Biomedical subjects

Didier Pinault

Publications and source records attributed to Didier Pinault.

5 recordsLinked to original sources

PubMed2006

Functional stabilization of weakened thalamic pacemaker channel regulation in rat absence epilepsy.

Aberrant function of pacemaker currents (Ih), carried by hyperpolarization-activated cation non-selective (HCN) channels, affects neuronal excitability and accompanies epilepsy, but its distinct roles in epileptogenesis and chronic epilepsy are unclear. We probed Ih function and subunit composition during both pre- and chronically epileptic stages in thalamocortical (TC) neurones of the Genetic Absence Epilepsy Rat from Strasbourg (GAERS). Voltage gating of Ih was unaltered in mature somatosensory TC cells, both in vivo and in vitro. However, the enhancement of Ih by phasic, near-physiological, cAMP pulses was diminished by approximately 40% and the half-maximal cAMP concentration increased by approximately 5-fold. This decreased responsiveness of Ih to its major cellular modulator preceded epilepsy onset in GAERS, persisted throughout the chronic state, and was accompanied by an enhanced expression of the cAMP-insensitive HCN1 channel mRNA (> 50%), without changes in the mRNA levels of HCN2 and HCN4. To assess for alterations in TC cell excitability, we monitored the slow up-regulation of Ih that is induced by Ca2+-triggered cAMP synthesis and important for terminating in vitro synchronized oscillations. Remarkably, repetitive rebound Ca2+ spikes evoked normal slow Ih up-regulation in mature GAERS neurones; that sufficed to attenuate spontaneous rhythmic burst discharges. These adaptive mechanisms occurred upstream of cAMP turnover and involved enhanced intracellular Ca2+ accumulation upon repetitive low-threshold Ca2+ discharges. Therefore, HCN channels appear to play a dual role in epilepsy. Weakened cAMP binding to HCN channels precedes, and likely promotes, epileptogenesis in GAERS, whereas compensatory mechanisms stabilizing Ih function contribute to the termination of spike-and-wave discharges in chronic epilepsy.

Animals↗

PubMed2006

Corticothalamic 5-9 Hz oscillations are more pro-epileptogenic than sleep spindles in rats.

Absence-related spike-and-wave discharges (SWDs) occur in the thalamocortical system during quiet wakefulness or drowsiness. In feline generalized penicillin epilepsy, SWDs develop from sleep spindles. In contrast, in genetic absence epilepsy rats from Strasbourg (GAERS), SWDs develop from wake-related 5-9 Hz oscillations, which are distinct from spindle oscillations (7-15 Hz). Since these two oscillation types share common frequency bands and may contribute to SWD genesis, it is important to compare their thalamic cellular mechanisms. Under neuroleptic analgesia, in GAERS and control non-epileptic rats barbiturates abolished both SWDs and 5-9 Hz oscillations but increased the incidence of spindle-like oscillations. Within the thalamocortical circuit 5-9 Hz oscillations occurred more coherently than spindle-like oscillations. Intracellular events associated with 5-9 Hz and spindle-like oscillations were distinctively different in both thalamic relay and reticular neurons. In both cell types, SWDs and 5-9 Hz oscillations emerged from a significantly more depolarized membrane potential than spindle-like oscillations. In relay neurons, 5-9 Hz oscillations were mainly characterized by a rhythmic depolarization, which occurred during a tonic hyperpolarization and which could trigger an apparent low-threshold Ca2+ potential, whereas spindle-like oscillations were characterized by a rhythmic hyperpolarization. In reticular cells, SWDs and 5-9 Hz oscillations occurred during a tonic hyperpolarization, whereas spindle-like oscillations occurred during a long-lasting depolarizing envelope. The difference in the intracellular events between 5-9 Hz and spindle-like oscillations and similarities between 5-9 Hz oscillations and SWDs indicate that in GAERS, 5-9 Hz oscillations are more pro-epileptogenic than spindle-like oscillations. In conclusion, the present study strongly supports the hypothesis that SWDs in GAERS are generated by a wake-related corticothalamic resonance, and not by sleep-related, hypersynchronous, spindle-like activity originating in the thalamus.

