Long-term potentiation in the hippocampal CA1 area and dentate gyrus plays different roles in spatial learning.
NMDA receptor-dependent long-term potentiation (LTP) at hippocampal synapses has been considered a crucial component of the cellular basis for learning and memory. This form of LTP occurs in excitatory synapses in both the CA1 area and the dentate gyrus in the hippocampus. However, differential roles of LTP in these areas have not yet been identified. To address this issue, we enhanced the degree of LTP by expressing Ca2+-permeable AMPA receptors at either hippocampal CA1 or dentate gyrus synapses using Sindbis viral vectors (SINs) encoding both green fluorescent proteins and unedited GluR2 (GluR2Q) subunits, and examined their effects on rat spatial learning. The viral vectors were locally injected into the 8-week-old-rat brain in vivo bilaterally. The postsynaptic expression of Ca2+-permeable AMPA receptors enhanced the degree of LTP, and induced NMDA receptor-independent LTP in the presence of the NMDA receptor antagonist in SIN-infected regions in both CA1 and dentate gyrus in hippocampal slice preparations. However, the regional expression of Ca2+-permeable AMPA receptors caused opposite behavioural consequences on the Morris water maze task: rats with SIN-infected CA1 pyramidal cells showed shorter escape latency and better probe test performance, whereas those with SIN-infected dentate gyrus granule cells showed impaired performance. Thus, it was demonstrated that CA1 and dentate gyrus synapses play different functional roles in spatial learning despite their similar mechanism for LTP induction.
Okada
Takashi
T
Department of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8519, Japan. okada@psy.senshu-u.ac.jp
Yamada
Nobuaki
N
Tsuzuki
Keisuke
K
Horikawa
Hiroshi P M
HP
Tanaka
Kohichi
K
Ozawa
Seiji
S
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D018891:Dentate Gyrus / Q000502:physiology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D005822:Genetic Vectors / Q000008:administration & dosage; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000502:physiology*; D007276:Injections, Intraventricular; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008164:Luminescent Proteins; D018782:Maze Learning / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010957:Plasmids; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D012845:Sindbis Virus / Q000235:genetics; D013569:Synapses / Q000378:metabolism*
D008164:Luminescent Proteins; D018091:Receptors, AMPA; D049452:Green Fluorescent Proteins; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium