bibtex Evidence from several brain regions suggests gamma-aminobutyric acid (GABA) can exert a trophic influence during development, expanding the role of this amino acid beyond its function as an inhibitory neurotransmitter. Proliferating precursor cells in the neocortical ventricular zone (VZ) express functional GABA(A) receptors as do immature postmigratory neurons in the developing cortical plate (CP); however, GABA(A) receptor properties in these distinct cell populations have not been compared. Using electrophysiological techniques in embryonic and early postnatal neocortex, we find that GABA(A) receptors expressed by VZ cells have a higher apparent affinity for GABA and are relatively insensitive to receptor desensitization compared with neurons in the CP. GABA-induced current magnitude increases with maturation with the smallest responses found in recordings from precursor cells in the VZ. No evidence was found that GABA(A) receptors on VZ cells are activated synaptically, consistent with previous data suggesting that these receptors are activated in a paracrine fashion by nonsynaptically released ligand. After neurons are born and migrate to the CP, they begin to demonstrate spontaneous synaptic activity, the majority of which is GABA(A) mediated. These spontaneous GABA(A) postsynaptic currents (sPSCs) first were detected at embryonic day 18 (E18). At birth, approximately 50% of recordings from cortical neurons demonstrated GABA(A)-mediated sPSCs, and this value increased with age. GABA(A)-mediated sPSCs were action potential dependent and arose from local GABAergic interneurons. GABA application could evoke action potential-dependent PSCs in neonatal cortical neurons, suggesting that during the first few postnatal days, GABA can act as an excitatory neurotransmitter. Finally, N-methyl-D-aspartate (NMDA)- but not non-NMDA-mediated sPSCs were also present in early postnatal neurons. These events were not observed in cells voltage clamped at negative holding potentials (-60 to -70 mV) but were evident when the holding potential was set at positive values (+30 to +60 mV). Together these results provide evidence for the early maturation of GABAergic communication in the neocortex and a functional change in GABA(A)-receptor properties between precursor cells and early postmitotic neurons. The change in GABA(A)-receptor properties may reflect the shift from paracrine to synaptic receptor activation.
@ARTICLE{Owens1999-bd,
title = "Changing properties of {GABA(A}) receptor-mediated signaling
during early neocortical development",
author = "Owens, D F and Liu, X and Kriegstein, A R",
abstract = "Evidence from several brain regions suggests gamma-aminobutyric
acid (GABA) can exert a trophic influence during development,
expanding the role of this amino acid beyond its function as an
inhibitory neurotransmitter. Proliferating precursor cells in the
neocortical ventricular zone (VZ) express functional GABA(A)
receptors as do immature postmigratory neurons in the developing
cortical plate (CP); however, GABA(A) receptor properties in
these distinct cell populations have not been compared. Using
electrophysiological techniques in embryonic and early postnatal
neocortex, we find that GABA(A) receptors expressed by VZ cells
have a higher apparent affinity for GABA and are relatively
insensitive to receptor desensitization compared with neurons in
the CP. GABA-induced current magnitude increases with maturation
with the smallest responses found in recordings from precursor
cells in the VZ. No evidence was found that GABA(A) receptors on
VZ cells are activated synaptically, consistent with previous
data suggesting that these receptors are activated in a paracrine
fashion by nonsynaptically released ligand. After neurons are
born and migrate to the CP, they begin to demonstrate spontaneous
synaptic activity, the majority of which is GABA(A) mediated.
These spontaneous GABA(A) postsynaptic currents (sPSCs) first
were detected at embryonic day 18 (E18). At birth, approximately
50\% of recordings from cortical neurons demonstrated
GABA(A)-mediated sPSCs, and this value increased with age.
