Dendritic Excitability Microzones and Occluded Long-Term Depression After
Classical Conditioning of the Rabbit's Nictitating Membrane Response.
Schreurs, Bernard G., Daniel Tomsic, Pavel A. Gusev and Daniel L. Alkon.
Laboratory of Adaptive Systems, National Institute of Neurological
Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
APStracts 3:0208N, 1996.
We made intradendritic recordings in Purkinje cells (n=164) from parasaggital
slices of cerebellar lobule HVI obtained from rabbits given paired
presentations of tone and periorbital electrical stimulation (classical
conditioning, n=27) or explicitly unpaired presentations of tone and
periorbital stimulation (control, n=16). Purkinje cell dendritic membrane
excitability, assessed by the current required to elicit local dendritic
calcium spikes, increased significantly in slices from animals that received
classical conditioning. In contrast, membrane potential, input resistance and
amplitude of somatic and dendritic spikes were not different in slices from
animals given paired or explicitly unpaired stimulus presentations. The
location of cells with low thresholds for local dendritic calcium spikes
suggested that there are specific sites for learning-related changes within
lobule HVI. These areas may correspond to learning "microzones" and are
consistent with locations of learning related in vivo changes in Purkinje cell
activity. Application of 4-aminopyridine, an antagonist of the rapidly
inactivating potassium current I A , reduced the threshold for dendritic
spikes in slices from naive animals to levels found in slices from trained
animals. In cells where thresholds for eliciting parallel fiber-stimulated
Purkinje cell excitatory post synaptic potentials (EPSPs) were measured,
levels of parallel fiber stimulation required to elicit a 6-mV EPSP as well as
a 4-mV EPSP (n=30) and a Purkinje cell spike (n=56) were found to be
significantly lower in slices from paired animals than unpaired controls. A
classical conditioning procedure was simulated in slices of lobule HVI by
pairing a brief, high frequency train of parallel fiber stimulation (8 pulses,
100 Hz) with a brief, lower frequency train of climbing fiber stimulation (3
pulses, 20 Hz) to the same Purkinje cell. Following paired stimulation of the
parallel and climbing fibers, Purkinje cell excitatory post synaptic
potentials underwent a long-term (> 20 min) reduction in peak amplitude (-24%)
in cells (n=12) from animals given unpaired stimulus presentations but to a
far less extent (-9%) in cells (n=20) from animals given in vivo paired
training. Whereas 92% of cells from unpaired animals showed pairing-specific
depression, 50% of cells from paired animals showed no depression and in
several cases showed potentiation. Our data establish that there are localized
learning-specific changes in membrane and synaptic excitability of Purkinje
cells in rabbit lobule HVI that can be detected in slices 24 hours after
classical conditioning. Long-term changes within Purkinje cells that effect
this enhanced excitability may occlude pairing-specific long-term depression.
Received 11 July 1996; accepted in final form 9 September 1996.
APS Manuscript Number J546-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996