title: Effects of unilateral removal of basal forebrain cholinergic neurons on cued target detection in rats.
abstract: Corticopetal cholinergic neurons in the basal forebrain (BF) were removed unilaterally from rats by infusing the cholinergic immunotoxin 192 IgG-saporin into the substantia innominata. After 2 weeks, the rats with right-hemisphere infusions showed signs of visuospatial neglect for targets in the left visual field in a cued visual target detection task based upon human covert orienting procedures. No behavioral effects were evident 4-6 weeks post-infusion. Ten to 22 weeks post-infusion all rats responded more quickly and less accurately to targets in the visual field contralateral to the infusion than to targets ipsilateral to the infusion: further, accuracy for contralateral targets decreased with increasing time between trial initiation and target presentation (target delay), whereas accuracy for ipsilateral targets increased with target delay. Cues did not affect responding to targets in the contralateral visual field more than to targets in the ipsilateral field. The changes in performance could not be attributed to sensory or mnemonic impairment or to response bias. The temporal characteristics of response accuracy and latency suggest the competitive interaction of two time-dependent processes: an attentional process which relies upon cholinergic input from the BF, and a response preparation process which is normally inhibited by the attentional process. These results suggest a role for corticopetal cholinergic pathways in maintaining attention to salient stimuli by inhibiting subcortical motor circuits.
authors.affiliation: Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. bushnell.philip@epamail.epa.gov
authors.forename: P J
authors.initials: PJ
authors.lastname: Bushnell
authors.forename: A A
authors.initials: AA
authors.lastname: Chiba
authors.forename: W M
authors.initials: WM
authors.lastname: Oshiro
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D003216:Conditioning, Operant / Q000502:physiology; D003463:Cues; D007839:Functional Laterality; D006651:Histocytochemistry; D000922:Immunotoxins / Q000494:pharmacology; D008297:Male; D009699:N-Glycosyl Hydrolases; D009474:Neurons / Q000502:physiology*; D009949:Orientation / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D016548:Prosencephalon / Q000166:cytology / Q000502:physiology*; D051381:Rats; D012054:Reinforcement, Psychology; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D014796:Visual Perception / Q000502:physiology*
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins