A cholinergic mechanism underlies persistent neural activity necessary for eye fixation

Prog Brain Res. 2006:154:211-24. doi: 10.1016/S0079-6123(06)54011-7.


It is generally accepted that the prepositus hypoglossi (PH) nucleus is the site where horizontal eye-velocity signals are integrated into eye-position ones. However, how does this neural structure produce the sustained activity necessary for eye fixation? The generation of the neural activity responsible for eye-position signals has been studied here using both in vivo and in vitro preparations. Rat sagittal brainstem slices including the PH nucleus and the paramedian pontine reticular formation (PPRF) rostral to the abducens nucleus were used for recording intracellularly the synaptic activation of PH neurons from the PPRF. Single electrical pulses applied to the PPRF showed a monosynaptic projection on PH neurons. This synapse was found to be glutamatergic in nature, acting on alpha-amino-3-hydroxy-5-methylisoxazole propionate (AMPA)/kainate receptors. Train stimulation (100 ms, 50-200 Hz) of the PPRF evoked a depolarization of PH neurons, exceeding (by hundreds of ms) the duration of the stimulus. Both duration and amplitude of this long-lasting depolarization were linearly related to train frequency. The train-evoked sustained depolarization was demonstrated to be the result of the additional activation of cholinergic fibers projecting onto PH neurons, because it was prevented by slice superfusion with atropine sulfate and pirenzepine (two cholinergic antagonists), and mimicked by carbachol and McN-A-343 (two cholinergic agonists). These results were confirmed in alert behaving cats. Microinjections of atropine and pirenzepine evoked an ipsilateral gaze-holding deficit consisting of an exponential-like, centripetal eye movement following saccades directed toward the injected site. These findings suggest that the sustained activity present in PH neurons carrying eye-position signals is the result of the combined action of PPRF neurons and the facilitative role of cholinergic terminals, both impinging on PH neurons. The present results are discussed in relation to other proposals regarding integrative properties of PH neurons and/or related neural circuits.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylcholine / metabolism*
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Cholinergic Agents / pharmacology
  • Fixation, Ocular / physiology*
  • Models, Neurological
  • Neural Networks, Computer
  • Neurons / drug effects
  • Neurons / physiology*
  • Receptors, AMPA / physiology
  • Reticular Formation / cytology*
  • Visual Perception / physiology


  • Cholinergic Agents
  • Receptors, AMPA
  • Acetylcholine