Role of inhibitory autophosphorylation of calcium/calmodulin-dependent kinase II (αCAMKII) in persistent (>24 h) hippocampal LTP and in LTD facilitated by novel object-place learning and recognition in mice.
Experience-dependent synaptic plasticity is widely expressed in the mammalian brain and is believed to underlie memory formation. Persistent forms of synaptic plasticity in the hippocampus, such as long-term potentiation (LTP) and long-term depression (LTD) are particularly of interest, as evidence is accumulating that they are expressed as a consequence of, or at the very least in association with, hippocampus-dependent novel learning events. Learning-facilitated plasticity describes the property of hippocampal synapses to express persistent synaptic plasticity when novel spatial learning is combined with afferent stimulation that is subthreshold for induction of changes in synaptic strength. In mice it occurs following novel object recognition and novel object-place recognition. Calmodulin-dependent kinase II (CAMKII) is strongly expressed in synapses and has been shown to be required for hippocampal LTP in vitro and for spatial learning in the water maze. Here, we show that in mice that undergo persistent inhibitory autophosphorylation of αCAMKII, object-place learning is intact. Furthermore, these animals demonstrate a higher threshold for induction of persistent (>24 h) hippocampal LTP in the hippocampal CA1 region during unrestrained behaviour. The transgenic mice also express short-term depression in response to afferent stimulation frequencies that are ineffective in controls. Furthermore, they express stronger LTD in response to novel learning of spatial configurations compared to controls. These findings support that modulation of αCAMKII activity via autophosphorylation at the Thr305/306 site comprises a key mechanism for the maintenance of synaptic plasticity within a dynamic range. They also indicate that a functional differentiation occurs in the way spatial information is encoded: whereas LTP is likely to be critically involved in the encoding of space per se, LTD appears to play a special role in the encoding of the content or features of space.
Department of Neurophysiology, Medical Faculty, Ruhr University Bochum, Universitaetsstr. 150, MA 4/150, 44780 Bochum, Germany.
Jinzhong Jeremy
JJ
Goh
Department of Neurophysiology, Medical Faculty, Ruhr University Bochum, Universitaetsstr. 150, MA 4/150, 44780 Bochum, Germany. Electronic address: denise.manahan-vaughan@rub.de.
Denise
D
Manahan-Vaughan
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000201:enzymology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D005071:Evoked Potentials; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009483:Neuropsychological Tests; D010766:Phosphorylation; D021641:Recognition, Psychology / Q000502:physiology*; D065853:Spatial Learning / Q000502:physiology*
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
In vivo; LTD; LTP; Mouse; Murine; Synaptic plasticity