title: Functional disconnection of the substantia nigra pars compacta from the pedunculopontine nucleus impairs learning of a conditioned avoidance task.
abstract: The pedunculopontine tegmental nucleus (PPTg) targets nuclei in the basal ganglia, including the substantia nigra pars compacta (SNc), in which neuronal loss occurs in Parkinson's disease, a condition in which patients show cognitive as well as motor disturbances. Partial loss and functional abnormalities of neurons in the PPTg are also associated with Parkinson's disease. We hypothesized that the interaction of PPTg and SNc might be important for cognitive impairments and so investigated whether disrupting the connections between the PPTg and SNc impaired learning of a conditioned avoidance response (CAR) by male Wistar rats. The following groups were tested: PPTg unilateral; SNc unilateral; PPTg-SNc ipsilateral (ipsilateral lesions in PPTg and SNc); PPTg-SNc contralateral (contralateral lesions in PPTg and SNc); sham lesions (of each type). SNc lesions were made with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine HCl (MPTP, 0.6micromol); PPTg lesions with ibotenate (24nmol). After recovery, all rats underwent 50-trial sessions of 2-way active avoidance conditioning for 3 consecutive days. Rats with unilateral lesions in PPTg or SNc learnt this, however rats with contralateral (but not ipsilateral) combined lesions in both structures presented no sign of learning. This effect was not likely to be due to sensorimotor impairment because lesions did not affect reaction time to the tone or footshock during conditioning. However, an increased number of non-responses were observed in the rats with contralateral lesions. The results support the hypothesis that a functional interaction between PPTg and SNc is needed for CAR learning and performance.
authors.affiliation: Laboratorio de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Parana (UFPR), C.P. 19031, 81531-980 Curitiba, Brazil.
authors.forename: Mariza
authors.initials: M
authors.lastname: Bortolanza
authors.forename: Evellyn C
authors.initials: EC
authors.lastname: Wietzikoski
authors.forename: Suelen L
authors.initials: SL
authors.lastname: Boschen
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Dombrowski
authors.forename: Mary
authors.initials: M
authors.lastname: Latimer
authors.forename: Duncan A A
authors.initials: DA
authors.lastname: Maclaren
authors.forename: Philip
authors.initials: P
authors.lastname: Winn
authors.forename: Claudio
authors.initials: C
authors.lastname: Da Cunha
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology; D007051:Ibotenic Acid / Q000494:pharmacology; D008297:Male; D009434:Neural Pathways / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D045042:Pedunculopontine Tegmental Nucleus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology; D013378:Substantia Nigra / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D009498:Neurotoxins; D007051:Ibotenic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine