Repository logo
 

The amnestic agent anisomycin disrupts intrinsic membrane properties of hippocampal neurons via a loss of cellular energetics

Simple item page
dc.contributor.authorScavuzzo, C. J.
dc.contributor.authorLeBlancq, M. J.
dc.contributor.authorNargang, F.
dc.contributor.authorLemieux, H.
dc.contributor.authorHamilton, Trevor
dc.contributor.authorDickson, C. T.
dc.date.accessioned2020-10-15
dc.date.accessioned2022-05-31T01:15:46Z
dc.date.available2022-05-31T01:15:46Z
dc.date.issued2019
dc.description.abstractThe nearly axiomatic idea that de novo protein synthesis is necessary for long-term memory consolidation is based heavily on behavioral studies using translational inhibitors such as anisomycin. Although inhibiting protein synthesis has been shown to disrupt the expression of memory, translational inhibitors also have been found to profoundly disrupt basic neurobiological functions, including the suppression of ongoing neural activity in vivo. In the present study, using transverse hippocampal brain slices, we monitored the passive and active membrane properties of hippocampal CA1 pyramidal neurons using intracellular whole cell recordings during a brief ~30-min exposure to fast-bath-perfused anisomycin. Anisomycin suppressed protein synthesis to 46% of control levels as measured using incorporation of radiolabeled amino acids and autoradiography. During its application, anisomycin caused a significant depolarization of the membrane potential, without any changes in apparent input resistance or membrane time constant. Anisomycin-treated neurons also showed significant decreases in firing frequencies and spike amplitudes, and showed increases in spike width across spike trains, without changes in spike threshold. Because these changes indicated a loss of cellular energetics contributing to maintenance of ionic gradients across the membrane, we confirmed that anisomycin impaired mitochondrial function by reduced staining with 2,3,5-triphenyltetrazolium chloride and also impaired cytochrome c oxidase (complex IV) activity as indicated through high-resolution respirometry. These findings emphasize that anisomycin-induced alterations in neural activity and metabolism are a likely consequence of cell-wide translational inhibition. Critical reevaluation of studies using translational inhibitors to promote the protein synthesis dependent idea of long-term memory is absolutely necessary. NEW & NOTEWORTHY Memory consolidation is thought to be dependent on the synthesis of new proteins because translational inhibitors produce amnesia when administered just after learning. However, these agents also disrupt basic neurobiological functions. We show that blocking protein synthesis disrupts basic membrane properties of hippocampal neurons that correspond to induced disruptions of mitochondrial function. It is likely that translational inhibitors cause amnesia through their disruption of neural activity as a result of dysfunction of intracellular energetics.
dc.description.urihttps://library.macewan.ca/full-record/edswsc/000491468500005
dc.identifier.citationScavuzzo C, LeBlancq S, Nargang F, Lemieux H, Hamilton TJ, Dickson CT. (2019). The amnestic agent anisomycin disrupts intrinsic membrane properties of hippocampal neurons via a loss of cellular energetics. Journal of Neurophysiology. doi.org/10.1152/jn.00370.2019
dc.identifier.doihttps://doi.org/10.1152/jn.00370.2019
dc.identifier.urihttps://hdl.handle.net/20.500.14078/1894
dc.languageEnglish
dc.language.isoen
dc.rightsAll Rights Reserved
dc.subjectCA1
dc.subjectcytochrome oxidase
dc.subjectmitochondria
dc.subjectneurosilencing
dc.subjecttranslational inhibition
dc.titleThe amnestic agent anisomycin disrupts intrinsic membrane properties of hippocampal neurons via a loss of cellular energeticsen
dc.typeArticle

Files

Collections

Department of Psychology