Article

Membrane potential dynamics of GABAergic neurons in the barrel cortex of behaving mice.

Laboratory of Sensory Processing, Brain Mind Institute, Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Neuron (Impact Factor: 15.98). 02/2010; 65(3):422-35. DOI: 10.1016/j.neuron.2010.01.006
Source: PubMed

ABSTRACT Computations in cortical circuits are mediated by synaptic interactions between excitatory and inhibitory neurons, and yet we know little about their activity in awake animals. Here, through single and dual whole-cell recordings combined with two-photon microscopy in the barrel cortex of behaving mice, we directly compare the synaptically driven membrane potential dynamics of inhibitory and excitatory layer 2/3 neurons. We find that inhibitory neurons depolarize synchronously with excitatory neurons, but they are much more active with differential contributions of two classes of inhibitory neurons during different brain states. Fast-spiking GABAergic neurons dominate during quiet wakefulness, but during active wakefulness Non-fast-spiking GABAergic neurons depolarize, firing action potentials at increased rates. Sparse uncorrelated action potential firing in excitatory neurons is driven by fast, large, and cell-specific depolarization. In contrast, inhibitory neurons fire correlated action potentials at much higher frequencies driven by slower, smaller, and broadly synchronized depolarization.

0 Followers
 · 
175 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Familial hemiplegic migraine type 1 (FHM1) is caused by gain-of-function mutations in CaV2.1 (P/Q-type) Ca(2+) channels. Knockin (KI) mice carrying the FHM1 R192Q missense mutation show enhanced cortical excitatory synaptic transmission at pyramidal cell synapses but unaltered cortical inhibitory neurotransmission at fast-spiking interneuron synapses. Enhanced cortical glutamate release was shown to cause the facilitation of cortical spreading depression (CSD) in R192Q KI mice. It, however, remains unknown how other FHM1 mutations affect cortical synaptic transmission. Here, we studied neurotransmission in cortical neurons in microculture from KI mice carrying the S218L mutation, which causes a severe FHM syndrome in humans and an allele-dosage dependent facilitation of experimental CSD in KI mice, which is larger than that caused by the R192Q mutation. We show gain-of-function of excitatory neurotransmission, due to increased action-potential evoked Ca(2+) influx and increased probability of glutamate release at pyramidal cell synapses, but unaltered inhibitory neurotransmission at multipolar interneuron synapses in S218L KI mice. In contrast with the larger gain-of-function of neuronal CaV2.1 current in homozygous than heterozygous S218L KI mice, the gain-of-function of evoked glutamate release, the paired-pulse ratio and the Ca(2+) dependence of the excitatory postsynaptic current were similar in homozygous and heterozygous S218L KI mice, suggesting compensatory changes in the homozygous mice. Furthermore, we reveal a unique feature of S218L KI cortical synapses which is the presence of a fraction of mutant CaV2.1 channels being open at resting potential. Our data suggest that, while the gain-of-function of evoked glutamate release may explain the facilitation of CSD in heterozygous S218L KI mice, the further facilitation of CSD in homozygous S218L KI mice is due to other CaV2.1-dependent mechanisms, that likely include Ca(2+) influx at voltages sub-threshold for action potential generation.
    Frontiers in Cellular Neuroscience 02/2015; 9. DOI:10.3389/fncel.2015.00008 · 4.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neurons are polarized functional units. The somatodendritic compartment receives and integrates synaptic inputs while the axon relays relevant synaptic information in form of action potentials (APs) across long distance. Despite this well accepted notion, recent research has shown that, under certain circumstances, the axon can also generate APs independent of synaptic inputs at axonal sites distal from the soma. These ectopic APs travel both toward synaptic terminals and antidromically toward the soma. This unusual form of neuronal communication seems to preferentially occur in cortical inhibitory interneurons following a period of intense neuronal activity and might have profound implications for neuronal information processing. Here we show that trains of ectopically generated APs can be induced in a large portion of neocortical layer 2/3 GABAergic interneurons following a somatic depolarization inducing hundreds of APs. Sparsely occurring ectopic spikes were also observed in a large portion of layer 1 interneurons even in absence of prior somatic depolarization. Remarkably, we found that interneurons which produce ectopic APs display specific membrane and morphological properties significantly different from the remaining GABAergic cells and may therefore represent a functionally unique interneuronal subpopulation.
    Neural Plasticity 01/2015; 2015:608141. DOI:10.1155/2015/608141 · 3.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Spontaneous and sensory-evoked cortical activity is highly state-dependent, yet relatively little is known about transitions between distinct waking states. Patterns of activity in mouse V1 differ dramatically between quiescence and locomotion, but this difference could be explained by either motor feedback or a change in arousal levels. We recorded single cells and local field potentials from area V1 in mice head-fixed on a running wheel and monitored pupil diameter to assay arousal. Using naturally occurring and induced state transitions, we dissociated arousal and locomotion effects in V1. Arousal suppressed spontaneous firing and strongly altered the temporal patterning of population activity. Moreover, heightened arousal increased the signal-to-noise ratio of visual responses and reduced noise correlations. In contrast, increased firing in anticipation of and during movement was attributable to locomotion effects. Our findings suggest complementary roles of arousal and locomotion in promoting functional flexibility in cortical circuits. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neuron 04/2015; DOI:10.1016/j.neuron.2015.03.028 · 15.98 Impact Factor

Full-text (2 Sources)

Download
92 Downloads
Available from
Jun 5, 2014