Journal ArticleDOI
Excitatory actions of gaba during development: the nature of the nurture.
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TLDR
This work proposes that GABA becomes inhibitory by the delayed expression of a chloride exporter, leading to a negative shift in the reversal potential for choride ions, and provides a solution to the problem of how to excite developing neurons to promote growth and synapse formation.Abstract:
In the immature brain, GABA (gamma-aminobutyric acid) is excitatory, and GABA-releasing synapses are formed before glutamatergic contacts in a wide range of species and structures. GABA becomes inhibitory by the delayed expression of a chloride exporter, leading to a negative shift in the reversal potential for choride ions. I propose that this mechanism provides a solution to the problem of how to excite developing neurons to promote growth and synapse formation while avoiding the potentially toxic effects of a mismatch between GABA-mediated inhibition and glutamatergic excitation. As key elements of this cascade are activity dependent, the formation of inhibition adds an element of nurture to the construction of cortical networks.read more
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Transcript-Specific Associations of SLC12A5 (KCC2) in Human Prefrontal Cortex with Development, Schizophrenia, and Affective Disorders
Ran Tao,Chao Li,Erin N. Newburn,Tianzhang Ye,Tianzhang Ye,Barbara K. Lipska,Mary M. Herman,Daniel R. Weinberger,Joel E. Kleinman,Thomas M. Hyde +9 more
TL;DR: The expression levels of four relatively abundant truncated splice variants, including three novel transcripts (ΔEXON6, EXON2B, and EXON6B) and one previously described transcript (AK098371), are measured in a large human cohort of nonpsychiatric controls across the lifespan, and in patients with schizophrenia and affective disorders.
Journal ArticleDOI
Chloride transporters and GABA polarity in developmental, neurological and psychiatric conditions.
TL;DR: Current knowledge on chloride transporter expression and activity regulation is reviewed and the intriguing potential for existing and future interventions to support chloride homeostasis across a wide range of mental disorders and neurological conditions is highlighted.
Journal ArticleDOI
Chronic stress shifts the GABA reversal potential in the hippocampus and increases seizure susceptibility
Georgina MacKenzie,Jamie Maguire +1 more
TL;DR: A potential mechanism underlying changes in neuronal excitability in the hippocampus following chronic stress, involving a shift in the reversal potential for GABA associated with a dephosphorylation of the potassium chloride co-transporter, KCC2, is demonstrated.
Journal ArticleDOI
GABAergic Signaling at Mossy Fiber Synapses in Neonatal Rat Hippocampus
TL;DR: It is shown that, during the first postnatal week, stimulation of granule cells in the dentate gyrus gave rise to monosynaptic GABAA-mediated responses in principal cells and in interneurons, indicating that GABAergic signaling may play a crucial role in tuning hippocampal network during postnatal development.
Journal ArticleDOI
Transition to seizures in the isolated immature mouse hippocampus: a switch from dominant phasic inhibition to dominant phasic excitation.
TL;DR: There is a change in the interaction between afferent synaptic inhibition, and afferent and intrinsic excitatory processes in pyramidal neurons and interneurons, with maintained inhibition and increasing, entrained ‘overpowering’ excitation during the transition to seizure.
References
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Journal ArticleDOI
The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation.
Claudio Rivera,Juha Voipio,John A. Payne,Eva Ruusuvuori,Hannele Lahtinen,Karri Lamsa,Ulla Pirvola,Mart Saarma,Kai Kaila +8 more
TL;DR: It is shown that, in pyramidal neurons of the rat hippocampus, the ontogenetic change in GABAA-mediated responses from depolarizing to hyperpolarizing is coupled to a developmental induction of the expression of the neuronal Cl−-extruding K+/Cl − co-transporter, KCC2 (ref. 7).
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Gamma (40-100 Hz) oscillation in the hippocampus of the behaving rat
TL;DR: It is suggested that gamma oscillation emerges from an interaction between intrinsic oscillatory properties of interneurons and the network properties of the dentate gyrus and that Gamma oscillation in the CA3-CA1 circuitry is suppressed by either the hilar region or the entorhinal cortex.
Journal ArticleDOI
Synaptic Assembly of the Brain in the Absence of Neurotransmitter Secretion
Matthijs Verhage,Ascanio S. Maia,Jaap J. Plomp,Arjen B. Brussaard,J H Heeroma,H. Vermeer,Ruud F. Toonen,Robert E. Hammer,T K van den Berg,Markus Missler,Hans J. Geuze,Thomas C. Südhof +11 more
TL;DR: Synaptic connectivity does not depend on neurotransmitter secretion, but its maintenance does, and neurotransmitter secretion probably functions to validate already established synaptic connections.
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Giant synaptic potentials in immature rat CA3 hippocampal neurones.
TL;DR: In neurones in which evoked GDPs were blocked by bicuculline, a NMDA‐mediated component was revealed by increasing the strength or the frequency of stimulation, and during the second week of postnatal life, superfusion with bicuciulline induced, as in adult slices, interictal discharges.