Region and layer-specific expression of GABA receptor isoforms and KCC2 in developing cortex.

Introduction: γ-Aminobutyric acid (GABA) type A receptors (GABARs) are ligand-gated Cl-channels that mediate the bulk of inhibitory neurotransmission in the mature CNS and are targets of many drugs. During cortical development, GABAR-mediated signals are significantly modulated by changing subunit composition and expression of Cl-transporters as part of developmental processes and early network activity. To date, this developmental evolution has remained understudied, particularly at the level of cortical layer-specific changes.

GABA Receptor β3 Subunit Mutation N328D Heterozygous Knock-in Mice Have Lennox-Gastaut Syndrome.

Lennox-Gastaut Syndrome (LGS) is a developmental and epileptic encephalopathy (DEE) characterized by multiple seizure types, electroencephalogram (EEG) patterns, and cognitive decline. Its etiology has a prominent genetic component, including variants in that encodes the GABA receptor (GABAR) β subunit. LGS has an unknown pathophysiology, and few animal models are available for studying LGS.

Dendritic Inhibition by Shh Signaling-Dependent Stellate Cell Pool Is Critical for Motor Learning.

Cerebellar inhibitory interneurons are important regulators of neural circuit activity for diverse motor and nonmotor functions. The molecular layer interneurons (MLIs), consisting of basket cells (BCs) and stellate cells (SCs), provide dendritic and somatic inhibitory synapses onto Purkinje cells, respectively. They are sequentially generated in an inside-out pattern from Pax2 immature interneurons, which migrate from the prospective white matter to the ML of the cortex.

Loss of KCC2 in GABAergic Neurons Causes Seizures and an Imbalance of Cortical Interneurons.

K-Cl transporter KCC2 is an important regulator of neuronal development and neuronal function at maturity. Through its canonical transporter role, KCC2 maintains inhibitory responses mediated by γ-aminobutyric acid (GABA) type A receptors. During development, late onset of KCC2 transporter activity defines the period when depolarizing GABAergic signals promote a wealth of developmental processes.