title: Differential alterations of synaptic plasticity in dentate gyrus and CA1 hippocampal area of Calbindin-D28K knockout mice.
abstract: Regulation of the intracellular calcium concentration ([Ca(2+)](i)) is of critical importance for synaptic function. Therefore, neurons buffer [Ca(2+)](i) using intracellular Ca(2+)-binding proteins (CaBPs). Previous evidence suggests that Calbindin-D(28K) (CB), an abundantly expressed endogenous fast CaBP, plays an important role in neuronal survival, motor coordination, spatial learning paradigms and some forms of synaptic plasticity. In the present study, the role of CB in synaptic transmission and plasticity was further investigated using extracellular recordings of synaptic activity in cell- and dendritic layers of dentate gyrus (DG) and CA1 area in hippocampal slices from wild-type, heterozygous and homozygous CB knockout mice. The results demonstrate a consistent failure to maintain long-term potentiation (LTP) in hippocampal DG and CA1 area of knockout mice. Compared to wild-type mice, the paired-pulse ratio of EPSPs recorded in DG is significantly lower in slices from knockout mice, whereas it is significantly higher in CA1 area. The amplitude of the population spike recorded in CA1 area of wild-type mice steadily increases following tetanic stimulation, whereas it steadily decreases in knockout mice. The combined results demonstrate that the absence of CB results in an impairment of LTP maintenance in both hippocampal DG and CA1 area, whereas paired-pulse facilitation and cellular excitability in CA1 area are differentially affected. These results support the role of CB as a critical determinant for several forms of synaptic plasticity in hippocampal DG and CA1 area. It is hypothesized that CB functions as a postsynaptic Ca(2+) buffer as well as a presynaptic Ca(2+) sensor.
authors.affiliation: Neurotoxicology Research Group, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands. r.westerink@uu.nl
authors.forename: R H S
authors.initials: RH
authors.lastname: Westerink
authors.forename: J P
authors.initials: JP
authors.lastname: Beekwilder
authors.forename: W J
authors.initials: WJ
authors.lastname: Wadman
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D064092:Calbindin 1; D064026:Calbindins; D018891:Dentate Gyrus / Q000502:physiology*; D004558:Electric Stimulation; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D064030:S100 Calcium Binding Protein G / Q000235:genetics*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D064030:S100 Calcium Binding Protein G