TY - JOUR
T1 - Impairment of eyeblink conditioning in GluRδ2-mutant mice depends on the temporal overlap between conditioned and unconditioned stimuli
AU - Kishimoto, Yasushi
AU - Kawahara, Shigenori
AU - Fujimichi, Ryoko
AU - Mori, Hisashi
AU - Mishina, Masayoshi
AU - Kirino, Yutaka
PY - 2001
Y1 - 2001
N2 - Mice lacking the glutamate receptor subunit δ2 (GluRδ2) are deficient in cerebellar long-term depression (LTD) at the parallel fibre-Purkinje cell synapses. We conducted delay and trace eyeblink conditioning with these mice, using various temporal intervals between the conditioned stimulus (CS) and unconditioned stimulus (US). During trace conditioning in which a stimulus-free trace interval (TI) of 250, 100 or 50 ms intervened between the 352-ms tone CS and 100-ms US, GluRδ2-mutant mice learned as successfully as wild-type mice. Even in the paradigm with TI = 0 ms, in which the end of CS and onset of US are simultaneous, there was no difference between the GluRδ2-mutant and wild-type mice in their acquisition of a conditioned response. However, in the delay paradigm in which the 452-ms CS overlapped temporally with the coterminating 100-ms US, GluRδ2-mutant mice exhibited severe learning impairment. The present study together with our previous work [Kishimoto, Y., Kawahara, S., Suzuki, M., Mori, H., Mishina, M. & Kirino, Y. (2001) Eur. J. Neurosci., 13, 1249-1254], indicates that cerebellar LTD-independent learning is possible in paradigms without temporal overlap between the CS and US. On the other hand, GluRδ2 and cerebellar LTD are essential for learning when there is CS-US temporal overlap, suggesting that the cerebellar neural substrates underlying eyeblink conditioning may change, depending on the temporal overlap of the CS and US.
AB - Mice lacking the glutamate receptor subunit δ2 (GluRδ2) are deficient in cerebellar long-term depression (LTD) at the parallel fibre-Purkinje cell synapses. We conducted delay and trace eyeblink conditioning with these mice, using various temporal intervals between the conditioned stimulus (CS) and unconditioned stimulus (US). During trace conditioning in which a stimulus-free trace interval (TI) of 250, 100 or 50 ms intervened between the 352-ms tone CS and 100-ms US, GluRδ2-mutant mice learned as successfully as wild-type mice. Even in the paradigm with TI = 0 ms, in which the end of CS and onset of US are simultaneous, there was no difference between the GluRδ2-mutant and wild-type mice in their acquisition of a conditioned response. However, in the delay paradigm in which the 452-ms CS overlapped temporally with the coterminating 100-ms US, GluRδ2-mutant mice exhibited severe learning impairment. The present study together with our previous work [Kishimoto, Y., Kawahara, S., Suzuki, M., Mori, H., Mishina, M. & Kirino, Y. (2001) Eur. J. Neurosci., 13, 1249-1254], indicates that cerebellar LTD-independent learning is possible in paradigms without temporal overlap between the CS and US. On the other hand, GluRδ2 and cerebellar LTD are essential for learning when there is CS-US temporal overlap, suggesting that the cerebellar neural substrates underlying eyeblink conditioning may change, depending on the temporal overlap of the CS and US.
KW - Associative learning
KW - Cerebellar LTD
KW - Motor learning
KW - Purkinje cell
UR - http://www.scopus.com/inward/record.url?scp=0035783468&partnerID=8YFLogxK
U2 - 10.1046/j.0953-816X.2001.01772.x
DO - 10.1046/j.0953-816X.2001.01772.x
M3 - 学術論文
C2 - 11722613
AN - SCOPUS:0035783468
SN - 0953-816X
VL - 14
SP - 1515
EP - 1521
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 9
ER -