80 the cerebellum climbing fiber impulses imply discrepancy between intended and actual move- ments, and between demand for precision and discontent about inaccurate per- formance (Ito, 2009). However, what mechanisms organize these activities is unclear when climbing fibers and other CRF-containing neurons located in the amygdala and hypothalamus have no obvious neuronal connections. Insulin-like growth factor-1 (IGF-1). This basic peptide is involved in cell growth and differentiation and it operates at diverse synaptic sites. Purkinje cells exhibit IGF-1 immunoreactivity localized in the rough endoplasmic reticulum (Aguado et al., 1992). In the human cerebellum, IGF-1 immunoreactivity is pro- nounced throughout Purkinje cells and their extrusions, and it is also observed in the IO (Aguado et al., 1994). Electrical stimulation of the IO significantly increases the IGF-1 level in the cerebellar cortex. Whether IGF-1 is actually involved in LTD induction is uncertain, but because IGF-1 stimulates DAG production (Kojima et al., 1990), it is possible that DAG, in turn, stimulates PKC, which is required for LTD induction. IGF-1 may be involved in the maintenance of den- dritic spine morphology because an IGF-1 antisense oligonucleotide injected into the IO was shown to induce a significant reduction in the size of the dendritic spines on Purkinje cells. Antisense oligonucleotide was also shown to evoke a sig- nificant and reversible decrease in IGF-1 level in the contralateral cerebellum (Nieto-Bona et al., 1997). Brain-derived neurotrophic factor (BDNF). Evidence is scarce regarding the involvement of this factor in conjunctive LTD induction. Nevertheless, when quisqualate application induces LTD, a significant increase in the level of BDNF's mRNA expression occurs in cerebellar tissues, with a peak 4 hours after the appli- cation (Yuzaki et al., 1994). Even though the major source of this expression level increase is its granule cell fraction, the Purkinje cell fraction also contains BDNF's mRNA. If BDNF is co-induced with LTD, it might play a role in the later phases of LTD. 7-5 Summary The basic properties and underlying signal transduction of conjunctive LTD have been analyzed in great detail. The complexity of this signal transduction should be a safeguard for its robust operation under variable conditions. The possibility that conjunctive LTD plays a crucial role in motor learning is examined in later chap- ters. The pharmacological and genetic tools required for analyzing such roles are now becoming available.