Action Potentials↗

PubMed2005

A new stabilizing craniotomy-duratomy technique for single-cell anatomo-electrophysiological exploration of living intact brain networks.

Standard large craniotomies induce undesirable brain motions during intracellular recordings in whole animal preparations. Practically all of the papers available in the literature outline a number of specific methodological approaches designed to avoid this inconvenience. Our study describes a new craniotomy-duratomy, which consists of the maintenance of a thin bone membrane and dura mater surrounding the small hole opened for lowering the recording micropipette. This new surgical preparation avoids brain movements by keeping the brain's volume constant within the cranial cavity and does not require additional technical procedures. It is an all-purpose surgical technique, although it was developed in anaesthetized rats while studying spatio-temporal dynamics of cellular interactions associated with thalamocortical oscillations. It significantly improves both the precision of stereotaxic approaches and the success rate of single-cell recordings (e.g., current-clamp intracellular and paired recordings) compared to standard craniotomy/electrophysiology techniques.

Animals↗

PubMed2004

The thalamic reticular nucleus: structure, function and concept.

On the basis of theoretical, anatomical, psychological and physiological considerations, Francis Crick (1984) proposed that, during selective attention, the thalamic reticular nucleus (TRN) controls the internal attentional searchlight that simultaneously highlights all the neural circuits called on by the object of attention. In other words, he submitted that during either perception, or the preparation and execution of any cognitive and/or motor task, the TRN sets all the corresponding thalamocortical (TC) circuits in motion. Over the last two decades, behavioural, electrophysiological, anatomical and neurochemical findings have been accumulating, supporting the complex nature of the TRN and raising questions about the validity of this speculative hypothesis. Indeed, our knowledge of the actual functioning of the TRN is still sprinkled with unresolved questions. Therefore, the time has come to join forces and discuss some recent cellular and network findings concerning this diencephalic GABAergic structure, which plays important roles during various states of consciousness. On the whole, the present critical survey emphasizes the TRN's complexity, and provides arguments combining anatomy, physiology and cognitive psychology.

Attention↗

PubMed2003

Cellular interactions in the rat somatosensory thalamocortical system during normal and epileptic 5-9 Hz oscillations.

In Genetic Absence Epilepsy Rats from Strasbourg (GAERS), generalized spike-and-wave (SW) discharges (5-9 SW s(-1)) develop during quiet immobile wakefulness from a natural, medium-voltage, 5-9 Hz rhythm. This study examines the spatio-temporal dynamics of cellular interactions in the somatosensory thalamocortical system underlying the generation of normal and epileptic 5-9 Hz oscillations. Paired single-unit and multi-unit recordings between the principal elements of this circuit and intracellular recordings of thalamic, relay and reticular, neurones were conducted in neuroleptanalgesied GAERS and control, non-epileptic, rats. The identity of the recorded neurones was established following juxtacellular or intracellular marking. At least six major findings have emerged from this study. (1) In GAERS, generalized spike-and-wave discharges were correlated with synchronous rhythmic firings in related thalamic relay and reticular neurones. (2) Usually, corticothalamic discharges phase-led related relay and reticular firings. (3) A depolarizing wave emerging from a barrage of EPSPs was the cause of both relay and reticular discharges. (4) In some relay cells, which had a relatively high membrane input resistance, the depolarizing wave had the shape of a ramp, which could trigger a low-threshold Ca2+ spike. (5) In reticular cells, the EPSP barrage could further trigger voltage-dependent depolarizations. (6) The epilepsy-related thalamic, relay and reticular, intracellular activities were similar to the normal-related thalamic activities. Overall, these findings strongly suggest that, during absence seizures, corticothalamic neurones play a primary role in the synchronized excitation of thalamic relay and reticular neurones. The present study further suggests that absence-related spike-and-wave discharges correspond to hypersynchronous wake-related physiological oscillations.

Animals↗