GABA(A)-mediated sPSCs were action potential dependent and arose
from local GABAergic interneurons. GABA application could evoke
action potential-dependent PSCs in neonatal cortical neurons,
suggesting that during the first few postnatal days, GABA can act
as an excitatory neurotransmitter. Finally, N-methyl-D-aspartate
(NMDA)- but not non-NMDA-mediated sPSCs were also present in
early postnatal neurons. These events were not observed in cells
voltage clamped at negative holding potentials (-60 to -70 mV)
but were evident when the holding potential was set at positive
values (+30 to +60 mV). Together these results provide evidence
for the early maturation of GABAergic communication in the
neocortex and a functional change in GABA(A)-receptor properties
between precursor cells and early postmitotic neurons. The change
in GABA(A)-receptor properties may reflect the shift from
paracrine to synaptic receptor activation.",
journal = "J Neurophysiol",
volume = 82,
number = 2,
pages = "570--583",
month = aug,
year = 1999,
address = "United States",
language = "en"
}
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Proliferating precursor cells in the neocortical ventricular zone (VZ) express functional GABA(A) receptors as do immature postmigratory neurons in the developing cortical plate (CP); however, GABA(A) receptor properties in these distinct cell populations have not been compared. Using electrophysiological techniques in embryonic and early postnatal neocortex, we find that GABA(A) receptors expressed by VZ cells have a higher apparent affinity for GABA and are relatively insensitive to receptor desensitization compared with neurons in the CP. GABA-induced current magnitude increases with maturation with the smallest responses found in recordings from precursor cells in the VZ. No evidence was found that GABA(A) receptors on VZ cells are activated synaptically, consistent with previous data suggesting that these receptors are activated in a paracrine fashion by nonsynaptically released ligand. After neurons are born and migrate to the CP, they begin to demonstrate spontaneous synaptic activity, the majority of which is GABA(A) mediated. These spontaneous GABA(A) postsynaptic currents (sPSCs) first were detected at embryonic day 18 (E18). At birth, approximately 50% of recordings from cortical neurons demonstrated GABA(A)-mediated sPSCs, and this value increased with age. GABA(A)-mediated sPSCs were action potential dependent and arose from local GABAergic interneurons. GABA application could evoke action potential-dependent PSCs in neonatal cortical neurons, suggesting that during the first few postnatal days, GABA can act as an excitatory neurotransmitter. Finally, N-methyl-D-aspartate (NMDA)- but not non-NMDA-mediated sPSCs were also present in early postnatal neurons. These events were not observed in cells voltage clamped at negative holding potentials (-60 to -70 mV) but were evident when the holding potential was set at positive values (+30 to +60 mV). Together these results provide evidence for the early maturation of GABAergic communication in the neocortex and a functional change in GABA(A)-receptor properties between precursor cells and early postmitotic neurons. The change in GABA(A)-receptor properties may reflect the shift from paracrine to synaptic receptor activation.","journal":"J Neurophysiol","volume":"82","number":"2","pages":"570–583","month":"August","year":"1999","address":"United States","language":"en","bibtex":"@ARTICLE{Owens1999-bd,\n title = \"Changing properties of {GABA(A}) receptor-mediated signaling\n during early neocortical development\",\n author = \"Owens, D F and Liu, X and Kriegstein, A R\",\n abstract = \"Evidence from several brain regions suggests gamma-aminobutyric\n acid (GABA) can exert a trophic influence during development,\n expanding the role of this amino acid beyond its function as an\n inhibitory neurotransmitter. Proliferating precursor cells in the\n neocortical ventricular zone (VZ) express functional GABA(A)\n receptors as do immature postmigratory neurons in the developing\n cortical plate (CP); however, GABA(A) receptor properties in\n these distinct cell populations have not been compared. Using\n electrophysiological techniques in embryonic and early postnatal\n neocortex, we find that GABA(A) receptors expressed by VZ cells\n have a higher apparent affinity for GABA and are relatively\n insensitive to receptor desensitization compared with neurons in\n the CP. GABA-induced current magnitude increases with maturation\n with the smallest responses found in recordings from precursor\n cells in the VZ. No evidence was found that GABA(A) receptors on\n VZ cells are activated synaptically, consistent with previous\n data suggesting that these receptors are activated in a paracrine\n fashion by nonsynaptically released ligand. After neurons are\n born and migrate to the CP, they begin to demonstrate spontaneous\n synaptic activity, the majority of which is GABA(A) mediated.\n These spontaneous GABA(A) postsynaptic currents (sPSCs) first\n were detected at embryonic day 18 (E18). At birth, approximately\n 50\\% of recordings from cortical neurons demonstrated\n GABA(A)-mediated sPSCs, and this value increased with age.\n GABA(A)-mediated sPSCs were action potential dependent and arose\n from local GABAergic interneurons. GABA application could evoke\n action potential-dependent PSCs in neonatal cortical neurons,\n suggesting that during the first few postnatal days, GABA can act\n as an excitatory neurotransmitter. Finally, N-methyl-D-aspartate\n (NMDA)- but not non-NMDA-mediated sPSCs were also present in\n early postnatal neurons. These events were not observed in cells\n voltage clamped at negative holding potentials (-60 to -70 mV)\n but were evident when the holding potential was set at positive\n values (+30 to +60 mV). Together these results provide evidence\n for the early maturation of GABAergic communication in the\n neocortex and a functional change in GABA(A)-receptor properties\n between precursor cells and early postmitotic neurons. The change\n in GABA(A)-receptor properties may reflect the shift from\n paracrine to synaptic receptor activation.\",\n journal = \"J Neurophysiol\",\n volume = 82,\n number = 2,\n pages = \"570--583\",\n month = aug,\n year = 1999,\n address = \"United States\",\n language = \"en\"\n}\n\n","author_short":["Owens, D F","Liu, X","Kriegstein, A R"],"key":"Owens1999-bd","id":"Owens1999-bd","bibbaseid":"owens-liu-kriegstein-changingpropertiesofgabaareceptormediatedsignalingduringearlyneocorticaldevelopment-1999","role":"author","urls":{},"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bibbase.org/f/EJMp3HRuxirjxpcXh/references.bib","dataSources":["sAFYeB74DpbdXM9NN","4zx9n2tbeLTix3Wxr","k3cdWrThyTh5o59Rm","hq9pebjzmsTuyxGGx","h8Atv2SAy4PmShg5j"],"keywords":[],"search_terms":["changing","properties","gaba","receptor","mediated","signaling","during","early","neocortical","development","owens","liu","kriegstein"],"title":"Changing properties of GABA(A) receptor-mediated signaling during early neocortical development","year":1999}