Regional differences in hippocampal calcium handling provide a cellular mechanism for limiting plasticity.
Although much is known about the mechanisms underlying synaptic plasticity, the cellular mechanisms that negatively regulate plasticity in some brain regions are considerably less studied. One region where neurons do not reliably express long-term potentiation (LTP) is the CA2 subfield of the hippocampus. Given the connection between synaptic plasticity and increases in postsynaptic [Ca(2+)], and that CA2 neurons express a large number of calcium-regulating proteins, we tested the hypothesis that the relative lack of LTP in CA2 results from differences in the calcium dynamics of these neurons. By measuring calcium-dependent fluorescence transients in dendritic spines, we show that CA2 neurons have smaller action potential-evoked intracellular Ca(2+) transients because of a higher endogenous Ca(2+)-buffering capacity and significantly higher rates of Ca(2+) extrusion when compared with CA1 and CA3 neurons. Perfusion with higher external [Ca(2+)] during induction restores LTP to CA2 neurons, suggesting that they possess the cellular machinery required for plasticity, but that the restriction of postsynaptic [Ca(2+)] limits its expression. Camstatin, an analogue of the calcium-modulating protein Pep-19 strongly expressed in CA2 neurons, blocked LTP and increased Ca(2+) extrusion in CA1 neurons, suggesting a role for extrusion in the regulation of plasticity in CA2. In agreement with this idea, we found that intracellular introduction of a PMCA pump inhibitor (carboxyeosin) allows for the induction of LTP in CA2 neurons. Our results indicate that regulation of postsynaptic [Ca(2+)] through modulation of extrusion and/or buffering regulates expression of LTP in CA2 and potentially other brain regions.
Simons
Stephen B
SB
Laboratory of Neurobiology, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Escobedo
Yasmin
Y
Yasuda
Ryohei
R
Dudek
Serena M
SM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D003712:Dendrites / Q000378:metabolism; D004594:Electrophysiology / Q000379:methods; D004801:Eosine Yellowish-(YS) / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007700:Kinetics; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D051381:Rats; D009435:Synaptic Transmission
D002118:Calcium; D004801:Eosine Yellowish-(YS)