Biomedical subjects

Rostislav Turecek

Publications and source records attributed to Rostislav Turecek.

4 recordsLinked to original sources

PubMed2006

Differential compartmentalization and distinct functions of GABAB receptor variants.

GABAB receptors are the G protein-coupled receptors for the main inhibitory neurotransmitter in the brain, gamma-aminobutyric acid (GABA). Molecular diversity in the GABAB system arises from the GABAB1a and GABAB1b subunit isoforms that solely differ in their ectodomains by a pair of sushi repeats that is unique to GABAB1a. Using a combined genetic, physiological, and morphological approach, we now demonstrate that GABAB1 isoforms localize to distinct synaptic sites and convey separate functions in vivo. At hippocampal CA3-to-CA1 synapses, GABAB1a assembles heteroreceptors inhibiting glutamate release, while predominantly GABAB1b mediates postsynaptic inhibition. Electron microscopy reveals a synaptic distribution of GABAB1 isoforms that agrees with the observed functional differences. Transfected CA3 neurons selectively express GABAB1a in distal axons, suggesting that the sushi repeats, a conserved protein interaction motif, specify heteroreceptor localization. The constitutive absence of GABAB1a but not GABAB1b results in impaired synaptic plasticity and hippocampus-dependent memory, emphasizing molecular differences in synaptic GABAB functions.

Animals↗

PubMed2004

Staggered development of GABAergic and glycinergic transmission in the MNTB.

Maturation of some brain stem and spinal inhibitory systems is characterized by a shift from GABAergic to glycinergic transmission. Little is known about how this transition is expressed in terms of individual axonal inputs and synaptic sites. We have explored this issue in the rat medial nucleus of the trapezoid body (MNTB). Synaptic responses at postnatal days 5-7 (P5-P7) were small, slow, and primarily mediated by GABA(A) receptors. By P8-P12, an additional, faster glycinergic component emerged. At these ages, GABA(A), glycine, or both types of receptors mediated transmission, even at single synaptic sites. Thereafter, glycinergic development greatly accelerated. By P25, evoked inhibitory postsynaptic currents (IPSCs) were 10 times briefer and 100 times larger than those measured in the youngest group, suggesting a proliferation of synaptic inputs activating fast-kinetic receptors. Glycinergic miniature IPSCs (mIPSCs) increased markedly in size and decay rate with age. GABAergic mIPSCs also accelerated, but declined slightly in amplitude. Overall, the efficacy of GABAergic inputs showed little maturation between P5 and P20. Although gramicidin perforated-patch recordings revealed that GABA or glycine depolarized P5-P7 cells but hyperpolarized P14-P15 cells, the young depolarizing inputs were not suprathreshold. In addition, vesicle-release properties of inhibitory axons also matured: GABAergic responses in immature rats were highly asynchronous, while in older rats, precise, phasic glycinergic IPSCs could transmit even with 500-Hz stimuli. Thus development of inhibition is characterized by coordinated modifications to transmitter systems, vesicle release kinetics, Cl- gradients, receptor properties, and numbers of synaptic inputs. The apparent switch in GABA/glycine transmission was predominantly due to enhanced glycinergic function.

Age Factors↗

PubMed2004

Inhibitory control at a synaptic relay.

The mammalian medial nucleus of the trapezoid body (MNTB) harbors one of the most powerful terminals in the CNS, the calyx of Held. The mechanisms known to regulate this synaptic relay are relatively ineffective. Here, we report the presence of a remarkably robust and fast-acting glycinergic inhibitory system capable of suppressing calyceal transmission. Evoked glycinergic IPSCs were relatively small in 2-week-old rats, an age by which calyceal maturation has reportedly neared completion. However, by postnatal day 25 (P25), glycinergic transmission had undergone a vigorous transformation, resulting in peak synaptic conductances as high as 280 nS. These are comparable with glutamatergic conductances activated by calyceal inputs. Decay kinetics for IPSCs were severalfold faster than for glycinergic synaptic events reported previously. At physiological temperatures in P25 rats, IPSCs decayed in approximately 1 msec and could be elicited at frequencies up to 500 Hz. Moreover, EPSPs triggered by glutamatergic signals derived from the calyx or simulated by conductance clamp were suppressed when preceded by simulated glycinergic IPSPs. The matching of excitatory transmission in the calyx of Held by a powerful, precision inhibitory system suggests that the relay function of the MNTB may be rapidly modified during sound localization.

Animals↗

PubMed2002

Reciprocal developmental regulation of presynaptic ionotropic receptors.

Activation of ionotropic glycine receptors potentiates glutamate release in mature calyceal nerve terminals of the rat medial nucleus of the trapezoid body, an auditory brainstem nucleus. In young rats, glycine and its receptors are poorly expressed. We therefore asked whether GABA (gamma-aminobutyric acid) might play a larger role than glycine in the regulation of glutamate release in the absence of glycine receptors. Indeed, in rats younger than postnatal day 11 (P11), and before the onset of hearing, calyces expressed high levels of ionotropic GABA(A) receptors but few glycine receptors. Isoguvacine, a selective agonist at GABA(A) receptors, strongly enhanced excitatory postsynaptic currents in young rats but had little effect in rats older than P11. Down-regulation of presynaptic GABA(A) receptors did not reflect global changes in receptor expression, because the magnitude of GABA and glycine responses was similar at P13 in the parent-cell bodies of the calyces, the bushy cells of the cochlear nucleus. In outside-out patches excised from the nonsynaptic face of calyces, GABA and glycine evoked single-channel currents consistent with the properties of postsynaptic GABA(A) and glycine receptors. Inhibitory GABA(B) receptors were present on the calyx at all developmental stages examined. Thus, GABA initially acts on two receptor subtypes, both promoting and inhibiting glutamate release. With age, the former role is transferred to the glycine receptor during the period in which postsynaptic glycinergic transmission is acquired.

Animals↗