Inactivation of presenilins causes pre-synaptic impairment prior to post-synaptic dysfunction
Suedhof, Thomas C.
MetadataShow full item record
Citation (published version)Dawei Zhang, Chen Zhang, Angela Ho, Alfredo Kirkwood, Thomas C Suedhof, Jie Shen. 2010. "Inactivation of presenilins causes pre-synaptic impairment prior to post-synaptic dysfunction." JOURNAL OF NEUROCHEMISTRY, Volume 115, Issue 5, pp. 1215 - 1221 (7). https://doi.org/10.1111/j.1471-4159.2010.07011.x
Synaptic dysfunction is widely thought to be a pathogenic precursor to neurodegeneration in Alzheimer’s disease (AD), and the extent of synaptic loss provides the best correlate for the severity of dementia in AD patients. Presenilins 1 and 2 are the major causative genes of early‐onset familial AD. Conditional inactivation of presenilins in the adult cerebral cortex results in synaptic dysfunction and memory impairment, followed by age‐dependent neurodegeneration. To characterize further the consequence of presenilin inactivation in the synapse, we evaluated the temporal development of pre‐synaptic and post‐synaptic deficits in the Schaeffer‐collateral pathway of presenilin conditional double knockout (PS cDKO) mice prior to onset of neurodegeneration. Following presenilin inactivation at 4 weeks, synaptic facilitation and probability of neurotransmitter release are impaired in PS cDKO mice at 5 weeks of age, whereas post‐synaptic NMDA receptor (NMDAR)‐mediated responses are normal at 5 weeks but impaired at 6 weeks of age. Long‐term potentiation induced by theta burst stimulation is also reduced in PS cDKO mice at 6 weeks of age. These results show that loss of presenilins results in pre‐synaptic deficits in short‐term plasticity and probability of neurotransmitter release prior to post‐synaptic NMDAR dysfunction, raising the possibility that presenilins may regulate post‐synaptic NMDAR function in part via a trans‐synaptic mechanism.
Rights"© 2010 The Authors. Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://www.wileyauthors.com/onlineopen"
Showing items related by title, author, creator and subject.
Pre-synaptic and post-synaptic pathways from the hippocampus to medial prefrontal cortex in Rhesus monkeys Onochie, Ifeanyirochukwu (2017)The hippocampal to medial prefrontal cortex (HPC-mPFC) pathway has a role in mnemonic processing. A key function of the hippocampus (HPC) is to organize contextual memories by how they were experienced, and the prefrontal ...
Frequency-Dependent Synaptic Potentiation, Depression and Spike Timing Induced by Hebbian Pairing in Cortical Pyramidal Neurons Okatan, Murat; Grossberg, Stephen (Boston University Center for Adaptive Systems and Department of Cognitive and Neural Systems, 2000-01)Experiments by Markram and Tsodyks (1996) have suggested that Hebbian pairing in cortical pyramidal neurons potentiates or depresses the transmission of a subsequent presynaptic spike train al steady-state depending on ...