Post by Admin on Feb 3, 2019 11:44:29 GMT
Amyloid-beta inhibits E-S Potentiation through suppression of cannabinoid receptor 1-dependent synaptic disinhibition
Summary
It has been widely reported that β-amyloid peptide (Aβ) blocks long-term potentiation (LTP) of hippocampal synapses. Here we show evidence that Aβ more potently blocks the potentiation of excitatory post-synaptic potential (EPSP) -spike coupling (E-S potentiation). This occurs not by direct effect on excitatory synapses or postsynaptic neurons, but rather through a novel indirect mechanism: reduction of endocannabinoid-mediated peri-tetanic disinhibition. During high frequency (tetanic) stimulation, somatic synaptic inhibition is suppressed by endocannabinoids. We find that Aβ prevents this endocannabinoid-mediated disinhibition, thus leaving synaptic inhibition more intact during tetanic stimulation. This intact inhibition opposes the normal depolarization of hippocampal pyramidal neurons that occurs during tetanus, thus opposing the induction of synaptic plasticity. Thus, a novel pathway through which Aβ can act to modulate neural activity is identified, relevant to learning and memory and how it may mediate aspects of the cognitive decline seen in Alzheimer's disease.
Source www.ncbi.nlm.nih.gov/pmc/articles/PMC4114400/
Summary
It has been widely reported that β-amyloid peptide (Aβ) blocks long-term potentiation (LTP) of hippocampal synapses. Here we show evidence that Aβ more potently blocks the potentiation of excitatory post-synaptic potential (EPSP) -spike coupling (E-S potentiation). This occurs not by direct effect on excitatory synapses or postsynaptic neurons, but rather through a novel indirect mechanism: reduction of endocannabinoid-mediated peri-tetanic disinhibition. During high frequency (tetanic) stimulation, somatic synaptic inhibition is suppressed by endocannabinoids. We find that Aβ prevents this endocannabinoid-mediated disinhibition, thus leaving synaptic inhibition more intact during tetanic stimulation. This intact inhibition opposes the normal depolarization of hippocampal pyramidal neurons that occurs during tetanus, thus opposing the induction of synaptic plasticity. Thus, a novel pathway through which Aβ can act to modulate neural activity is identified, relevant to learning and memory and how it may mediate aspects of the cognitive decline seen in Alzheimer's disease.
Source www.ncbi.nlm.nih.gov/pmc/articles/PMC4114400/