Effects of target depletion on adult mammalian central neurons: functional correlates.
The physiological signals and patterns of synaptic connectivity that CNS neurons display after the loss of their target cells were evaluated in adult cats for one year. Abducens internuclear neurons were chosen as the experimental model because of their highly specific projection onto the medial rectus motoneurons of the oculomotor nucleus. Selective death of medial rectus motoneurons was induced by the injection into the medial rectus muscle of ricin, a potent cytotoxic lectin that leaves the presynaptic axons intact. The electrical activity of antidromically identified abducens internuclear neurons was recorded in chronic alert animals, during both spontaneous and vestibularly induced eye movements, before and after target removal. During the three weeks that followed ricin injection, abducens internuclear neurons exhibited several firing-related abnormal properties. There was an overall reduction in firing rate with a corresponding increase in the eye position threshold for recruitment. In addition, neuronal sensitivities to eye position and velocity were significantly decreased with respect to control data. Bursting activity was also altered since low-frequency delayed burst accompanied the saccades in the on-direction and, occasionally, internuclear neurons exhibited low-frequency discharges associated with off-directed saccades. Intracellular recordings carried out seven and 15 days after ricin injection demonstrated no significant changes in their electrical properties, although a marked depression of synaptic transmission was evident. The amplitude of both excitatory and inhibitory postsynaptic potentials of vestibular origin was reduced by 60-85% with respect to controls. However, postsynaptic potentials recorded one month after ricin injection showed normal amplitude values which persisted unaltered one year after target loss. Recovery of synaptic transmission occurred at the same time as the re-establishment of normal eye-related signals in the discharge pattern of abducens internuclear neurons recorded in alert cats from days 25-30 post lesion. The functional restoration of firing properties was maintained in the long term (one year). Conversely, abducens motoneurons showed normal firing and synaptic patterns at all time intervals analysed. These results demonstrate that, after an initial period of altered physiological properties, abducens internuclear neurons survive the loss of their target motoneurons and regain a normal discharge pattern and afferent synaptic connections.
de la Cruz
R R
RR
Departamento de Fisiología y Biología Animal, Facultad de Biología, Universidad de Sevilla, Spain.
Pastor
A M
AM
Delgado-García
J M
JM
D000010:Abducens Nerve / Q000503:physiopathology*; D000200:Action Potentials; D000818:Animals; D001370:Axonal Transport; D001369:Axons; D001933:Brain Stem / Q000503:physiopathology; D002415:Cats; D005260:Female; D005403:Fixation, Ocular / Q000502:physiology; D007273:Injections, Intramuscular; D009046:Motor Neurons / Q000502:physiology; D009801:Oculomotor Muscles / Q000294:innervation*; D012183:Retrograde Degeneration; D012276:Ricin / Q000008:administration & dosage / Q000633:toxicity; D012438:Saccades / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
D012276:Ricin