The Journal of Neurophysiology Vol. 77 No. 1 January 1997, pp. 86-92
Copyright ©1997 The American Physiological Society

Dendritic Excitability Microzones and Occluded Long-Term Depression After Classical Conditioning of the Rabbit's Nictitating Membrane Response

Bernard G. Schreurs, 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, Maryland 20892

Schreurs, Bernard G., Daniel Tomsic, Pavel A. Gusev, and Daniel L. Alkon. Dendritic excitability microzones and occluded long-term depression after classical conditioning of the rabbit's nictitating membrane response. J. Neurophysiol. 77: 86-92, 1997. 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 postsynaptic 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 EPSPs 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 h after classical conditioning. Long-term changes within Purkinje cells that effect this enhanced excitability may occlude pairing-specific long-term depression.

This article has been cited by other articles:

				B. D. Burrell and K. M. Crisp Serotonergic Modulation of Afterhyperpolarization in a Neuron That Contributes to Learning in the Leech J Neurophysiol, February 1, 2008; 99(2): 605 - 616. [Abstract] [Full Text] [PDF]

				B. C. Nolan and J. H. Freeman Purkinje cell loss by OX7-saporin impairs acquisition and extinction of eyeblink conditioning. Learn. Mem., May 1, 2006; 13(3): 359 - 365. [Abstract] [Full Text] [PDF]

				B. D. Burrell and C. L. Sahley Serotonin Mediates Learning-Induced Potentiation of Excitability J Neurophysiol, December 1, 2005; 94(6): 4002 - 4010. [Abstract] [Full Text] [PDF]

				P. A. Gusev, C. Cui, D. L. Alkon, and A. N. Gubin Topography of Arc/Arg3.1 mRNA Expression in the Dorsal and Ventral Hippocampus Induced by Recent and Remote Spatial Memory Recall: Dissociation of CA3 and CA1 Activation J. Neurosci., October 12, 2005; 25(41): 9384 - 9397. [Abstract] [Full Text] [PDF]

				B. Sacchetti, B. Scelfo, and P. Strata The Cerebellum: Synaptic Changes and Fear Conditioning Neuroscientist, June 1, 2005; 11(3): 217 - 227. [Abstract] [PDF]

				J. Xu, N. Kang, L. Jiang, M. Nedergaard, and J. Kang Activity-Dependent Long-Term Potentiation of Intrinsic Excitability in Hippocampal CA1 Pyramidal Neurons J. Neurosci., February 16, 2005; 25(7): 1750 - 1760. [Abstract] [Full Text] [PDF]

				G. Daoudal and D. Debanne Long-Term Plasticity of Intrinsic Excitability: Learning Rules and Mechanisms Learn. Mem., November 1, 2003; 10(6): 456 - 465. [Abstract] [Full Text] [PDF]

				T. Ohyama, W. L. Nores, and M. D. Mauk Stimulus Generalization of Conditioned Eyelid Responses Produced Without Cerebellar Cortex: Implications for Plasticity in the Cerebellar Nuclei Learn. Mem., September 1, 2003; 10(5): 346 - 354. [Abstract] [Full Text] [PDF]

				B. G. Schreurs Classical Conditioning and Modification of the Rabbit's (Oryctolagus Cuniculus) Unconditioned Nictitating Membrane Response Behav Cogn Neurosci Rev, June 1, 2003; 2(2): 83 - 96. [Abstract] [PDF]

				G. Daoudal, Y. Hanada, and D. Debanne Bidirectional plasticity of excitatory postsynaptic potential (EPSP)-spike coupling in CA1 hippocampal pyramidal neurons PNAS, October 29, 2002; 99(22): 14512 - 14517. [Abstract] [Full Text] [PDF]

				M. Ito Cerebellar Long-Term Depression: Characterization, Signal Transduction, and Functional Roles Physiol Rev, July 1, 2001; 81(3): 1143 - 1195. [Abstract] [Full Text] [PDF]

				J. H. Freeman Jr and D. A. Nicholson Developmental Changes in Eye-Blink Conditioning and Neuronal Activity in the Cerebellar Interpositus Nucleus J. Neurosci., January 15, 2000; 20(2): 813 - 819. [Abstract] [Full Text] [PDF]

				B. G. Schreurs, P. A. Gusev, D. Tomsic, D. L. Alkon, and T. Shi Intracellular Correlates of Acquisition and Long-Term Memory of Classical Conditioning in Purkinje Cell Dendrites in Slices of Rabbit Cerebellar Lobule HVI J. Neurosci., July 15, 1998; 18(14): 5498 - 5507. [Abstract] [Full Text] [PDF]

				J W Moore and J S Choi Conditioned response timing and integration in the cerebellum. Learn. Mem., January 1, 1997; 4(1): 116 - 129. [Abstract] [PDF]