Journal of Neuroscience, Vol 8, 3327-3336, Copyright © 1988 by Society for Neuroscience
Spontaneous and harmaline-stimulated Purkinje cell activity in rats with a genetic movement disorder
SE Stratton, JF Lorden, LE Mays and GA Oltmans
Department of Psychology, University of Alabama, Birmingham 35294.
The genetically dystonic rat (dt) displays a complex movement disorder in
the absence of morphological defects in the nervous system. This mutant is
also insensitive to the tremorogenic effects of harmaline. Because
harmaline is known to act on the cells of the inferior olive to induce
activity at the tremor frequency in the olivocerebellobulbar pathway, this
pathway has been investigated as a possible site of a defect in the dt rat.
Biochemical studies suggested the presence of abnormalities at the level of
the Purkinje cell or its afferent input. Thus, the present study
investigated the harmaline response of Purkinje cells in dt rats and
unaffected littermate controls with extracellular single-unit recording
techniques. The spontaneous, simple spike and complex spike firing rates of
dt rats were significantly lower than those of normal littermate controls.
In normal rats, 2 responses to systemic harmaline injection were seen.
Simple spikes were either completely suppressed for periods of 30-180 min,
or were intermittently suppressed, pausing repeatedly for periods of 1-18
sec. Cells that showed complete suppression of simple spike activity also
showed increased frequency and rhythmicity of complex spikes. In dt rats,
intermittent simple spike responses were seen in a proportion (41%) similar
to that in normal rats (53%). However, the proportion of cells showing
high-frequency, rhythmic, complex spikes and complete suppression of simple
spikes was low in the dt rats in comparison with littermate controls (18
versus 47%). In addition, 41% of the cells from dt rats displayed no
change, or an anomalous change, in firing patterns in response to
harmaline. Since the rhythmic activation of olivary neurons that results in
the rhythmic, complex spike discharge of Purkinje cells is assumed to be
responsible for the appearance of harmaline tremor, the failure of the dt
rat to display tremor is most likely due to a failure at the
olivocerebellar level, rather than at a site efferent to the cerebellum.
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