title: Long-term effects of 3-acetylpyridine-induced destruction of cerebellar climbing fibers on Purkinje cell inhibition of vestibulospinal tract cells of the rat.
abstract: The inhibitory action of Purkinje cells on vestibulospinal tract (VST) cells was examined in rats deprived of climbing fibers with 3-acetylpyridine (3-AP) intoxication. In order to resolve discrepancies raised in previous studies with various means, special efforts were devoted to directly estimate Purkinje cell inhibition at synaptic levels by using intracellular recording, to avoid sampling bias by using a systematic survey of VST cells in each rat, and to evaluate the time-dependence of the effects of climbing fiber deafferentation by regular testing at 10 day intervals until 160 days after 3-AP intoxication. As compared with 661 VST cells impaled in 15 control rats, 1771 VST neurons impaled in 29 3-AP-treated rats revealed four basic changes in the monosynaptic inhibitory postsynaptic potentials (IPSPs) induced by stimulation of Purkinje cell axons in the white matter of the cerebellar anterior lobe. First, the rate of IPSP occurrence among VST cells was 0.64 in control rats; at more than 10 days after 3-AP intoxication it decreased gradually, down to 0.37-0.38 at the 70th-81st days, and thereafter increased up to 0.53 by the 160th day. The rate of IPSP occurrence varied considerably between the rostral and caudal regions, and also between the dorsal and ventral divisions of the VST cell population, but its reduction after 3-AP intoxication occurred approximately in parallel in all divisions. Second, IPSPs evoked with standard 500 microA pulse stimuli were smaller in size on and after day 10. The reduction of IPSP size was by as much as 53% of control values at the 70th-101st days in the dorsal division, but no significant change occurred in the ventral division of the VST cell population. Third, the latency of the IPSPs was prolonged by about 0.25 ms on and after day 10. Analysis of the relationship between the IPSP latency and the dorsoventral location of VST cells in the medulla suggests that the major cause for the prolongation of IPSP latency is an increased synaptic delay at Purkinje cell axon terminals. Fourth, the cerebellar stimulation threshold for evoking IPSPs was almost always below 100 microA in control rats, but values of 100-250 microA were common after the 40th day. Thus, climbing fiber deafferentation exerts long-term influences on excitability of Purkinje cell axons, and on the connectivity and synaptic transmission from Purkinje cell axons to VST cells.
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D008564:Membrane Potentials; D009433:Neural Inhibition; D009434:Neural Pathways / Q000502:physiology; D011689:Purkinje Cells / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology*; D014726:Vestibular Nuclei / Q000502:physiology*
chemical_list: D011725:Pyridines; C010835:3-acetylpyridine