Glycinergic synaptic currents in the deep cerebellar nuclei.
Despite evidence of local glycinergic circuits in the mature cerebellar nuclei the result of their activation remains unknown. Here, using whole cell recordings in rat cerebellar slices we demonstrated that after postnatal day 17 (>P17) glycinergic IPSCs can be readily evoked in large deep cerebellar nuclear neurons (DCNs), in the same way as in neonatal DCNs (P7-P10). Spontaneous glycinergic IPSCs were very rare but direct presynaptic depolarization by superfusion with elevated potassium concentration or application of 4-aminopyridine consistently evoked strychnine sensitive IPSCs. Glycinergic IPSCs showed fast kinetics in >P17 DCNs while were significantly slower in neonatal DCNs. Immuno-histochemical investigations using a specific marker for glycinergic fibers and terminals showed low density of immuno-fluorescent puncta, putative glycinergic boutons surrounding P18-P23 DCNs, in agreement with the rare spontaneous synaptic activity. But putative glycinergic boutons were present in critical areas for the control of spike generation. In contrast to adult and neonatal DCNs, glycinergic IPSCs could not be induced in juvenile DCNs (P13-P17) despite similar perisomatic immuno-staining pattern and expression of glycinergic receptors to >P17 DCNs. The latter results demonstrate substantial postnatal development of glycinergic cerebellar nuclei circuits. The cerebellum is involved in rapidly controlling ongoing movements. For that function, it is thought important the temporal and spatial precision of its output, which is carried to target structures by DCNs. The present study, by demonstrating fast glycinergic IPSCs in mature DCNs, points to the activation of glycinergic microcircuits as one of the possible mechanism involved in the spatio-temporal control of cerebellar output.
Pedroarena
Christine M
CM
Department of Cognitive Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Otfried Müller Strasse 27, 72076 Tübingen, Germany. christine.pedroarena@uni-tuebingen.de
Kamphausen
Susanne
S
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002529:Cerebellar Nuclei / Q000166:cytology* / Q000502:physiology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism*; D018684:Glycine Agents / Q000494:pharmacology; D050487:Glycine Plasma Membrane Transport Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D007736:Kynurenic Acid / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013331:Strychnine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018684:Glycine Agents; D050487:Glycine Plasma Membrane Transport Proteins; D011724:Pyridazines; C017069:bicuculline methiodide; C049853:gabazine; D007736:Kynurenic Acid; D013331:Strychnine; D005998:Glycine; D001640:Bicuculline