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Neuroactive steroids are potent modulators of gamma-aminobutyric acid type A receptors (GABAARs), and their behavioral effects are generally viewed in terms of altered inhibitory synaptic transmission. Here we report that, at concentrations known to occur in vivo, neuroactive steroids specifically enhance a tonic inhibitory conductance in central neurons(More)
N-methyl-D-aspartate receptors (NMDARs) are present at many excitatory glutamate synapses in the central nervous system and display unique properties that depend on their subunit composition. Biophysical, pharmacological and molecular methods have been used to determine the key features conferred by the various NMDAR subunits, and have helped to establish(More)
1. To investigate the origin and functional significance of a recently described tonic GABAA receptor-mediated conductance in cerebellar granule cells we have made recordings from cells in cerebellar slices from rats of different ages (postnatal days P4 to P28). 2. During development there was a dramatic change in the properties of GABA-mediated synaptic(More)
Many neurons receive a continuous, or 'tonic', synaptic input, which increases their membrane conductance, and so modifies the spatial and temporal integration of excitatory signals. In cerebellar granule cells, although the frequency of inhibitory synaptic currents is relatively low, the spillover of synaptically released GABA (gamma-aminobutyric acid)(More)
The timing of action potentials is an important determinant of information coding in the brain. The shape of the EPSP has a key influence on the temporal precision of spike generation. Here we use dynamic clamp recording and passive neuronal models to study how developmental changes in synaptic conductance waveform and intrinsic membrane properties combine(More)
Over the past two decades, research has identified extrasynaptic GABA(A) receptor populations that enable neurons to sense the low ambient GABA concentrations present in the extracellular space in order to generate a form of tonic inhibition not previously considered in studies of neuronal excitability. The importance of this tonic inhibition in regulating(More)
Many neurons express a multiplicity of GABAA receptor subunit isoforms. Despite having only a single source of inhibitory input, the cerebellar granule cell displays, at various stages of development, more than 10 different GABAA subunit types. This subunit diversity would be expected to result in significant receptor heterogeneity, yet the functional(More)
Two-pore domain potassium (K2P) channel expression is believed to underlie the developmental emergence of a potassium leak conductance [IK(SO)] in cerebellar granule neurons (CGNs), suggesting that K2P function is an important determinant of the input conductance and resting membrane potential. To investigate the role that different K2P channels may play in(More)
NMDA receptors (NMDARs) are thought to be tetrameric assemblies composed of NR1 and at least one type of NR2 subunit. The identity of the NR2 subunit (NR2A, -B, -C, -D) is critical in determining many of the functional properties of the receptor, such as channel conductance and deactivation time. Further diversity may arise from coassembly of more than one(More)
High-affinity extrasynaptic GABA(A) receptors (GABA(A)Rs) are a prominent feature of cerebellar granule neurons and thalamic relay neurons. In both cell types, the presence of synaptic glomeruli would be expected to promote activation of these GABA(A)Rs, contributing to phasic spillover-mediated currents and tonic inhibition. However, the precise role of(More)