5 research outputs found
GABAB receptors regulate extrasynaptic GABAA receptors
Tonic inhibitory GABAA receptor-mediated currents are observed in numerous cell types in the CNS, including thalamocortical neurons of the ventrobasal thalamus, dentate gyrus granule cells, and cerebellar granule cells. Here we show that in rat brain slices, activation of postsynaptic GABAB receptors enhances the magnitude of the tonic GABAA current recorded in these cell types via a pathway involving Gi/o G proteins, adenylate cyclase, and cAMP-dependent protein kinase. Using a combination of pharmacology and knockout mice, we show that this pathway is independent of potassium channels or GABA transporters. Furthermore, the enhancement in tonic current is sufficient to significantly alter the excitability of thalamocortical neurons. These results demonstrate for the first time a postsynaptic crosstalk between GABAB and GABAA receptors.peer-reviewe
Clinical and experimental insight into pathophysiology, comorbidity and therapy of absence seizures
Absence seizures in children and teenagers are generally considered relatively benign because of their non-convulsive nature and
the large incidence of remittance in early adulthood. Recent studies, however, show that 30% of children with absence seizures are
pharmaco-resistant and 60% are affected by severe neuropsychiatric comorbid conditions, including impairments in attention, cognition,
memory and mood. In particular, attention deficits can be detected before the epilepsy diagnosis, may persist even when
seizures are pharmacologically controlled and are aggravated by valproic acid monotherapy. New functional MRI-magnetoencephalography
and functional MRI-EEG studies provide conclusive evidence that changes in blood oxygenation level-dependent signal
amplitude and frequency in children with absence seizures can be detected in specific cortical networks at least 1 min before the
start of a seizure, spike-wave discharges are not generalized at seizure onset and abnormal cortical network states remain during
interictal periods. From a neurobiological perspective, recent electrical recordings and imaging of large neuronal ensembles with
single-cell resolution in non-anaesthetized models show that, in contrast to the predominant opinion, cortical mechanisms, rather
than an exclusively thalamic rhythmogenesis, are key in driving seizure ictogenesis and determining spike-wave frequency. [Excerpt from Abstract]peer-reviewe
Cortical drive and thalamic feed-forward inhibition control thalamic output synchrony during absence seizures
International audienceBehaviorally and pathologically relevant cortico-thalamo-cortical oscillations are driven by diverse interacting cell-intrinsic and synaptic processes. However, the mechanism that gives rise to the paroxysmal oscillations of absence seizures (ASs) remains unknown. Here we report that during ASs in behaving animals, cortico-thalamic excitation drives thalamic firing by preferentially eliciting tonic rather than T-type Ca 2+ channels (T-channels)-dependent burst firing in thalamocortical (TC) neurons, and by temporally framing thalamic output via feed-forward reticular thalamic (NRT)-to-TC neuron inhibition. In TC neurons, overall ictal firing is markedly reduced and bursts rarely occur. Moreover, block of T-channels in cortical and NRT neurons suppresses ASs, but in TC neurons has no effect on seizures or on ictal thalamic output synchrony. These results demonstrate ictal bidirectional cortico-thalamic communications and provide th