title: Intracerebellar infusion of the protein kinase M zeta (PKMζ) inhibitor zeta-inhibitory peptide (ZIP) disrupts eyeblink classical conditioning.
abstract: Protein kinase M zeta (PKM-ζ), a constitutively active N-terminal truncated form of PKC-ζ, has long been implicated in a cellular correlate of learning, long-term potentiation (LTP). Inhibition of PKM-ζ with zeta-inhibitory peptide (ZIP) has been shown in many brain structures to disrupt maintenance of AMPA receptors, irreversibly disrupting numerous forms of learning and memory that have been maintained for weeks. Delay eyeblink conditioning (EBC) is an established model for the assessment of cerebellar learning; here, we show that PKC-ζ and PKM-ζ are highly expressed in the cerebellar cortex, with highest expression found in Purkinje cell (PC) nuclei. Despite being highly expressed in the cerebellar cortex, no studies have examined how regulation of cerebellar PKM-ζ may affect cerebellar-dependent learning and memory. Given its disruption of learning in other brain structures, we hypothesized that ZIP would also disrupt delay EBC. We have shown that infusion of ZIP into the lobulus simplex of the rat cerebellar cortex can indeed significantly disrupt delay EBC. (PsycINFO Database Record
authors.affiliation: Neuroscience Graduate Program.
authors.forename: Kutibh
authors.initials: K
authors.lastname: Chihabi
authors.affiliation: Department of Pharmacology.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Morielli
authors.affiliation: Department of Psychological Science.
authors.forename: John T
authors.initials: JT
authors.lastname: Green
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002531:Cerebellum; D003214:Conditioning, Classical / Q000502:physiology*; D003215:Conditioning, Eyelid / Q000502:physiology*; D007150:Immunohistochemistry; D007858:Learning; D008297:Male; D008568:Memory / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D011689:Purkinje Cells; D051381:Rats; D017208:Rats, Wistar
chemical_list: D011493:Protein Kinase C