Extensive immunolesions of basal forebrain cholinergic system impair offspring recognition in sheep

Neuroscience. 2001;106(1):103-16. doi: 10.1016/s0306-4522(01)00265-2.


The involvement of the basal forebrain cholinergic system has been extensively investigated in instrumental learning but little is known of its participation in social memory, especially in the memorization of individual traits of a conspecific. The present study tested in sheep its contribution to both instrumental learning and individual offspring recognition. Six weeks before parturition, ewes received injections of a specific cholinergic immunotoxin (ME20.4 IgG-saporin) into the lateral ventricles (150 microg) and in some cases additional immunotoxin injections into the nucleus basalis (11 microg/side). After 3 weeks of recovery, ewes were trained on a classical instrumental visual discrimination task known to be sensitive to cholinergic deficits. The formation of memory of offspring was assessed through both olfactory and visual/auditory recognition tasks. Olfactory recognition was tested by presenting at suckling successively an alien and the familiar lamb at 2 and 4 h after parturition. Visual/auditory recognition of the lamb was performed using a non-olfactory discrimination test between the familiar and an alien lamb after 12 h of mother-young contact. The lesion extent was assessed by counting choline acetyltransferase-immunopositive neurons in the basal forebrain and measuring the density of acetylcholinesterase fibers in different target areas. Results showed that immunotoxic lesions delayed acquisition of the instrumental visual discrimination. Moreover, olfactory recognition of the lamb was severely impaired while visual/auditory lamb recognition was marginally altered. There was no evidence for sensorimotor or motivational deficits. Importantly, impairment was observed in animals for which loss of basal forebrain cholinergic neurons and their efferent fibers was higher than 75%, while striatal cholinergic neurons and Purkinje cells were unaffected. This study provides evidence that the basal forebrain cholinergic system contributes not only to instrumental but also to social learning. In addition, the cholinergic modulation seems of importance for processing visual and olfactory modalities. However, since only extensive lesions affect performance, this indicates that the basal forebrain cholinergic system possesses substantial reserve capacity to sustain cognitive functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Animals, Suckling / physiology
  • Antibodies, Monoclonal
  • Auditory Perception / drug effects
  • Auditory Perception / physiology
  • Basal Nucleus of Meynert / drug effects
  • Basal Nucleus of Meynert / pathology
  • Basal Nucleus of Meynert / physiopathology*
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Body Temperature / drug effects
  • Body Temperature / physiology
  • Body Weight / drug effects
  • Body Weight / physiology
  • Choline O-Acetyltransferase / metabolism
  • Cholinergic Agents / pharmacology
  • Cholinergic Fibers / drug effects
  • Cholinergic Fibers / metabolism*
  • Cholinergic Fibers / pathology
  • Denervation
  • Discrimination Learning / drug effects
  • Discrimination Learning / physiology
  • Female
  • Immunohistochemistry
  • Immunotoxins / pharmacology
  • Maternal Behavior / drug effects
  • Maternal Behavior / physiology*
  • Memory / drug effects
  • Memory / physiology*
  • Memory Disorders / chemically induced
  • Memory Disorders / pathology
  • Memory Disorders / physiopathology*
  • Models, Animal
  • N-Glycosyl Hydrolases
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Neurons / drug effects
  • Neurons / metabolism
  • Pattern Recognition, Visual / drug effects
  • Pattern Recognition, Visual / physiology*
  • Ribosome Inactivating Proteins, Type 1
  • Saporins
  • Sheep
  • Smell / drug effects
  • Smell / physiology*


  • Antibodies, Monoclonal
  • Cholinergic Agents
  • Immunotoxins
  • ME20.4 IgG-saporin
  • Ribosome Inactivating Proteins, Type 1
  • Choline O-Acetyltransferase
  • N-Glycosyl Hydrolases
  • Saporins
  • Acetylcholine