{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T09:56:00Z","timestamp":1772963760167,"version":"3.50.1"},"reference-count":42,"publisher":"Society for Neuroscience","issue":"45","license":[{"start":{"date-parts":[[2012,5,9]],"date-time":"2012-05-09T00:00:00Z","timestamp":1336521600000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2011,11,9]]},"abstract":"<jats:p>Current therapies for Alzheimer's disease (AD) address a loss of cholinergic neurons, while accumulation of neurotoxic amyloid \u03b2 (A\u03b2) peptide assemblies is thought central to molecular pathogenesis. Overlaps may exist between prionopathies and AD wherein A\u03b2 oligomers bind to the cellular prion protein PrP<jats:sup>C<\/jats:sup>and inhibit synaptic plasticity in the hippocampus (Laur\u00e9n et al., 2009). Here we applied oligomeric A\u03b2 to neurons with different PrP (<jats:italic>Prnp<\/jats:italic>) gene dosage. Whole-cell recordings were obtained from dissociated neurons of the diagonal band of Broca (DBB), a cholinergic basal forebrain nucleus. In wild-type (wt) mice, A\u03b2<jats:sub>1\u201342<\/jats:sub>evoked a concentration-dependent reduction of whole-cell outward currents in a voltage range between \u221230 and +30 mV; reduction occurred through a combined modulation of a suite of potassium conductances including the delayed rectifier (<jats:italic>I<\/jats:italic><jats:sub>K<\/jats:sub>), the transient outward (<jats:italic>I<\/jats:italic><jats:sub>A<\/jats:sub>), and the iberiotoxin-sensitive (calcium-activated potassium,<jats:italic>I<\/jats:italic><jats:sub>C<\/jats:sub>) currents. Inhibition was not seen with A\u03b2<jats:sub>42\u20131<\/jats:sub>peptide, while A\u03b2<jats:sub>1\u201342<\/jats:sub>-induced responses were reduced by application of anti-PrP antibody, attenuated in cells from<jats:italic>Prnp<\/jats:italic><jats:sup>0\/+<\/jats:sup>hemizygotes, and absent in<jats:italic>Prnp<\/jats:italic><jats:sup>0\/0<\/jats:sup>homozygotes. Similarly, amyloidogenic amylin peptide depressed DBB whole-cell currents in DBB cells from wt mice, but not<jats:italic>Prnp<\/jats:italic><jats:sup>0\/0<\/jats:sup>homozygotes. While prior studies give broad support for a neuroprotective function for PrP<jats:sup>C<\/jats:sup>, our data define a latent pro-pathogenic role in the presence of amyloid assemblies.<\/jats:p>","DOI":"10.1523\/jneurosci.4367-11.2011","type":"journal-article","created":{"date-parts":[[2011,11,9]],"date-time":"2011-11-09T17:51:06Z","timestamp":1320861066000},"page":"16292-16297","source":"Crossref","is-referenced-by-count":30,"title":["A\u03b2 Inhibition of Ionic Conductance in Mouse Basal Forebrain Neurons Is Dependent upon the Cellular Prion Protein PrP<sup>C<\/sup>"],"prefix":"10.1523","volume":"31","author":[{"given":"Kwai","family":"Alier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Westaway","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack H.","family":"Jhamandas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"393","published-online":{"date-parts":[[2011,11,9]]},"reference":[{"key":"2023041303533181000_31.45.16292.1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22372"},{"key":"2023041303533181000_31.45.16292.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.04.031"},{"key":"2023041303533181000_31.45.16292.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911829107"},{"key":"2023041303533181000_31.45.16292.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6500-10.2011"},{"key":"2023041303533181000_31.45.16292.5","doi-asserted-by":"crossref","unstructured":"Bate C Williams A (2011) Amyloid-{beta}-induced synapse damage is mediated via cross-linkage of the cellular prion protein. 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