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  • 1
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The macaque inferotemporal cortex, which is involved in encoding and retrieval of visual long-term memory, consists of two distinct but mutually interconnected areas: area TE (TE) and area 36 (A36). In the present study, we compared delay-period activities of the two subdivisions in terms of their signal contents. We recorded single-unit activities from TE and A36 during a delayed pair association task, in which monkeys were required to choose the paired associate of a cue stimulus after a delay period. The stimulus-selective delay-period activities of single neurons were characterized by using partial correlation coefficients of delay-period activities for each cue stimulus with the cue-period responses to that stimulus (cue-holding index, CHI) and with the cue-period responses to its paired associate (pair-recall index, PRI). The delay-period activities of TE neurons preferentially represented the paired associate (PRI, median = 0.54) rather than the cue stimulus itself (CHI, 0.23) (P 〈 0.001, n = 70), while the delay-period activities of A36 neurons retained both the cue stimulus and its paired associate equivalently (CHI, 0.44; PRI, 0.46) (P = 0.78, n = 38). These results indicate that the signal contents of delay-period activities differ between the two subdivisions: TE mostly represents a sought target that is retrieved from long-term memory, while A36 in addition retains cue-stimulus that is transmitted from earlier visual areas.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In metabotropic glutamate receptor-subtype 1 (mGluR1)-null (mGluR1–/–) mice, cerebellar long-term depression (LTD) and several forms of memory are impaired. However, because mGluR1 is expressed in various brain regions in wild-type mice, it has been difficult to identify which type of memory depends on mGluR1 expressed in a given brain region. Furthermore, severe ataxia in mGluR1–/– mice complicated interpretation of the data from non-cerebellum-dependent tasks. We have generated mGluR1-rescue mice, which express mGluR1 only in Purkinje cells (PCs) of their cerebellum, by introducing the mGluR1α transgene into mGluR1–/– mice under the control of a PC-specific promoter. The mGluR1-rescue mouse has normal LTD and displays no apparent ataxia. Therefore, this mouse is the first animal model in which effects of mGluR1 deficiency outside PCs can be studied without cerebellar dysfunction. We used three eyeblink conditioning paradigms with different temporal specificities between conditioned stimulus (CS) and unconditioned stimulus (US). Delay conditioning, in which CS and US coterminate, was impaired in mGluR1–/– mice but normal in mGluR1-rescue mice. However, both strains of mice displayed severe impairment in trace conditionings, in which a stimulus-free interval of 250 or 500 ms intervened between CS and US. We also examined social transmission of food-preference and novel-object-recognition memory tests. In these tasks, mGluR1-rescue mice showed normal short-term but impaired long-term memory. We conclude that mGluR1 in PCs is indispensable for normal learning of association of temporally contiguous stimuli in associative conditioning. In contrast, mGluR1 in other cell types is required for associating discontiguous stimuli and long-term memory formation in nonspatial hippocampus-dependent learning.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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