TY - JOUR
T1 - Dynamic GABAA receptor subtype-specific modulation of the synchrony and duration of thalamic oscillations
AU - Sohal, Vikaas S.
AU - Keist, Ruth
AU - Rudolph, Uwe
AU - Huguenard, John R.
PY - 2003/5/1
Y1 - 2003/5/1
N2 - Networks of interconnected inhibitory neurons, such as the thalamic reticular nucleus (TRN), often regulate neural oscillations. Thalamic circuits generate sleep spindles and may contribute to some forms of generalized absence epilepsy, yet the exact role of inhibitory connections within the TRN remains controversial. Here, by using mutant mice in which the thalamic effects of the anti-absence drug clonazepam (CZP) are restricted to either relay or reticular nuclei, we show that the enhancement of intra-TRN inhibition is both necessary and sufficient for CZP to suppress evoked oscillations in thalamic slices. Extracellular and intracellular recordings show that CZP specifically suppresses spikes that occur during bursts of synchronous firing, and this suppression grows over the course of an oscillation, ultimately shortening that oscillation. These results not only identify a particular anatomical and molecular target for anti-absence drug design, but also elucidate a specific dynamic mechanism by which inhibitory networks control neural oscillations.
AB - Networks of interconnected inhibitory neurons, such as the thalamic reticular nucleus (TRN), often regulate neural oscillations. Thalamic circuits generate sleep spindles and may contribute to some forms of generalized absence epilepsy, yet the exact role of inhibitory connections within the TRN remains controversial. Here, by using mutant mice in which the thalamic effects of the anti-absence drug clonazepam (CZP) are restricted to either relay or reticular nuclei, we show that the enhancement of intra-TRN inhibition is both necessary and sufficient for CZP to suppress evoked oscillations in thalamic slices. Extracellular and intracellular recordings show that CZP specifically suppresses spikes that occur during bursts of synchronous firing, and this suppression grows over the course of an oscillation, ultimately shortening that oscillation. These results not only identify a particular anatomical and molecular target for anti-absence drug design, but also elucidate a specific dynamic mechanism by which inhibitory networks control neural oscillations.
KW - Benzodiazepines
KW - Generalized absence epilepsy
KW - Inhibition
KW - Interneuronal network
KW - Spike wave discharge
KW - Thalamus
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U2 - 10.1523/jneurosci.23-09-03649.2003
DO - 10.1523/jneurosci.23-09-03649.2003
M3 - Article
C2 - 12736336
AN - SCOPUS:0038206590
VL - 23
SP - 3649
EP - 3657
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 9
ER -