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Received November 7, 2006
Revised November 22, 2006
Accepted after revision November 22, 2006
1 Northwestern University Feinberg School of Medicine
2 Northwestern University Feinberg Medical School
3 Northwestern University
* To whom correspondence should be addressed. E-mail: c-kaczorowski{at}northwestern.edu.
CA1 pyramidal neurons from animals that have acquired a hippocampus-dependent task show increased neuronal excitability, as evidenced by a reduction in the post-burst afterhyperpolarization (AHP). Studies of AHP plasticity require stable long-term recordings, which are affected by the intracellular solutions potassium methylsulfate (KMeth) or potassium gluconate (KGluc). Here we show immediate and gradual effects of these intracellular solutions on measurement of the AHP and basic membrane properties, and on the induction of AHP plasticity in CA1 pyramidal neurons from rat hippocampal slices. The AHP measured immediately after establishing whole-cell recordings was larger with KMeth than with KGluc. In general, the AHP in KMeth was comparable to the AHP measured in perforated-patch configuration. However, KMeth induced time-dependent changes in the intrinsic membrane properties of CA1 pyramidal neurons. Specifically, input resistance (RN) progressively increased by 70% after 50 minutes; correspondingly, the current required to trigger an action potential (Ithreshold) and the fast afterdepolarization (fADP) following action potentials gradually decreased by about 50%. Conversely, these measures were stable in KGluc. We also demonstrate that activity-dependent plasticity of the AHP occurs with physiologically relevant stimuli in KGluc. AHPs triggered with theta-burst firing every 30 seconds were progressively reduced, whereas AHPs elicited every 150 seconds were stable. Blockade of the apamin-sensitive AHP (IAHP) was insufficient to block AHP plasticity, suggesting plasticity is manifested through changes in the apamin-insensitive sIAHP. These changes were observed in the presence of synaptic blockers, and therefore reflect changes in the intrinsic properties of the neurons. However, no AHP plasticity was observed using KMeth. In summary, these data show that KMeth produces a time-dependent change in basic membrane properties and prevents or obscures activity-dependent reduction of the AHP. In whole-cell recordings using KGluc, repetitive theta-burst firing induced AHP plasticity that closely mimics the learning-related reduction in the AHP.
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