title: Nucleus-specific differences in GABA(A)-receptor-mediated inhibition are enhanced during thalamic development.
abstract: Inhibitory postsynaptic currents (IPSCs) mediated by GABA(A) receptors are much slower in neurons of the thalamic reticular nucleus (RTN) versus those in the ventrobasal complex (VB) of young rats. Here we confirm and extend those findings regarding GABA(A) response heterogeneity especially in relation to development. Whole cell patch-clamp recordings were used to investigate GABA(A) spontaneous and electrically evoked IPSCs (sIPSCs/eIPSCs) in RTN and VB cells of different aged rats. Consistent with earlier findings, sIPSC duration at P8-12 was considerably longer in RTN (weighted decay time constant: tau(D,W) = 56.2 +/- 4.9 ms; mean +/- SE) than in VB (tau(D,W) = 15.8 +/- 1.0 ms) neurons. Decay kinetics in RTN neurons did not differ at P21-30 (45.5 +/- 4.7 ms) or P42-60 (51.6 +/- 10.6 ms). In contrast, VB sIPSCs were significantly faster at both P21-30 (tau(D,W) = 10.8 +/- 0.9 ms) and P42-60 (tau(D,W) = 9.2 +/- 0.4 ms) compared with P8-12 animals. IPSCs displayed differential outward rectification and temperature dependence, providing further support for nucleus-specific responses. tau(D,W) increased with membrane depolarization but with a net larger effect in VB. By contrast, tau(D,W) was always smaller at higher temperatures but with relatively greater difference observed in RTN. Thus nuclear differences in GABA(A) IPSCs are not only maintained, but enhanced in the mature rodent under physiological conditions. These findings support our hypothesis that unique GABA(A) receptors mediate slowly decaying RTN IPSCs that are a critical and enduring feature of the thalamic circuit. This promotes powerful intranuclear inhibition and likely prevents epileptiform thalamocortical hypersynchrony.
authors.affiliation: Department of Neurology, Stanford University Medical Center, Stanford, California 94305-5300, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Huntsman
authors.forename: J R
authors.initials: JR
authors.lastname: Huguenard
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D008297:Male; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*; D012154:Reticular Formation / Q000254:growth & development / Q000502:physiology; D013696:Temperature; D013787:Thalamic Nuclei / Q000254:growth & development / Q000502:physiology*; D013788:Thalamus / Q000254:growth & development / Q000502:physiology*
chemical_list: D011963:Receptors, GABA-A