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

Abstract

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 IA, 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.

Activity-Dependent Long-Term Potentiation of Intrinsic Excitability in Hippocampal CA1 Pyramidal Neurons

“…The correlation of decrease in the AP threshold with learning-related behavior changes has been established by several groups (Schreurs et al, 1997(Schreurs et al, , 1998Burrell et al, 2001). LTP-IE expressed as a hyperpolarized shift in the activation property of VGSCs in this study adds another piece of evidence to support this important concept.…”

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

“…We propose that a comparative analysis of circuit topography activated by memory recall in normal and aging animals will be useful for understanding the mechanisms of retrieval deficits and that detailed knowledge of brain activity distribution will make the detection of memory underlying neuronal plasticity a more feasible task. Enduring intrinsic and synaptic correlates of recent and long-term memories were detected recently on the basis of the precise knowledge of brain subregions that are critical for memory function (Schreurs et al, 1997(Schreurs et al, , 1998Gusev and Alkon, 2001). We found that the entorhinohippocampal neuronal activity that underlies the recall of recent and remote spatial memories has an anatomically distributed and time-dependent organization throughout the HC.…”

Bidirectional plasticity of excitatory postsynaptic potential (EPSP)-spike coupling in CA1 hippocampal pyramidal neurons

“…These changes in excitability could be implicated in learning and memory because increases in neuronal excitability are reported in hippocampal and cerebellar neurons after classical conditioning (26,27). In invertebrates, bidirectional changes in excitability are induced concomitantly with sensitization and habituation (28).…”