Better Learning Without Channels

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Science  10 Dec 2004:
Vol. 306, Issue 5703, pp. 1863
DOI: 10.1126/science.306.5703.1863c

Nolan et al. conclude that a single type of ion channel can play different roles in learning and memory from their studies of mice lacking the HCN1 protein, a subunit of a channel that accounts for hyperpolarization-activated inward currents. HCN1-knockout mice exhibit motor learning deficits, but mice lacking HCN1 in forebrain neurons actually performed better than wild-type animals on a spatial memory task. Loss of the channel also enhanced long-term memory of how to perform the task. In the CA1 region of the hippocampus, enhanced low-frequency oscillations in neuronal activity were detected in the knockout animals. The pyramidal cells in this region integrate inputs that come from the entorhinal cortex (the perforant pathway) with those from the Schaffer collateral pathway. HCN1 channels are more abundant in the distal dendrites where perforant pathway inputs are localized, and loss of HCN1 preferentially enhanced postsynaptic responses to a single input from the perforant pathway. Similarly long-term potentiation was enhanced at these perforant path synapses. The authors propose that learning may be suppressed by HCN1 channels because they inhibit postsynaptic changes at distal dendrites that would otherwise result in synaptic plasticity. The loss of HCN1 changes the way in which pyramidal cells integrate incoming signals, enhancing responses to low-frequency waveforms and favoring responses to the distal rather than proximal dendrites. This may be particularly important for spatial learning and memory because CA1 pyramidal neurons are thought to compare sensory input from the perforant pathway with stored information from the CA3 region. — LBR

Cell 119, 719 (2004).

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